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Reticence Around Unveiling Clinical Trials

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While scanning through various publications, we now get to know, almost at regular intervals, about new clinical trials capturing the newer ways of treating different ailments. Such information instils an invigorating hope in the minds of doctors and the patients alike, to more successfully and predictably fight the battle against diseases in the ongoing pursuit for a better quality of life.

However, for independent and impartial assessment of any new drug before it comes to the market, an ethical and transparent process of unveiling clinical trials, sans any reticence whatsoever, are absolutely essential. Only this process would be able to satisfactorily establish, beyond an iota of doubt, the safety and efficacy levels of, especially, the new drugs. To move in that direction, the fundamental requirements will be diligently recording and publishing all types of data – positive, not so positive, and also negative, arising out of all clinical trials, conducted anywhere in the world, for the same drug.

Thus, there should be a system of open access to all clinical trial data, as each trial is completed. Otherwise, pharma companies’ publication bias, overwhelmingly on positive results, would continue, as alleged by many across the world. It is worth noting that over 60 percent of all clinical trials for new drugs are sponsored by the pharma and biotech companies.

There isn’t any dearth of examples of new drugs’ getting not just the required regulatory approval, riding on the back of robust ‘positive’ clinical trial data on safety and efficacy, but also becoming highly dependable money-spinners for the companies, and in no time, as it were. These cash churning new brands would also get well protected for monopolistic pricing all through their respective patent life, and sometimes even after that, in various different ways.

Nevertheless, at a later date, mostly post patent expiry, not all pre-launch new drug trials could be universally accepted as robust and conclusive, especially on their efficacy and safety claims. On the contrary, a number of detailed and deep-stick independent studies indicate that some new drugs are, in fact, much less effective, if not ineffective, and cause more serious side effects than what were published earlier.

Hence, some critical questions are now being asked by many stakeholders, with greater assertiveness than ever before and backed by solid evidence, in this arena. Although it has now started creating a snowballing effect, still, nothing much seems to have changed on the ground, just yet.

Why aren’t all clinical trial results, and for all new drugs not still published, or otherwise made available for public scrutiny, unveiled, and of course after protecting any reasonable commercial interest? Does business consideration, then continue to prevail over the need for transparency in clinical trial data disclosure for patients’ health and safety? The sneaking fear behind the reasons of this reticence of pharma players, in general, continues to torment many. I shall discuss this point in this article backed by recently published data.

Not a recent trend:

This isn’t a recent trend either, and continuing for decades, without any effective remedial measures by the appropriate authorities. I would give just a couple of examples, one from 1998 and the other from 2014, to drive home this point.

A  British Journal of Clinical Pharmacology (BJCP) article, published way back in August 1998 would vindicate this point. This study revealed the following on clinical trial data:

“Substantial evidence of selective reporting was detected, since trials with positive outcome resulted more often in submission of final report to regulatory authorities than those with inconclusive or negative outcomes.”

Another study published on September 10, 2014 in the Journal of American Medical Association (JAMA) states as follows:

“Thirty-five percent of published reanalysis led to changes in the findings that implied conclusions different from those of the original article about the types and number of patients who should be treated.”

That said, I shall now focus on a very recent controversy in this area, related to a blockbuster drug that has now gone off-patent.

A contemporary example:

Statin class of drugs, especially, Atorvastatin is one of many such examples.

Pfizer launched Atorvastatin with the brand name Lipitor in early 1997. At that time, it was the fifth in the statin class of drugs for the treatment of hyperlipidemia.

It was launched on the back of a 1996 clinical study that concluded, Lipitor reduces bad cholesterol significantly more than the other statins, from the very onset of treatment to as long as the treatment continues. After that it’s a history in the pharma industry, Pfizer marketing turned it into the best-selling drug ever, in the history of pharmaceuticals, so far.

Over 14.5 years, Lipitor reportedly made over US$ 125 billion in sales, and provided up to a quarter of Pfizer Inc.’s annual revenue for years.

Product claim – then:

Claiming that in ‘one year alone, statins reduced numerous cases of cardiovascular-related complications and saved thousands of lives’, a Pfizer Paper on “The Value of Statin”, reiterated the drug’s role both in the treatment and prevention of Coronary Artery Diseases (CAD). I am quoting below from this paper to cite just one example each – treatment and prevention:

  • In a study of patients with Coronary Artery Disease (CAD) statin therapy reduced the relative risk of mortality by 50 percent in those > 80-years-old, 44 percent in those 65- to 79-years-old, and 30% in those < 65 years old, compared to CAD patients in the same age group not taking statin therapy (Ref. Chloe, Allen A., et al. ‘Statin Therapy Is Associated With Reduced Mortality Across All Age Groups of Individuals With Significant Coronary Disease, Including Very Elderly Patients’. JACC. 40: 10; 1777-1785)
  • An analysis of 18 trials, including 56,934 patients, primarily without CVD, demonstrated statins conferred a relative risk reduction (RRR) in all-cause mortality by 14 percent and stroke by 22 percent (Ref. Statins for the primary prevention of cardiovascular disease. Cochrane Database System Review. 2013 Jan 31; 1:CD004816).

Research findings for the same drug – now:

Among several other publications on statins, a July 26, 2015 article, published in the ‘World Journal of Cardiology’ concludes as follows:

“History has proven otherwise, and the global prevalence of Coronary Heart Disease (CHD), despite worldwide statin usage and cholesterol lowering campaigns, has reached pandemic proportions. Coronary heart disease is an extremely complex malady and the expectation that it could be prevented or eliminated by simply reducing cholesterol appears unfounded. After twenty years we should concede the anomalies of the cholesterol hypothesis and refocus our efforts on the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD.”

To give one more example, let me quote from a contemporary study, published on June 12, 2016 in the ‘BMJ Open’, which also comes to a similar conclusion, as follows:

“High LDL-C (Low-Density Lipoproteins – Cholesterol) is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (i.e., that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.”

Examples of other drugs:

Lipitor should not stand out as a solitary example, in this field. To establish this point, let me now put forth, just as illustrations, a few more examples of similar bias on positive results in clinical trial publications, besides many others.

An October 4, 2016 article titled, “Big Pharma’s Role in Clinical Trials”, published in the ‘Drug Watch’, quotes several other companies sailing in the same boat, as follows:

  • The Cochrane Collaboration, a nonprofit organization based in London that reviews health care information, concluded that unlike its promotional claims, Roche’s Tamiflu only shortened symptoms of influenza by one day, and it did not prevent hospitalizations or complications from influenza.
  • AstraZeneca reportedly paid US$ 647 million in lawsuit settlements for failing to inform the public of Seroquel’s side effects.
  • Takeda Pharmaceuticals reportedly settled lawsuits claiming the company’s anti-diabetic drug Actos caused bladder cancer, for US$ 2.37 billion.
  • In July 2012, GlaxoSmithKline reportedly pleaded guilty and agreed to pay US$ 3 billion to settle charges brought by the U.S. Department of Justice for failing to report clinical data on its anti-diabetic drug Avandia.
  • Johnson & Johnson was reportedly accused of hiding some dangerous side effects like, diabetes, substantial weight gain, stroke and gynecomastia – or breast development in boys for its product Risperdal – used to treat schizophrenia and bipolar disorder in adults and adolescents and autism spectrum disorders in children and adolescents.  The company reportedly settled claims in Kentucky, Texas and Montana for a total of more than US$ 340 million and settled multiple cases in Pennsylvania for undisclosed amounts.
  • As reported by ‘Financial Times’ on February 03, 2015, Novartis was accused of manipulating trial data in favor of its anti-hypertensive drug – Diovan, and concealing side-effects associated with its Tasigna – for leukemia treatment. As a result, the company reportedly faced a temporary suspension of its business in Japan, as punishment for alleged manipulation of clinical trial data.

Possible reasons:

The above ‘Drug Watch’ article attributed several reasons to positive data bias in publications, as follows:

  • Researchers publish positive findings more often than negative findings as a result of human bias. Scholars want their work to contribute to medical advancement and not deter it.
  • Researchers do not want to put their time and energy into writing studies about negative results.
  • Journals seek positive results, and publish them more quickly to increase publicity.
  • Trial sponsors want to publish positive results to increase profit.

The article emphasized, “Big Pharma funds 60 percent of all clinical trials, and takes advantage of its power to persuade researchers and influence institutions.  The result is an under-informed, and misinformed medical community giving advice to patients with false or incomplete data. The byproducts of industry cover-ups are scores of deaths and millions of dollars in industry profits.”

Indian scenario:

India is also not immune from such alleged wrongdoings. Indian clinical trial organizations have also been accused of trial related scams, and that too on a mega scale, reaching beyond the shores of the country. I am quoting below two such recent examples:

  • In August 2015, the European Union reportedly banned the marketing of around 700 generic medicines for alleged manipulation of clinical trials conducted by the domestic research company GVK Biosciences. This was reported as the largest EU-wide suspension of sales and distribution of generic drugs ordered by the European Commission that was applicable to all its 28 member nations.
  • In July 2016, the European Medicines Agency (EMA) reportedly recommended suspending the sale of dozens of generic medicines over concerns about “flawed” studies that were conducted by the Semler Research Center, located in Bengaluru. Many of these drugs are sold by Novartis and Teva Pharmaceuticals.
  • In September-October 2015, US-FDA also found “significant instances of misconduct and violations of federal regulations by the same research center, which includes substitution and manipulation of study subject samples.”
  • This year, the World Health Organization (WHO) also had issued a notice to Semler for the same reasons. After, examining the company’s computer servers, early and late last year, WHO reportedly found a spreadsheet file containing detailed instructions for manipulating drug samples that were used in clinical trials for its clients. 

It is even more unfortunate that such malpractices are continuing, even after the Supreme Court of India’s widely reported observation in early 2013 that ‘Uncontrolled clinical trials are causing havoc to human life.’ The apex court of the country made this remark in response to a petition filed by the human rights group Swasthya Adhikar Manch (SAM).  

The upshot:

Recent scrutiny of all original clinical trial findings of many new drugs by the independent experts, including statins, even if taken just as raising controversies, the question would still remain, why did such controversies not surface much earlier, or during the product patent life? No company would possibly be willing to unveil the fact behind this raging debate.

The good news is, pharma companies operating in Europe and the United States have decided to share trial data with qualified researchers, effective 2014, presumably in response to mounting pressure from clinical trial transparency campaigners, for quite some time.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA) have jointly released a set of principles detailing plans to allow greater access to information from clinical trials. However, it fell short of public availability of all clinical trial data. Let’s wait, watch and hope that this seemingly good intent would be translated into reality by all their member companies.

Some pharma companies and their trade associations continue to raise issues of the various legalities against related to public disclosures of all trial data. Nevertheless, it is worth noting that in April 2014, a legislation was approved in Europe by the European Parliament to increase transparency in clinical trials by making the trial results publicly available. EMA was commissioned by the European Parliament to create a database where all interested parties could view comprehensive data from clinical trials. The transparency rules for the European Clinical Trial Regulation entered into force on January 1, 2015 and apply to clinical trial reports contained in all marketing authorization applications submitted on or after this date. On March 3, 2016, EMA announced the detailed guidance on the requirements for pharmaceutical companies to comply with the agency’s policy on publication of clinical trials data for all medicines. Chapter Three of this publication gives guidance to companies on how to anonymize clinical reports for the purpose of publication.

The EMA initiative of transparency of clinical trial data  aims at ensuring that drug companies are aware of what is expected of them, and that they are ready for the publication of these critical data.

Besides Europe, in the United States too, though there is a clear mandate of the federal government that all clinical trial results related to serious or life-threatening diseases require to be published and uploaded on ClinicalTrials.gov – the database of the Government covering all clinical trials in America. However, this government mandate also seems to be hardly followed, both in its letter and spirit, according to reports. Similar scenario, reportedly, still prevails in most other developed countries, as well. India does not seem to be any different in this matter, either.

Intriguingly, the whole issue continues to remain polemical, with more number of initial clinical trial conclusions reportedly turning out to be not as transparent as these ought to be, carrying a significant bias towards positive treatment outcomes.

As a result, prevailing reticence around unveiling all clinical trials, including those of blockbuster drugs, is eventually pushing many patients to the brink of much avoidable and unforeseen serious health risk.

By: Tapan J. Ray  

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion. 

An Evolving Paradigm of ‘Price-Value Model’ Of Pharma Value Delivery System

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May 4, 2016 edition of the ‘MIT Technology Review’ published an interesting article carrying the headline, “The World’s Most Expensive Medicine Is a Bust”.

The obvious question that floats at the top of mind: What is this most expensive drug in the pharma history, and why has it failed commercially, despite being a product of disruptive innovation and a marvel that stands out in the space of contemporary drug innovation? 

The product is called Glybera (alipogene tiparvovec). It heralded the dawn of the “first gene therapy” in the Western world, whose approval helped ignite an explosion of investment and excitement around treatments that correct DNA, as the MIT article said.  

Glybera promises to cure rare inherited diseases with one-time repairs to a person’s DNA. A single dose of gene therapy can change the genetic instructions inside a person’s cells in ways that last many years, or even a lifetime. 

Interestingly, even with this unprecedented product offering, the product has become a commercial flop, due to its staggering million-dollar price tag, which very few patients can afford.

Is this an extreme example of price-value relationship for a new breakthrough pharma product? Yes, of course!  Nevertheless, it makes us ponder on some key fundamentals, afresh, such as:

  • The core purpose of drug innovation
  • The price-value relationship of even breakthrough drugs

The proper understanding of these points comprehensively, especially the above two fundamentals, would enable the drug companies to achieve both, the core purpose of intricate drug innovation initiatives, and also making these medicines commercially successful with increased access to patients, through innovative ‘value delivery’ mechanisms.

I believe, the pharmaceutical industry is now at the threshold of a paradigm shift. The new paradigm would signal a metamorphosis in the price-value equations for all drugs, mostly due to changing socio-political environment, across the world, as we have started witnessing in the topmost free economy of the world – the United States.

Pharma business is a ‘value delivery system’: 

Way back in June 2000, an article published in ‘McKinsey Quarterly’ on delivering value to the customers, deliberated on a 1988 paper of Michael J. Lanning and Edward G. Michaels. The study combines the value-maps developed in the price-value models with the idea of the “business system,” which was introduced in 1980.

The paper titled, “A business is a value delivery system,” emphasizes the importance of a clear, well-articulated “value proposition” for each targeted market segment. This means a simple statement of the benefits that the company intends to provide to each segment, along with the approximate price the company will charge each segment for those benefits. 

Looking at this concept in pharma perspective:

Keeping the above paper in perspective, when we look at the pharma value delivery system, besides the key benefits that a drug offers, one of the most critical value parameter continues to be the financial value.

The healthcare value chain, across the world, has started sharpening its focus on the drug cost today, more than ever before. This is primarily based on the differential value that a drug offers as compared to its closest alternatives. We may like it or not, it is happening irrespective of, whether the drug in question is a breakthrough innovation, or an off-patent high-priced generic medicine.

As I said before, not just in India, the affordability of health care in general, and medicines in particular, is rapidly emerging as a key concern for all developed and the developing nations, including the United States.

Thus, even after careful consideration of all novel product’s benefits and the costs associated with these, the stakeholders’ focus is getting sharper on the overall financial value of the product offerings to the patients. This is reality, and can’t just be wished away by any measure of powerful and expensive advocacy campaigns, together with clever media management. 

The drug companies may continue to crib about it, but this will possibly lead them nowhere, in the long term. Instead, they would require to search for a workable win-win and level headed solution, for this most fundamental business issue.

Understanding the evolving paradigm:

We are fast arriving at this new paradigm. There, the financial value of a drug, in the ‘value delivery system’ of pharma marketing, would occupy the center stage. The drug companies would need to arrive at this financial value, not just by understanding the professional mindset of the doctors and taking them on board somehow, but by properly understanding what would the majority of stakeholders want to pay for a new drug, and then perhaps work backwards to translate that finding into reality. 

Its successful application would soon assume a pivotal role in the pharma value delivery system. A company may contemplate pricing a drug high, limiting its access to a few rich, and still succeed in making its cash register ringing, such as, some new hepatitis C or cancer drugs. Nonetheless, this could ultimately make their overall business socio-politically too vulnerable, and may not be sustainable either, in the long run. 

The same old and current approach does not create a wholesome value for a new drug to most of the customers, despite the company having a state of art ‘value delivery platform’, for unleashing a dazzling marketing blitzkrieg.                                 

The pharma marketing strategy remains unchanged and stale: 

At a time, when a paradigm shift is taking place, especially in the way the entire world views at the price-value equation of a new drug, the overall strategic approach of the pharma marketers, as I see it, still remains in the old paradigm, with its roots firmly entrenched there.

I think it so, because the traditional pharma marketing has always been a unilateral communication process, predominantly involving the doctors, and trying to fathom their needs, wants and professional mindset.

Accordingly, the product value delivery process for the doctors, with or without the medical representatives, is basically woven around those needs, wants and mindsets of the target doctors. It, by and large, continues even today, with some cosmetic changes in tools and formats here or there. 

Therefore, when the basic marketing and communication process aims at effectively delivering the value of drugs, let us discuss briefly what does the core value of a drug mean?

The value of a drug: 

For this purpose, I reckon, it would be prudent to avoid an ethereal approach to arrive at the financial value of a drug, such as, what is the cost of a life, as often raised by many pharma players. A practical approach to resolve this issue would benefit all, in every way.

Without going much into the core purpose of pharma innovation, usually the drug companies define the value of a medicine based on what they think about its attributes. Accordingly, respective players arrive at its financial value, that the patients or the payers must pay for, if they want to have an access to it. 

Usually not many independent studies are conducted by the drug companies to ascertain how much the majority of stakeholders, including the governments, payers and patients, would want to willingly pay for a new drug, after well considering its value offerings.

Competitive Scenario:

The ever increasing, and virtually obsessed focus on drug ‘innovation’, while justifying the high financial value of a medicine for the patients, also restricts competition, especially for newer ones. For most of the patients this situation is a double whammy.

Additionally, the consolidation process within the industry is also fuelling this situation further. The virtual monopoly of a few companies with some new drugs, in key therapy segments, such as, diabetes, cancer, vaccines and HIV, is restricting the overall competitive environment. This would continue.

A September 24, 2014 Article, published in the ‘Insight’ of Bain & Company on the throws some light on the subject. It says, “over the past 20 years, and especially since 2000, building leadership in a category has become a crucial route to success in pharma. Seven of our 10 leading value creators, including Roche in oncology and Novo Nordisk in diabetes care, generated at least 50 percent of their revenues from one therapeutic area or primary care. In two cases – Biogen Idec in neurology and Celgene in oncology – more than 90 percent of revenues came from a single therapeutic area.”

As I said, this process is expected to continue, it is necessary for the drug companies, governments, other payers and the patients understand the new paradigm, and act accordingly to address this issue to protect mutual benefit.

If it does not happen, the evolving socio-political environment, across the world, would occupy the driver’s seat to navigate through this complexity, in the healthcare space in general and pharma in particular, safeguarding the patients’ health interest. 

The core issue:

In the prevailing scenario, the core issue that gets reinforced, yet again, as raised by many, including the World Health Organization (WHO), is the growing inherent conflict between predominantly the profit driven business goals of the pharma players, and the public health interest of a nation.

Possibly for this reason, Dr. Margaret Chan, the Director General of the World Health Organization (WHO), at a briefing to discuss the Ebola outbreak in West Africa at the UN Foundation in Washington on September 3, 2014 said:

“Big Pharma’s greed for profits, not lack of funding, delaying Ebola treatment development.” 

Many countries are now seriously striving to arrive at a middle path to resolve this perennial conflict, India included. The drug companies may wish to take note of it.

I discussed this issue in an article published in this Website titled, “Is The Core Purpose of Pharma Business Beyond Profit Making?” on November 10, 2014.

Conclusion:

As the above ‘McKinsey Quarterly’ paper articulated, the strength of the buying proposition for any customer is a function of the product value minus the price. In other words, the ‘surplus value’ that the customer will enjoy once that product is paid for. As the paper clarified, the “value” in a price-value map will necessarily be informed guesses, though after well-considering multiple variables.

Delivering more of this ‘surplus value’ to patients, willy-nilly, would soon be the name of the game, especially for the winners in both the global and local pharma industry. 

In the entire drug sector, including India, this ‘price-value model’ could help a pharma company ascertain the sustainability of its competitive position, well considering the stakeholders’ perspective, and accordingly take the right business decision.

Thus, proper understanding of the ‘surplus value model’ while pricing a drug, and its immaculate execution through state of the art marketing and communication strategies, will separate the men from the boys, for sustained excellence in the pharma business.

Sans understanding of this ‘price-value model’, which is so important in the evolving new paradigm of a pharma value delivery system, a pharma player would risk getting caught in a tough headwind, especially with new high-priced products. This situation could, in turn, jeopardize its long term success, and even erode the well-earned company reputation, in tandem, at times mercilessly.

By: Tapan J. Ray 

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

The Curious Conundrum of New Drugs Approval Process

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Fathoming the details of just a short span of time, not going beyond the last 10 years, I find from the published data that many new drugs, such as, Alatrofloxacin, Aprotinin, Drotrecogin alfa, Lumiracoxib, Propoxyphene, Rofecoxib, Rosiglitazone, Sibutramine, Tegaserod, Tetrazepam, were withdrawn from a number of important global markets. Quite a few of those were withdrawn also from the world market.

The key reason for almost all these withdrawals was serious safety concerns for the patients while using these medicines. Interestingly, some of these new molecules were withdrawn even after attaining the blockbuster status, such as Rofecoxib.

Tens of thousands of patients have died only because of this reason, according to reports.

It is widely believed by the experts in this area, if full public disclosure of the entire data of drug clinical trials was made, most of these new drugs would not have seen the light of the day and without putting many patients’ health safety in jeopardy.

All this is a part of a curious conundrum in the new drug approval process, across the world, for various reasons. In this article, I would try to dwell on this issue.

Voices against this ‘unethical practice’ getting louder:                                             

On December 22, 2015, ‘CBC News’ published an interesting article, titled “Researcher issues ‘call to action’ to force release of hidden drug safety data: Bringing drug industry data into the light of public scrutiny.”

The article echoed the same belief of other global experts and, in fact, went a step forward. It categorically reiterated, if full disclosure of the entire data of drug clinical trials is made public, medical practice might have been quite different.

To drive home this point, the article cited the example of the arthritis drug rofecoxib (Vioxx), which has been linked to tens of thousands of deaths related to heart attacks.

It highlighted, although this risk was very much known to the regulatory authority of the United States, the relevant data was not released to the public for an impartial scrutiny.

Quoting different sources, the paper observed, almost half of the drug trials remain secret and the studies that are published, overwhelmingly report results that make the drug in question look good.

Independent experts’ views differed from the innovator companies:

In some cases, when researchers were able to see what is hiding in the filing cabinets of the drug innovator companies, a different picture altogether emerged on the overall profile of those drugs.

One group looked at 12 antidepressants, comparing the published studies with the internal US FDA assessments. They found that 94 per cent of the published studies were positive, as compared to 51 per cent, when they included all of the studies assessed by the drug regulator.

Based on a detailed study, the authors concluded, without considering all the data, drug effectiveness can often be exaggerated, leading doctors and patients to assume that the medications work better than what they actually do. The ongoing practice of the drug players may help them to significantly diminish the risks, related to the benefits offered by these medicines.

A few months ago, another group analyzed the data from an unpublished drug company study about the effect of Paxil on teen depression and found that the drug did not work and was not safe for the patients. This result completely contradicted the original, unpublished study on this drug.

A crusader emerged in Canada:

Interestingly, the same article, as above, states that Mathew Herder , the health law associate professor at Dalhousie University in Halifax, Canada is now taking up the fight. He is now “calling on other doctors, researchers and journalists to bombard Ottawa with their own demands for drug industry data, using the new legislative lever called the ‘Protecting Canadians from Unsafe Drugs Act,’, which was passed late last year in Canada. 

He has also created a template to help doctors, researchers and journalists access drug safety data at Health Canada. Herder reportedly could even include biomedical researchers, doctors who prescribe medicine, investigative journalists pursuing questions about drug safety, and other activists and patient groups.

This example is worth imbibing elsewhere.

The ‘Rule Books’ are in place, though with loopholes:

To curb such alleged patient unfriendly practices of the innovative drug manufacturers, while obtaining the marketing approval of new drugs, various rules and procedure were put in place, by various authorities.

I shall deliberate below a few of these rules, and enough loopholes therein, enabling the interested parties to hoodwink the external experts, at the cost of patients.

International Clinical Trials Registry Platform:

Much before Herder, following a ministerial summit on Health Research in 2004, a World Health Assembly Resolution passed in 2005 called for unambiguous identification of all interventional clinical trials. This resolution led to the establishment of the ‘World Health Organization (WHO) International Clinical Trials Registry Platform’. It collates information on trials that have been notified in a network of clinical trial registries.

According to W.H.O, “The registration of all interventional trials is a scientific, ethical and moral responsibility”.

In the latest version of the Declaration of Helsinki, it reiterates, “Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject.”

It unambiguously states, “Researchers have a duty to make publicly available the results of their research …. Negative and inconclusive as well as positive results must be published or otherwise made publicly available”.

Understandably, W.H.O statement underscores, “There is an ethical imperative to report the results of all clinical trials, including those of unreported trials conducted in the past.”

It is worth mentioning here that on January 1, 2015, by a new policy on publication of clinical data, ‘European Medicines Agency (EMA)’ also decided to proactively publish all clinical reports submitted as part of marketing-authorization applications for human medicines, by the by pharmaceutical companies.

Big Pharma's serious apprehensions on greater Public transparency:  

Before finalization of the above policy, EMA sought comments on its draft from various state holders. On September 5, 2013, in its remarks on the draft, ‘The European Federation of Pharmaceutical Industries and Associations, EFPIA’ expressed its apprehension about the public health safety oriented proactive move by the EMA as follows:

“We are worried by a move towards greater transparency of clinical trials data that appears to be putting transparency – at whatever cost – ahead of public health interests. Our detailed response to the EMA draft policy speaks to this concern. While EFPIA values other voices and opinion in the conversation surrounding clinical trials data, we believe there are better alternatives than what the EMA is presenting.” 

This is of course understandable. That said, it also gives satisfaction to note that EMA did not wilt under any pressure on this score, whatever the anecdotal might of the external force be. 

Gross non-compliance, endangering patients’ health safety:

Although, the standards and requirements of “Public Disclosure of Clinical Trial Results” have been well specified now, and even in most of the Big Pharma websites one can find disclosure norms of clinical trial data, their overall compliance on the ground, is still grossly inadequate, endangering patients’ health safety.

An article published in the BMJ Open on November 12, 2015 titled, “Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012”, well captured the magnitude of this issue. 

Nevertheless, the study analyzed just a subset of drugs approved in a single year, 2012. The researchers only examined whether clinical trials were registered and reported, not what that data suggested about how the drugs worked.

The paper reported the results as follows:

“In 2012, the US FDA approved 39 novel new medicines, known as NMEs, and 35 novel drugs. Combining these lists, the FDA approved a total of 48 new drug entities, 15 of which were sponsored by 10 large pharmaceutical or biotechnology companies with market capitalizations valued over US$19 billion. A total of 342 trials were conducted to gain regulatory approval of the 15 drugs, 24 of which were excluded from our analysis, leaving 318 trials involving 99 599 participants relevant to our study, a median of 17 trials per drug.”

Based on the findings, the authors concluded asunder:

“Trial disclosures for new drugs remain below legal and ethical standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethical standards and the quality of medical knowledge.”

Simultaneously, The Washington Post in an article of November 12, 2015, titled, “How pharma keeps a trove of drug trials out of public view”, summarized this report by highlighting to the general public that one third of the clinical trial results that US FDA reviewed to approve drugs made by large pharmaceutical companies in 2012, were never publicly reported. 

Unethical practices skewing medical science:

On July 25, 2015, ‘The Economist’ published an article titled, “Spilling the beans’. It highlighted again that the failure to publish the results of all clinical trials is skewing medical science. 

This article also brought to the public attention that half of the clinical trial results are never published over several decades. It broadened the discourse with the observation that this specific unwanted practice, distorts perceptions of the efficacy of not just drugs, but devices and even surgical procedures too, in a well planned and a systematic manner. What is most important to note is, it has seriously compromised with patients’ health interest, across the world. 

It keeps on happening, as there are no firm obligations on the part of drug companies for making public disclosure of all such data, both for and against, though all these data are required to be filed with the regulatory authorities. Hence, the overall assessment of the drugs, weighing all pros and cons, is just not possible for any outside expert agency.

For granting necessary marketing approval, the designated authorities, at least theoretically, ensure that the drugs are reasonably safe, and have, at least, ‘some beneficial effects’. However, the prescribing doctors would continue to remain ignorant of the untold facts, the article states. 

According to ‘The Economist’, although in the United States the relevant laws were modified, way back in 2007, to address this issue, it still remains as a theory, the actual practices in this regard are mostly not so.

Despite vindication no tangible outcome yet:

As I said earlier, this fact got vindicated through extensive research by the ‘BMJ Online’ article and many other contemporary medical publications. 

For example, the evidence released earlier on  April 10,  2014 by the Cochrane Collaboration of London, UK, also shows that a large part of negative data generated from the clinical trials of various drugs were not disclosed to the public. 

Again, like Vioxx, though the US FDA was aware of all such data, for a well known drug Tamiflu, unfortunately the prescribing doctors were not. As a result, the U.S. Centers for Disease Control and Prevention (CDC), which doesn’t have the same access to unpublished data as the regulators, recommended this medicine not being able to evaluate it holistically. 

However, as the findings from the unpublished clinical trials eventually surfaced, CDC expressed serious apprehension on the overall efficacy of Tamiflu, quite contrary to the assessment of the concerned big pharma player.

Hence, despite quite a large number of vindications by the experts, no tangible outcome has been noticed on this pressing issue, just yet.                                                                

Conclusion:

Based on all this discussion, the moot question that springs up: Why do the doctors still prescribe such drugs, even after being aware of the full facts?

In this regard, an article titled, “Big Pharma Plays Hide-The-Ball with Data”, published in the Newsweek on November 13, 2014 raised a very valid question. 

It commented, even if Tamiflu does nothing, and there is just a slight chance of life-threatening side effects, why was it approved by the US FDA, in the first place?

Even more intriguing is: Why do the doctors continue prescribing these, especially after the Cochrane Collaboration took the Tamiflu’s maker, Roche, to task about many of its claims, in April 2014.

Incidentally, the Cochrane Collaboration is widely regarded as one of the most rigorous reviewers of health science data. It takes results of multiple trials, looks for faults and draws conclusions. It doesn’t accept funding from businesses with a stake in its findings.

The answer to this question may perhaps be too obvious to merit any elaborate discussion here. 

Be that as it may, this curious conundrum of ‘New Drug Approval’ with ‘Partial Public Disclosure of Clinical Trial Data’ needs to effectively addressed, without further delay. If not, patients’ health interest would continue to get seriously compromised with the continuation of prevailing laxity in its implementation process by the drug regulators.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Health Care: “India Has Moved From Strength To Strength!”

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The above flabbergasting assertion came recently from the Union Government of India in context of current health care system in the country. 

To be specific, this proclamation of the Ministry of Health was reportedly made at its ‘point by point rebuttal’ letter to the world’s leading medical journal of high repute - ‘The Lancet’, at the end of October 2015, in response to a news report on India’s frugal public expenditure on health. 

The chronicle:

On October 21, 2015 The Times Of India reported that shortly, a detail study in “The Lancet” would take Prime Minister Narendra Modi to task for failing in make public health a national priority area. It is happening despite his categorical promise of rolling out ‘Universal Health Coverage (UHC), during the last general election of India, in 2014.

The paper would be penned by some of the world’s foremost health experts and the issue is expected to be published on December 11, 2015.

In an interview with ‘The Times of India’, Richard Horton - the Editor-in- Chief of ‘The Lancet’, said that “health is an issue of national security for India, but Modi isn’t taking it seriously.”

Horton further commented, “I don’t see any new policies, any new ideas, any significant public commitment, and most importantly no financial commitment to the health sector, since he came into power in May, 2014.”

According to Norton, since Modi has come to power, health has completely lost focus of the Government. India is on the edge in this regard. If Prime Minister Modi does not tackle health, India’s economy combined with rising population is not sustainable. “The country’s healthcare system will collapse, if the government fails to invest in combating non-communicable diseases, such as, diabetes and heart problems”, he cautioned.

‘The Lancet’ to present contemporary fact-based analysis:                         

It is expected that the above article on India’s prevailing public health system, would be factual and analyzed based on the latest expert survey in this regard.

As I mentioned in my article of October 5, 2015 in this Blog titled, “Just 16% Of Indian Population Has Access To Free Or Partially-Free Health Care?”, the current Government has slashed union budgets for several ongoing and critical flag-ship schemes for health, such as:

  • Integrated Child Development Services
  • Mid-day meal
  • Aids and STD control
  • National Food Security Mission
  • National Rural Drinking Water Program

After a drastic reduction in union budgetary allocations for these crucial and very basic health schemes, there would possibly be no scope for any surprise in any quarter, if ‘The Lancet’ survey depicts a rather dismal overall public health care scenario in India.

Indian Government trashes ‘The Editor-in-Chief’s comment:

Trashing ‘The Lancet’ Editor-in-Chief’s above comments, Rakesh Kumar, Joint Secretary, Ministry of Health in a hard-hitting letter to Horton reportedly said:

“…launching an alphabet soup of program every quarter and not being able to implement them in true letter and spirit is a disservice to the people we serve.” 

According to this news report, the health ministry maintained that “no existing program” of the ministry has been “curtailed, stopped or truncated due to lack of funds”. It also highlighted that funding to states had been rationalized to break from the straight jacket of ‘one size fits all’ geographies and populations.

“India has moved from strength to strength and some of recent initiatives will ensure improved outcomes for the most vulnerable,” the letter re-iterated unequivocally.

“India has moved from strength to strength” – Government retorted: 

The above statement of the Union Ministry of Health that “India has moved from strength to strength” in health care, generally sounds bizarre and also absurd, to say the least. On the contrary, the available facts do not support this sweeping comment, as it were.

When compared with some much smaller neighboring nations of India and even Vietnam, it comes out clearly that they are doing far better on various critical health indicators.

This is vindicated by the ‘World Bank health indicators data’, which show that even Bangladesh, Nepal and Vietnam, with much lesser per capita GDP, are ahead of India in several key health indicators, as shown in the following table: 

Some Key Indicators India Bangladesh Nepal Vietnam
GDP Per capita(PPP) (Constant at 2011 US$) 2014 5445 2981 2261 5370
Life Expectancy At Birth (Female) 2013 68 71 70 80
Survival to Age 65 (% of Cohort) 2013 63 72 69 72
Public Health Expenditure (% of GDP) 2013 1.3 1.3 2.6 2.5
Infant Female Mortality Rate (Per 1000 Live Births) 2015 38 28 27 15
Mortality Rate (Under 5 year of Live Births) 2015 48 38 36 22
Maternal Mortality Ratio (per 1000 Live Births) 2013 190 170 190 49
Rural Population With Improved Access to Sanitation Facilities (%) 2015 29 62 44 70
Vitamin A Supplementation Coverage Rate (% of Children 6-59 months) 2013 53 97 99 98
Immunization DPT (% of Children 12-23 month) 2014 83 95 92 95

(Source: Live Mint, October 28, 2015)

Similarly, another 2011 study published in the ‘The Lancet’ reported that ‘Out of Pocket’ expenditure on health in India is the highest, again even as compared to its much smaller neighbors, as follows:

Country Out of Pocket Expenditure on Health (%)
Maldives 14
Bhutan 29
Sri Lanka 53
India 78

As I said before, these are just a few examples. In this article, I shall not dwell further on such comparisons, which are already known to many. 

Instead, I would prefer to underscore, as many scholarly research papers have already done, that GDP growth of a nation cannot be driven in a sustainable manner without putting in place a robust public health care system in a country. 

Reasonable public investment is necessary to improve health indicators:

If India wants to improve its key health indicators and surpass the achievements of just not smaller countries, such as, Nepal, Bangladesh, Sri Lanka, Maldives, but all other BRICS (Brazil, Russia, China and South Africa) nations, India needs to hike up its public health budget significantly, together with speedy implementation of all identified health projects.

According to the World Bank 2004 report (p56), for developing or middle-income countries with institutions of an acceptable quality, a 10 percent increase in public health expenditures as a proportion of the GDP, would be associated with a 7 percent decrease in the maternal mortality rate, a 0.69 percent decrease in child mortality rate, and a 4.14 percent decrease in low weight for children under five years of age.

Impact of health on economic growth shouldn’t be underestimated:

Between ‘public health’ and ‘other economic growth drivers’, choosing just one as priority focus area, could well be futile, in the long run. This is by no means an ‘either/or’ situation, at all. The Government should take into cognizance that there is a heavy price tag attached on an underestimation of the impact of health on economic growth, which could put its core objective of a sustainable high GDP growth in jeopardy.

I would now illustrate this point with no more than three examples, out of so many available.                                                                                   

According to the ‘World Health Organization (WHO)’, “Good health is linked to economic growth through higher labor productivity, demographic changes and higher educational attainment. In the same way, poor health undermines economic growth.”  

India, though, seems to be chasing a high economic growth with all guns blazing, apparently does not believe in this fundamental dictum; neither does the Government accept that current public health care system is generally pathetic in the country and virtually on the verge of crumbling, if inaction continues.

To underscore the same point that impact of health on the economy should not be underestimated, I now quote from another study hereunder.

A December 2012 paper published in the “Global Management Journal” titled, “The Connection Between Health and Economic Growth: Policy Implications Re-Examined”, concluded as follows: 

“Evidence presented in this paper illuminates the two-way relationship between economic growth and health. Bearing in mind the substantial influence of enhanced health to economic productivity and growth, governments need to look at health expenses as an investment rather than a cost”.

My third example would be another paper published in ‘OECD Observer’ titled, “Health and the economy: A vital relationship”, written by Julio Frenk, Mexican Minister of Health and Chair of the 2004 meeting of OECD Health Ministers. This paper too reiterates that the impact of health on the economy should not be underestimated. Thus, our challenge today is to harmonize health and economic policies to improve health outcomes.

Julio Frenk further emphasized, “The effects of health on development are clear. Countries with weak health and education conditions find it harder to achieve sustained growth. Indeed, economic evidence confirms that a 10% improvement in life expectancy at birth is associated with a rise in economic growth of some 0.3-0.4 percentage points a year.”

Here comes the critical importance of improving ‘Human Development Index (HDI)’ ranking of India to achieve a high and sustainable GDP growth, as the nation moves on.

 Improve ‘Ease of doing business’ and ‘Human development’ indices together: 

According to ‘World Bank’s Doing Business Report 2016’, India has moved up four rungs in the global rankings for ‘ease of doing business’. The country now ranks 130 among 189 countries, against its last year’s ranking of 134. This is a significant achievement, which has been widely publicized by the Government and very rightly so. 

Whereas, according to the latest (2014) ‘Human Development Index (HDI) report, published annually by the ‘United Nations Development Program (UNDP)’, India ranks 135 out of 187 countries across the world. The next HDI report is expected to be launched in November 2015.

HDI is a statistical tool used to measure a country’s overall achievement in its social and economic dimensions. It captures a composite statistic of life expectancy, education, and per capita income indicators, which are used to rank countries into four tiers of human development.

Increase in life expectancy is a composite outcome of long-term effectiveness of a robust public health care system in the country.

Interestingly, the present Government does not talk much about HDI. Its primary focus seems to be now on ‘ease of doing business’, though for a sustainable high economic growth of a nation both should be speeded up and right in tandem. 

Conclusion: 

Reducing Union Budget allocation on health substantially and passing the responsibility of the same to the States with no assigned accountability for implementation on the ground, may not work in India. 

Even if the comments of Richard Horton, the Editor-in-Chief of ‘The Lancet’ on this score, are brushed aside with contempt, his factual observations should be noted as valid suggestions. Accordingly, much required action steps need to be factored in by the Government in its 20116-17 Union Budget planning process.

Before concluding, I would very humbly, respectfully and with all humility submit that the Union Government should always be open to outside experts’ comments and suggestions, especially on public health in the country, to initiate a constructive debate. Any voice of discord or dissent, either on Governments’s action or inaction or both, may not necessarily be construed as an act against the national interest.

In this context, I am curious to know, what happened when on October 19, 2015, the Union Cabinet Minister for Women and Child Welfare – Mrs. Maneka Gandhi, who oversees a scheme to feed more than 100 million poor people, reportedly expressed her anguish and concerns in public. She openly said that slashing of her Ministry’s budget by half to US$1.6 billion, has hit her plans to strengthen the fight against ‘Child Malnutrition’ and makes it difficult to pay wages of 2.7 million of health workers.

Leave aside ‘The Lancet’ squabble for a moment. Does the above public anguish of a senior Union Cabinet Minister, in any way, depict that “India has moved from strength to strength” in health care?

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Does India Produce ‘World Class’ Medicines, For All?

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India has already achieved a staggering number In terms of quantity or volume of generic medicines that it produces not just for India, but for many developed, developing and poorer countries, across the world. For this reason, India is popularly known as ‘The Pharmacy of The World’. No one questions this number at all, rather looks at India with a sense of admiration in this regard.

Nevertheless, for driving this volume growth trend further north, in a consistent and sustainable way, Indian pharma sector must ensure that its huge volume growth engine remains firmly placed on a solid bedrock of ‘world class’ drug quality, always. Any compromise in this crucial area, could strike a critical blow to this ‘tower of national pride’.

Ongoing several embarrassing incidents related to the drug manufacturing quality standards in India, are increasingly fueling the apprehension, whether or not India produces ‘World Class’ medicines for all patients across the world, independent of any other criteria, financial or otherwise. The debate has now taken an interesting turn, especially after near confirmation of this apprehension by the top drug regulator of India.

In this article, I shall discuss this important issue that hugely impacts all of us, giving my own perspective to it. Let me begin with one of the most recent incidents on the subject, involving the numero-uno of Indian pharmaceutical industry.

An overseas new product launch got prematurely aborted?

On September 25, 2015, by a Press Release, Sun Pharma Advanced Research Company Ltd. (SPARC) announced a major set back for the company. The set back may not be so much in terms of the company’s estimated revenue loss, but more on public perception across the world, about the manufacturing quality standards followed even by the top most pharma company of India.

SPARC made a public announcement through media that on March 2015 it had received a final approval from the Food and Drug Administration of the United States (USFDA) for the anti-epileptic drug – Elepsia XR (Levetiracetam extended-release tablets 1000 mg and 1500 mg). However, in the Complete Response letter (CRL) to the company’s New Drug Application (NDA) for the product, the USFDA has revoked its earlier approval, citing that the compliance status of the manufacturing facility was not acceptable on the date of approval. Elepsia XR is to be manufactured at Sun Pharmaceutical Industries Ltd (SPIL)’s Halol facility in Gujarat, the announcement said.

Sun Pharma had reportedly indicated in June 2015 that the Company had been working “very aggressively” to find partners for the product. It had “some advanced discussions” and aimed to launch the drug by the second half of fiscal 2016.

The international media lapped it up and reported this development with eye-catching headlines, one such was:

“India’s Sun Pharma research arm sees FDA nod for Elepsia XR yanked by FDA on manufacturing.”

Not a one-off isolated incident:

This matter can no way be treated as a one-off and an isolated incident, as it fits in well with a series of similar events, spanning over the last few years.

Looking at these disturbing adverse reports from the foreign drug regulators on the drug manufacturing quality standards in India, together with recent comments of the Indian drug regulator on the subject, serious health safety concerns on overall drug quality in the country, are being expressed now. The concern includes the local patients in India, as well.

Can the core issue be wished away?

Up until today, USFDA has altogether warned 39 manufacturing sites of 27 Indian pharma companies for breach of data integrity and not following specified manufacturing quality standards. The agency has also expressed that it treats these as potentially dangerous medicines for the consumption of patients in the US.

In 2015 alone, USFDA has reportedly detected such serious ‘short comings’ with 6 Indian drug makers, till September. A report from Financial Times (FT) states that the above numbers do not include the testing facilities facing sanctions from the European Medicines Agency (EMA) in the GVK Biosciences related cases or from the World Health Organizations (WHO).

What is most worrying, none can possibly still fathom, if these alleged ‘reprehensible’ manufacturing practices are restricted to just a few players or are all pervasive across the Indian drug industry.

When the foreign regulators, such as USFDA and Medicines and Healthcare Products Regulatory Agency (MHRA) of the United Kingdom (UK) continue raising the red flags on the manufacturing standards of the top pharma players of India, including the numero uno, a chilling sensation flows through the spine, as it were. The moot question that comes up: Are all the drugs manufactured in India safe for the local patients, offering desirable efficacy?

Keeping these in perspective, would it be prudent to wish away the drug quality related critical issues, raising a conspiracy theory against the US or EU or suspend discussions on any Foreign Trade Agreement (FTA)? I don’t reckon so, and would touch upon this point in course of my discussion below.

The murmur among the US doctors:

According to an article from Reuters of March 18, 2014, titled “Unease grows among US doctors over Indian drug quality”, some US doctors are also expressing concerns about the quality of generic drugs supplied by Indian manufacturers, following a flurry of recalls and ‘import bans’ by the USFDA.

This concern has been prompted by the fact that India supplies about 40 percent of generic and over-the-counter drugs used in the United States, making it the second-biggest supplier after Canada.

Not much complaint from the Indian doctors:

This is intriguing. Despite so much of furore of the regulatory agencies in the US and EU on the Indian drug quality standards, not much concern on the same has been expressed by the medical practitioners in India, just yet.

It appears, by and large, Indian doctors believe that branded generics are generally of good quality, and the quality of generics without a brand name is not as reliable, always.

This logic is beyond my comprehension. How come just fixing a brand name on a generic formulation makes it more acceptable in terms of quality, when both branded generics and generics without a brand name, have obtained the same regulatory approval from the same drug regulators in India and following the same regulatory process?

As you will see below, the situation has changed further now, especially after the admission of the DCGI about non-compliance of global manufacturing quality standards by majority of the formulation manufacturers in India, as reported by the media. The only silver lining to it is that whatever is being currently manufactured in India, presumably meets the regulators approval in conformance to the Drugs and Cosmetics Act of the country, without any credible data to the contrary.

Does India produce drugs of ‘World Class’ quality for all?

The key question that is being raised today: Does India produce ‘world class’ drugs and for all? This is mainly because, manufacturers of ‘world class’ drug quality always aim at competing for quality on the best global standards to remain competitive in the international markets, in all parameters. This should hold good even for the domestic Indian market, for all drugs, consumed by all the local patients, irrespective of their financial status.

A lurking fear keeps lingering, primarily apprehending that Indian drug manufacturing quality related issues are not confined only to the importers in the developed world, such as, the United States, European Union or Canada. There is no reason to vouch for either, that such gross violations are not taking place with the medicines consumed by the patients in India or in the poorer nations of Africa and other similar markets.

A recent international study on Indian drug quality:

The following study further aggravates the angst.

The September 2014 ‘Working Paper 20469’ of ‘The National Bureau of Economic Research (NBER)’ Cambridge, USA, titled “Poor Quality Drugs and Global Trade: A Pilot Study’, epitomizes the following:

  • Experts claim that some Indian drug manufacturers cut corners and make substandard drugs for markets with non-existent, under-developed or emerging regulatory oversight, notably Africa.

The study assessed the quality of 1470 antibiotic and tuberculosis drug samples that claim to be made in India and were sold in Africa, India, and five mid-income non-African countries and found:

      – 10.9 percent of these products fail a basic assessment of active pharmaceutical                  ingredients (API) 

       - The majority of the failures are substandard (7 percent) as they contain some correct          API but the amount of API is under-dosed.

        – The distribution of these substandard products is not random, they are more likely             to be found as unregistered products in Africa than in India or non-African                           countries.

Claiming that the findings are robust, the NBER study points towards one likely explanation that Indian pharmaceutical firms and/or their export intermediaries do indeed differentiate drug quality according to the destination of consumption.

Incomprehensible?

The above facts are alarming, especially when these flow from a survey report of a credible international institution. This is incomprehensible too, as all these are medicines, and are meant to be for relief or cure of ailments that the patients are suffering from, irrespective of whether they are from the developed, developing or poorer countries.

If it is still happening today, why are those manufacturers allowed by the Indian drug regulators to discriminate between the patients of the developed countries and the developing world, including India, to meet the same health care needs? This is absolutely cruel by any standard, undoubtedly.

‘As you sow, so shall you reap’:

Just as the above well-known proverb says that the actions or deeds repay in kind, reasonably frequent ‘import bans’ by the foreign drug regulators on drug quality norms, has probably prompted booming generic drug exports of Indian pharma now slowing down to US$15.3 billion in 2014-15, from US $14.84 billion in 2013-14.

Along side, these avoidable incidents have significantly dented India’s image as the ‘pharmacy of the world’, manufacturing affordable and high quality generic formulations for the patients across the world.

Indian drug regulator too now thinking afresh? 

Yet another relevant question comes up. What happens, if during treatment of serious ailments such drugs fail to act for inferior quality? How would one possibly know in India, whether a death has occurred due to unresponsive poor quality of drugs or on account of severity of the ailments? How helpless are the patients in such a situation?

This sad feeling gets even stronger, when well after a prolonged defense of the high quality of drugs manufactured in India, no less than the Drug Controller General of India (DCGI), airs his second thought on the same issue. This is vindicated by recent media reports on this subject.

On September 30, 2015, a media report stated that being virtually flustered by the USFDA and the drug regulators in the European Union, the Drug Controller General of India (DCGI) would place a proposal before the Ministry of Health, within the next six months, for an amendment to the existing pharmaceutical manufacturing laws under Drugs and Cosmetics Act, 1940, and Drugs and Cosmetics Rules, 1945, in order to ‘bring them on par with international standards’.

The DCGI now believes that this remedial measure would raise drug manufacturing standards in India in line with the global cGMP standards, recommended by the World Health Organization (WHO).

Currently, out of around 8,000 drug manufacturers in India, only 10 to15 percent are following the WHO guidelines, the report stated quoting the DCGI.

The new revelation further strengthens the apprehension about quality of drugs that Indian patients are consuming in the country with a strong hope for relief from the diseases that they suffer from.

The DCGI apparently admitted it, when he was quoted saying in the above report, “India has become a pharmacy of the world. So, we cannot live in isolation and will have to meet their expectations. Our system is in the process of improving.”

DCGI statement follows an important Government decision:

It is worth noting that the above comment of the DCGI comes close on the heels of an important Government decision in this regard.

On August 12, 2015, The Press Trust of India (PTI) reported that to facilitate domestic manufacture of quality medical products, the Cabinet Committee on Economic Affairs (CCEA) on that day approved a proposal of strengthening and upgrading the drug regulatory system both at the Central and state level. The committee approved a budget of of INR17.5 billion (US$270 million) on this account.

The up gradation and strengthening of the system will also include setting up of new laboratories and training academy for regulatory and drug testing officials, the report added.

Yet Another significant development:

On October 5, 2015, in yet another significant development in this direction, the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom (UK), by a ‘Press Release’, announced signing of a Memorandum of Understanding (MOU) with the Central Drugs Standard Control Organization (CDSCO) of India.

This agreement will increase collaboration between India and UK in the area of medicines and medical devices with the aim of further improving public safety in both the countries. It is worth noting, around 25 percent of generic drugs consumed in the UK are made in India. Hence, the concern of MHRA over the safety of those medicines is understandable.

I wrote in this Blog on USFDA ‘Import Bans’ in my article of November 11, 2013, titled ‘USFDA ‘Import Bans’: The Malady Calls For Strong Bitter Pills.’

Conclusion:

A valid question that is being asked by many in India today, why the issues like, alleged cGMP non-compliance, data fudging and falsification of other documents, especially with USFDA, have multiplied suddenly over the last few years. Why not as many of such issues were raised by the USFDA before around 3 to 4 years?

This is primarily because, of late the inspectors from the USFDA have significantly increased their efforts to ensure the drug manufacturing facilities from where both generic Active Pharmaceutical Ingredients (API) and formulations are exported to the US, strictly follow the drug manufacturing standards, as stipulated by the USFDA. The fact that India supplies about 40 percent of generic and over-the-counter drugs currently used in the United States, has prompted this requirement to safeguard health safety of the American patients.

Such stringent USFDA audits commenced in 2012, when US Congress passed the FDA Safety and Innovation Act. This legislation, among others, requires the USFDA auditing all foreign facilities that make drugs for export to the US, as frequently as it does for the domestic drug manufacturing plants. Thereafter, we have seen a spurt in the USFDA inspections of the pharma manufacturing facilities in India, where from drugs are exported to the US. Hence, there does not seem to be any other credible ‘conspiracy theory’ on this issue.

As reported in ‘The New York Times’ of February 14, 2014, the same DCGI almost brushing aside the gravity of the situation arising out of repeated ‘import bans’, commented at that time, “If I have to follow US standards in inspecting facilities supplying to the Indian market, we will have to shut almost all of those.”

The top drug regulator seems to have changed his mind since then, and presumably is thinking differently now, as the Indian media very recently quoted the DCGI saying “India has become a pharmacy of the world. So, we cannot live in isolation and will have to meet their expectations. Our system is in the process of improving.”

This is a good omen, especially for the patients in India. If and when it gets translated into reality, with Kudos to the DCGI, we all would feel very proud saying, “The Pharmacy of the World now produces the World-Class drugs, for all” …God willing!

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Just 16% Of Indian Population Has Access To Free Or Partially-Free Health Care?

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Is health care currently a low priority area for the Government of India? Probably yes, and thus it is worth trying to fathom it out.

Besides planned frugal spending on overall public health in 2015-16, even as compared to the past trend, two other health related budgetary decisions of the Government are indeed baffling, at the very least.

As many of you, I too know that the incumbent Government in its first full-year budget of 2015-16 has sharply reduced the budgetary allocation on many important health related other projects, such as:

- Union budget allocation for the National Rural Drinking Water Program (NRDWP) that aims at providing safe drinking water to 20,000 villages and hamlets across India, has been drastically reduced this year. Curiously, this decision has been taken at a time, when India loses 200 million person days and Rs 36,600 crore every year due to water-related diseases.

- The Integrated Child Development Services (ICDS) scheme, which provides food, preschool education, and primary health care to children under 6 years of age and their mothers, has also been hit by a 54.19 percent budget cut this year. This decision too of cutting public expenditure on food, nutrition and health care for children to more than half, defies any logic, especially when 40 percent of growth stunted children in the world are reportedly from India, exceeding the number of even sub-Saharan Africa.

I hasten to add that the Union budget 2015-16 has indicated, as the states’ share in the net proceeds of the union tax revenues has increased, as per recommendations of the 14th Finance Commission, these central Government programs will now be run with a changed funding pattern between the Union and states. However, according to financial experts in these areas, regardless of devolution, the total money available to run these critical projects is sharply decreasing.

That said, on the other pages of the same Union Budget, public funding in the current fiscal year for bridges and roads has more than doubled. The budgetary allocation for these two areas now stands more than even education.

I deliberated on similar subject of access to health care in my blog of March 16, 2015, titled, “With Frugal Public Resource Allocation Quo Vadis Healthcare in India?”

Health care sector is important for job creation too:

According to the World Health Organization (WHO), health care sector is one of the largest job creators, not just in India, but globally. Thus, Indian health care industry being one of the fastest growing industrial turf in the country with a reasonable base, deserves a sharper focus of the Government.

Additionally, the socio-economic benefits that this sector provides in creating a sustainable, healthy and highly productive work force, has been well documented and can’t just be wished away, in any case.

The neglect is intriguing:

Currently, total healthcare spend of India is no more than 4.2 percent of the GDP with public spending being just 1.2 percent of it. Other BRICS nations are way ahead of India, in this area too. To set a direction on country’s public healthcare spend, breaking the jinx of a long period of time, the draft National Health Policy 2015 of the Government aimed at initial increase in health expenditure to 2 percent of the GDP.

As a result of the legacy of neglect over a long period of time, which continues albeit more blatantly even today, only 16 percent of the Indian population declares today that they have access to free or partially-free health care. I shall dwell on this area subsequently in this article.

Keeping these in perspective, it was intriguing, when the union budgetary allocation for health care in 2015-16 was kept at Rs. 297 billion or U$4.81 billion for its main health department, almost the same outlay as in the previous budget.

When compared against public fund allocations, such as, US$ 93 billion for highway projects or US$ 7.53 billion for 100 smart cities in the country, one will get a realistic perspective of this meager health budget allocation, in terms of effectively addressing the health care needs of around 1.25 billion people of India. Over 70 percent of this population live in the hinterland.

Agreed that the Government focus on these ‘infrastructure projects’ are not unimportant by any means. Nevertheless, the above comparison only highlights how much priority the Government assigns to the health care sector of India and for the health of its citizens. This issue assumes even greater significance in combating several challenging health situations, such as, ongoing fight against increasing incidence of life-long chronic ailments and deadly life-threatening diseases like, cancer, fueling already high rate of morbidity and mortality in the high country.

A quick glimpse on a few outcomes of neglect:

The Working Paper No. 1184 dated January 8, 2015, titled “Improving Health Outcomes And Health Care In India” of the Organization for Economic Co-operation and Development (OECD), highlights some interesting points, as follows:

  • Chronic diseases are the biggest causes of death and disability accounting for 50 percent of deaths, with cardiovascular diseases and diabetes, respiratory conditions and cancers figuring most prominently.
  • Preventive interventions such as improving access to a clean water supply, reducing the spread of HIV/AIDS through better sexual education, and vaccination campaigns for other diseases will each deliver more significant returns in life years.
  • Vaccination rates for diphtheria, tetanus and pertussis, for measles and for hepatitis B are all much lower than in OECD and peer countries.
  • Minimal access to free or partially-free health care.

It is an irony that ‘life expectancy’ in India still remains well below the countries at a similar level of development.

Abysmal overall hygienic conditions:

The OECD survey brings to the fore  abysmal hygienic conditions still prevailing in India. It can only be improved through active intervention of the Government with necessary budgetary allocations, sans photo ops for some celebrities and most politicians. Sincere support and participation of the civil society and intelligentsia, in general, are also equally important.

The paper underscores, among others, the following extremely unhygienic conditions still prevailing both in urban and rural India:

  • Most households in rural India do not defecate in a toilet or latrine, which leads to infant and child diseases (such as diarrhea) and can account for much of the variation in average child height. Even today the sight of poor children defecating openly in the streets, that too in a city like Mumbai, is also not very uncommon.
  • The burning of solid fuels in particular (undertaken by more than 80 percent of the population in cooking) is a major risk factor behind ischemic heart disease, lower-respiratory tract infections and chronic obstructive pulmonary diseases and could also increase cataracts and stroke.
  • Exposure to air pollution is a significant problem.
  • Many of the poor continue to smoke heavily.
  • 11 of the lowest income quintile did not undertake sufficient physical activity, compared with 16 percent in the highest income quintile.

India provides minimal access to free or partially-free health care:

As I mentioned above, India provides minimal access to free or partially-free healthcare to its citizens, as compared to all the BRICS nations, many other countries in South East Asia and even in Africa.

The above OECD paper states that with poor health intertwined with poverty, the greatest gains lie with policies that address the social conditions which enable combating communicable and non-communicable diseases.

Among BRICS countries, India provides least access to ‘Free or Partially-Free Health Care’ Services to its general population. This is despite being the largest democracy in the world, which is now striving hard to emerge as an economic and military superpowers.

The following study shows that only 16 percent of the Indian population declares having access to free or partially-free health care from the government:

BRICS Countries % surveyed said ‘Yes’ to the question: “Does your household have access to free or partially free health care from the State”
India 16
Brazil 24
China 73
Russia 96
South Africa 62

Source: Credit Suisse Research Institute, Emerging Consumer Survey Databook 2014.

As the OECD paper states, in this study approximately 1500 respondents were surveyed in each country, with India and China both having larger sample size of 2500. The male-to-female split between respondents was roughly 50:50 in all cases with rural-to-urban split varying by country.

Poor satisfaction level with existing health care services:

This is very important; as public facilities are the predominant source of qualified health professionals in rural areas where much of the Indian poor reside. In addition, significant population growth is occurring in urban slums, where urban public health care facilities are struggling to provide basic services. In a situation like this, slum dwellers face challenging economic barriers to accessing expensive private health care services (MoHFW, 2012).

The OECD survey indicates that 41 percent of those in rural areas and 45 percent in urban areas were not satisfied with treatment by their doctors or facility.

The reason attributed to this dissatisfaction are as follows:

  • Distance was cited by 21 percent of people in rural areas and 14 percent in urban areas.
  • Public health care centers remain closed more than half the time and lack basic medical supplies, such as stethoscopes and blood pressure scales.
  • Non-availability of required services was cited by 30 percent of people in rural areas and 26 percent in urban areas.

This is quite credible, as according to the Government’s own estimates:

- 10 percent of primary health care centers are without a doctor

- 37 percent are without a laboratory technician

- 25 percent without a pharmacist (MoHFW, 2012)

The above picture is quite consistent with large scale surveys in poor communities of India, by OECD.

Health care business for up market is booming:

Growing inequitable distribution of healthcare products and services is now wide open and blatant, more than ever before. There is no signal yet that the Government would soon consider health care sector as its one of the key focus areas, along with education, just as infrastructure, such as, building roads, highways, e-highways, flyovers, bridges and smart cities.

For up-market patients, the private sector is creating world class facilities in India. We can see today a good number of ‘five-star’ hospitals, with more number of newer ones coming up offering jaw-dropping facilities, quite akin to, may be even surpassing what are being offered for patients’ luxurious comfort in the developed world. Although these facilities cost a fortune, one would usually need to be in a queue to get admitted there for any medical or surgical treatment.

Most of these hospitals are now in high demand for ‘medical tourism’. According to available reports India currently caters to health care needs of over 200,000 foreign patients. ‘Medical tourism’ business reportedly fetched around US$ 2 billion to India in 2012.

On the flip side of it, as we all read in the recent media reports, some of these hospitals in Delhi refused admission even to seriously ill dengue patients, as they can’t afford such facilities. A few of these patients ultimately succumbed to the disease and the parents of one such poor child, who died without any hospital treatment in that process, committed suicide unable to withstand the irreparable and tragic loss.

Giving ‘Infrastructure Status’ to health care sector:

When creating basic infrastructure is the priority area of the present Government for financial resource allocation, why not give ‘infrastructure status’ to the health care sector now? This is not just for the heck of it, but purely based on merit and earlier detail evaluation by a Government Committee of experts.

To address the critical health care needs for the vast Indian population with appropriate infrastructure, quality products, services and manpower, providing ‘infrastructure status’ to the health care sector could facilitate the whole process. Additionally, it can transform the Indian healthcare sector as one of the biggest job-generating industry too.

This has been a key demand of the industry until recently, though not so much being talked about it today. A few years back, the previous Government was reportedly mulling to assign full fledged infrastructure status to the healthcare sector, as it merits inclusion in the category of ‘infrastructure’, satisfying all the nine criteria set by the erstwhile Rangarajan Committee.

I find in my archive, the Confederation of Indian Industry (CII) also demanded ‘infrastructure status’ for the health care sector in its pre-union budget memorandum for 2010-11. In that proposal CII had estimated that health care industry in India requires an investment of around US$80 billion, whereas in the current fiscal year the public expenditure on health still languishes at U$4.81 billion.

This specific issue seems to have taken a back seat today, for reasons not known to me. However, it is interesting to note that not just the Government apathy, no such demand is being made today by the large multi-industry trade associations of India, as vociferously as we witness, for example, in the case of ‘The Goods and Service Tax (GST) Bill’.

Health care debate is not to the fore today:

Critical health care issues of the country don’t seem to be in the fore front today for comprehensive debates even for the Indian main stream media, to influence the government.

We have been experiencing for quite while that Indian media, including social media, in general, usually goes ballistic 24×7 mostly with selective sensational topics. These may include, among others…glitzy events on Government’s high profile advocacy initiatives to attract more Foreign Direct Investment (FDI) from large overseas companies…Or back home some unfortunate and tragic Dengue fever related deaths due to negligence just in Delhi, though the same and equally grave incidences taking place in the other states of India, are hardly getting any coverage…Or on some high profile alleged murder pot-boilers announcing media verdict conclusively, even before completion of police investigation and charge-sheet being filed in a court of law.

These are probably neither bad, nor unimportant, nor avoidable, nor can come within the ambit of any media criticism. I am also not trying to do that, either.

As the saying goes, variety is the spice of life. We, therefore, generally want to get a feel of it everyday early in the morning, mostly glancing through the newspaper headlines, or in the late evening watching impatient anchor with strong personal opinion trying hard to dominate over all other participants in high-decibel ‘TV debates’, as these are called by the respective channels.

In an era of sensationalized and eye-ball grabbing ‘Breaking News’ of all kinds, flashing everywhere almost every now and then, critical health care issues seem to have become a mundane subject to the newsmakers for any meaningful debate to influence the Government. Serious debates on critical health care issues presumably would not generate all important Television Rating Points (TRPs) to the TV channel owners. Though I have no idea, the TRP of such debates  probably has been estimated to be even lesser as compared to the cacophony aired by the TV channels on the cost to exchequer for the MPs subsidized meals in the Indian Parliament…with intermittent high pitch ‘war cry’ of the dominating anchor… ‘the nation wants to know this’.

Conclusion:

Be that as it may, health care environment impacts all of us, quite appreciably. There is not even an iota of doubt on it. However, we can feel it mostly when the reality hits us or our families hard…very hard, as serious and cruel ailments strike suddenly, or as we face avoidable disease related deaths of our near and dear ones, or when illness makes a loving one virtually incapacitated, even after facing financial bankruptcy.

Health care is a serious matter for all of us, just as it is a serious and critical business for every nation and every Government. This criticality factor is independent of whatever level of economic development the country is aspiring for. Thus, the indifference of the Indian Government, if I may say so, despite promising so much on health care earlier this year, is intriguing, and more so, when just 16 percent of the total population has access to free or partially-free health care in our India of the 21st century.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

India To Expand NLEM 2011: A Step In The Right Direction

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Responding to growing discontentment on the flawed National List of Essential Medicines 2011 (NLEM 2011) and equally vociferous demand for its urgent rectification, on May 5, 2015, in a written reply to the Lower House of Indian Parliament (Lok Sabha) the Union Minister for Chemicals and Fertilizers – Mr. Ananth Kumar made the following submission:

“The Ministry of Health and Family Welfare, has constituted a Core Committee of Experts to review and recommend the revision of National List of Essential Medicines (NLEM) 2011 in the context of contemporary knowledge of use of therapeutic products.”

According to earlier media reports, the Government had formed this Core Committee in May 2014 under Dr. V.M Katoch, Secretary, Department of Health Research (DHR) and Director General, Indian Council of Medical Research (ICMR). However to utter dismay of many, even in a full year’s time, the Committee has not been able to come out with any tangible recommendations in this area.

In his reply from the floor of the Parliament, the Union Minister added with a tinge of reassurance:

“The Core committee has already held wide consultations with stakeholders and is likely to come out with its recommendations on the revised NLEM soon… The revised NLEM would form the basis of number of medicines which would come under price control,”

This reply from the Minister was in response to a query from a lawmaker on what steps have been taken by the Government to expand the list of NLEM 2011 and provide them to the poor at affordable prices.

Mr. Ananth Kumar also reiterated, the National Pharmaceutical Pricing Authority (NPPA) has already fixed the ceiling prices in respect of 521 medicines till date, out of 628 NLEM formulations included in the first schedule of DPCO, 2013.

“The revised NLEM would bring more drugs under price control”, the Minister said.

NPPA’s earlier initiative was thwarted:

It is worth noting that in 2014, to include all drugs of mass consumption, in addition to essential and life saving medicines, NPPA initiated an exercise to expand the NLEM 2011.

At that time, quite rightly I reckon, the pharmaceutical industry vehemently protested against this regulatory overreach of NPPA and sought judicial intervention at least in two High Courts of India.

Moreover, as is well known today, NPPA’s attempt to regulate prices of medicines of mass consumption got thwarted, when the Union Government intervened and directed the price regulator to withdraw its related internal guidelines. Coincidentally this lightning action was taken just before Prime Minister Narendra Modi’s schedule visit to the United States in end 2014.

Be that as it may, the industry observers consider the last week’s announcement of the Union Minister, from the floor of the Parliament, to expand the span of NLEM 2011 as a step in the right direction for improving access to affordable essential medicines for all in India.

A brief backdrop for ‘Essential Medicines’:

The World Health Organization (W.H.O) has defined ‘Essential Medicines’ as those that ‘satisfy the priority healthcare needs of the population’. It has been propagating this concept since 1977, when W.H.O published the first Model List of Essential Drugs with 208 medicines. All these medicines together provided safe, effective treatment for the majority of communicable and non-communicable diseases, at that time.

Every two year this list is updated. The current Model List of Essential Medicines, prepared by the W.H.O Expert Committee in April 2013, is its 18th Edition.

According to W.H.O, such ‘Essential Medicines’ are selected with due regard to disease prevalence, evidence on efficacy and safety, and comparative cost-effectiveness. The Organization categorically states:

“Essential medicines are intended to be available within the context of functioning health systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality, and at a price the individual and the community can afford.”

Many countries of the world, India included now, have the National List of Essential Medicines (NLEM) and some have provincial or state lists as well, such as, in Tamilnadu Rajasthan and Delhi.

Health being a state subject in India, NLEM usually relates closely to Standard Treatment Guidelines (STGs) for use within the State Government health facilities. Ironically, such measures are currently being taken by just a small number of State Governments in the country.

NLEM – A forward-looking ongoing concept:

According to W.H.O, the concept of ‘Essential Medicines’ is forward-looking and ongoing. This idea prompts the need to regularly update the selection of medicines in the NLEM, reflecting:

  • New therapeutic options
  • Changing therapeutic needs
  • The need to ensure drug quality
  • The need for continued development of better medicines
  • Medicines for emerging diseases
  • Medicines to meet changing resistance patterns

As a part of its ongoing exercise, on May 8, 2015, The World Health Organization (W.H.O) by a ‘News Release’ announced addition of several new treatments for cancer and hepatitis C to its list of ‘Essential Medicines’, which the agency believes should be made available at affordable prices.

All 5 new products for the treatment of Hepatitis C, including sofosbuvir and daclatasvir, were included in the List. These medicines cure more than 90 percent of those infected and cost from US$63,000 to US$94,500 in the United States, depending upon the drug and treatment regimen.

Considering, new breakthroughs made in cancer treatment in the last years, W.H.O also revised the full cancer segment of the Essential Medicines List this year: 52 products were reviewed and 30 treatments confirmed, with 16 new medicines added in the list, including Herceptin of Roche, and Gleevec of Novartis.

“When new effective medicines emerge to safely treat serious and widespread diseases, it is vital to ensure that everyone who needs them can obtain them,” said W.H.O Director-General, Dr Margaret Chan. “Placing them on the WHO Essential Medicines List is a first step in that direction.”

India would also require putting similar effective systems in place for a robust, ongoing and time-bound review process for its NLEM.

Immense health and economic impact of ‘Essential Medicines’:

Globally the health and economic impact of ‘Essential Medicines’ have been proved to be remarkable, especially in the developing countries, as such drugs are one of the most cost-effective elements in healthcare system of any time. That’s why the stakeholders bestow so much of importance on a well thought out and properly crafted list of essential medicines by the astute experts appointed by the Government.

According to W.H.O, while spending on pharmaceuticals represents less than one-fifth of total public and private health spending in most developed countries, it represents 15 to 30 percent of health spending in transitional economies and 25 to 66 percent in developing countries.

In developing countries, such as India, pharmaceuticals are the largest Out of Pocket (OoP) household health expenditure. “And the expense of serious family illness, including drugs, is a major cause of household impoverishment.”

Flawed NLEM could multiply access to medicines problems:

Despite well-documented global evidence regarding high potential of health and economic impact of ‘Essential Drugs’, if the NLEM does not include right kind of drugs and remains flawed, it could have significant adverse impact on the overall access to ‘Essential Medicines’ in India.

In addition, properly structured NLEM could help setting the right course in the procurement and supply of medicines in the public sector – national or state Government schemes that reimburse medicine costs, and also for domestic production of drugs in the country.

A quick overview of NLEM in India:

There was no functional NLEM in India before 2002. According to a paper titled “Decisions on WHO’s essential medicines need more scrutiny”, published in the BMJ on July 31, 2014, in India the first National Essential Medical List (NEML) was prepared in 1996. However, this list was neither implemented for procuring drugs nor were STGs drawn up.

It all started in 2002, when the National Drug Policy of India, announced in that year, was subsequently challenged through a Public Interest Litigation (PIL) in the Karnataka High Court on the ground of being inflationary in nature. The Honorable Court by its order dated November 12, 2002 issued a stay on the implementation of that Policy.

This judgment was challenged by the Government in the Supreme Court, which vacated the stay vide its order dated March 10, 2003 and ordered as follows:

“We suspend the operation of the order to the extent it directs that the Policy dated February 15, 2002 shall not be implemented. However we direct that the petitioner shall consider and formulate appropriate criteria for ensuring essential and lifesaving drugs not to fall out of the price control and further directed to review drugs, which are essential and lifesaving in nature till 2nd May, 2003”.

As a result DPCO 1995 continued to remain operational, pending formulation of a new drug policy, based on NLEM based span of price control, as directed by the Honorable Supreme Court of India. Necessitated by this directive of the Apex Court of the country, the first NLEM of India came into effect in 2002.

In 2011, NLEM 2002 was subsequently reviewed and re-evaluated by a committee of 87 experts from various fields, and was replaced by the NLEM 2011 with 348 drugs.

In the recent years, following a series of protracted judicial and executive activities, the National Pharmaceutical Pricing Policy 2012 (NPPP 2012) came into effect on December 7, 2012. In the new policy the span of price control was changed to all drugs falling under the National List of Essential Medicines 2011 (NLEM 2011) and the price control methodology was modified from the cost-based to market based one. Accordingly the new Drug Price Control Order (DPCO 2013) was notified on May 15, 2013.

However, the matter is still subjudice, as NPPP 2012 would ultimately require passing the acid test of scrutiny by the Supreme Court of India, in the future days.

A recent study emphasizes need for urgent expansion of NLEM:

A March 2015 independent evaluation of DPCO 2013, which controls prices of essential medicines in India as featured in the NLEM 2011, brought to light some interesting facts. The Public Health Foundation of India (PHFI) and the Institute for Studies in Industrial Development released this report titled “Pharmaceutical Policies in India: Balancing Industrial and Public Health Interests” at a conference on pharmaceutical policies in India, held in New Delhi from 3 to 7 March, 2015.

This independent evaluation would most probably be submitted to the Supreme Court where PHFI is one of the petitioners in a case challenging the current NPPP 2012.

The study found that price regulations of NLEM 2011 are limited to just 17 percent of the total pharmaceutical market in India. This leaves 83 percent of the domestic pharma market free from price control, providing only marginal financial relief to patients for all essential medicines, in its true sense, as desired by the Supreme Court of India. Thus, one of the key recommendations of this study is to review the NLEM 2011, urgently.

“Clearly the interests of the pharmaceutical industry have received precedence over the interest of the patient population,” the report highlighted.

Anurag Bhargava, of the Himalayan Institute of Medical Sciences, was quoted in March 2014 BMJ Article titled, “Analysts in India call for urgent expansion of essential medicines list”, saying:

“This is a matter of concern given that the NLEM was not drafted as an instrument for price regulation. It is a representative rather than a comprehensive list of medicines utilized in actual practice. To serve as a reference for rational prescribing, the NLEM includes only a few model dosage forms, strengths, and combinations of drugs.”

NLEM 2011 fails to reflect public health priorities:

The report, with relevant details, brings to the fore that NLEM 2011 has failed to reflect India’s public health priorities. It underscores the following glaring deficiencies in NLEM 2011, which covers just:

  • 1 percent of drugs for anemia
  • 5 percent of respiratory drugs
  • 7 percent of antidepressants
  • 15 percent of drugs for diabetes
  • 18 percent of drugs for tuberculosis
  • 13 percent of anti-malarial drugs
  • 23 percent of cardiac drugs
  • 35 percent of antibiotics

Areas for revision in NLEM 2011:

A critical appraisal of NLEM 2011 was done in the above-mentioned 2014 BMJ paper and also by the NPPA separately.

Taking all these into consideration, some key areas of concerns related to NLEM 2011 floats at the top of mind. A few examples of important issues, which need immediate attention, are as follows (not necessarily in the same order):

  • Other key strengths and dosage forms of the same drugs covered under NLEM 2011
  • Analogues of scheduled formulations not covered
  • Close substitutes in the same therapeutic class not covered
  • Some essential drugs listed in the W.H.O model list and even in Delhi list are missing in the NLEM 2011
  • Several essential HIV and Cancer drugs are not included in NLEM 2011
  • Essential oral anti-diabetic medicines, like glimeperide and glicazide do not find place in NLEM 2011, especially when the list in the DSPRUD for Delhi includes anti-diabetic medicines such as glimepiride, sitagliptin, vildagliptin, saxagliptin
  • Commonly used anti-asthmatic medicines like almeterol and montelukast are missing in NLEM 2011
  • When W.H.O model List (EML) includes capreomycin, cycloserine, ethionamide, kanamycin and para-aminosalicylic acid for treatment of multi-drug resistant tuberculosis, these drugs are missing in NLEM 2011 list
  • Though a large number of Fixed Dose Combinations (FDCs) are prescribed to treat common ailments in India, especially in certain therapeutic groups such as respiratory, cardiovascular, anti-diabetic, dermatology, anti-malarial and anti TB/MDR TB, most of these are missing in NLEM 2011
  • While the W.H.O list mentions 21 vaccines, the NLEM 2011 mentions only nine vaccines
  • A separate list of lifesaving drugs based on existing lifesaving drugs list of government agencies like the CGHS needs to be worked out
  • Pediatric formulations need to be included in NLEM
  • Inclusion of some medical devices which are already covered under the definition of drugs under the Drugs and Cosmetics Act 1940
  • Essential and well-selected lifesaving patented drugs should also feature in the NLEM, just as what W.H.O has done this month by adding to its ‘Essential Medicines List’ all the five patented new curative treatments for hepatitis C, besides 16 new cancer drugs.

Thus, in its present form the NLEM 2011 needs a critical relook and revision, mainly in the light of the missing drugs and keeping in view of the requirements under various National Health Programs as well as the National Formulary of India 2010.

The BMJ paper also highlights, the Indian Academy of Pediatrics has come out with a list of ‘Essential Drugs’ for children in India. Such a list might be consulted for the Pediatric List of Essential Medicine within the NLEM. Provision should be made to review the NLEM at two yearly intervals, as is currently practiced by the W.H.O.

Civil Society steps in:

Accordingly, in August 2014, seven Civil Society Organizations in a letter to Minister Ananth Kumar with a copy to Prime Minister Narendra Modi, among others, wrote as follows:

“Limiting all price regulation only to a list of 348 medicines and specified dosages and strengths in the DPCO 2013 goes against the policy objective of making medicines affordable to the public. The National List of Essential Medicines, a list of 348 rational and cost-effective medicines, is not the basis for production, promotion and prescription in India. In reality the most frequently prescribed and consumed medicines are not listed in the NLEM.”

Healthcare: China on a fast track, India crawls through a slow lane: 

Interestingly, to help improve economic growth and boost domestic consumption, China has recently decided to floor the gas pedal on the fast lane of healthcare reform, while India chose to continue to crawl through its slow lane.

Interestingly, both the countries want to draw similar sets of trend lines for health and economic progress of their respective nations.

This has been vindicated by Reuters report of May 9, 2015, when it highlighted, China would increase its healthcare subsidies by 19 percent this year as part of efforts to deepen social reforms and strengthen safety nets.

The report also indicated, economists view this measure as crucial for China to improve the quality of its healthcare, if it wishes to remake its economy and boost domestic consumption. They say a stronger safety net will encourage Chinese to spend more and save less.

As opposed to the Chinese scenario, in India, the Union Budget 2015-16 came as a real dampener for the healthcare space in the country. This assumes greater significance, as the budget was planned by the reform oriented Modi Government.

Despite the dismal state of current public healthcare services, the annual budgetary allocation for healthcare has been kept at Rs. 33,152 Crore, just a tad more than Rs. 30,645 Crore of 2014-15, with no visible indication for any healthcare reform measure in the country, any time soon.

Conclusion:

‘Essential Medicines’ based drug price control, as was directed by the Honorable Supreme Court of India, is just not far sighted, but a potential game changer in the healthcare space of the country.

While looking at the bigger picture, this policy also promises a significant contribution in the overall economic progress of the nation.

To make this policy effective in the longer term, NLEM should be fair, impartial, far sighted, up to date, robust and beyond obvious any controversy, which includes its authors… just as the spirit behind the good old saying: “Caesar’s wife must be above suspicion.”

Unfortunately, NLEM 2011 is mired with many shortcomings for all the wrong reasons, as discussed above.

The incumbent Government would require striking a just and right balance between public health interest and expectations of the Pharma industry in this critical area. Taking the right policy decision in a transparent an effective manner, balancing the healthcare and economic interest of the country, would be critical.

That said, Pharma industry in India, I reckon, would also not be devastatingly impacted with the possible expansion of NLEM. This is mainly because, currently only 17 percent of the total pharmaceutical market in India comes under price control, based on the span of NLEM 2011 formulations. In any case, the balance 83 percent of the domestic pharma market still falls under the free-pricing zone.

Even when DPCO 1995 came into force, which continued till DPCO 2013 became effective, 20 percent of the total domestic pharmaceutical market was under price control.

Moreover, there was no provision for automatic annual price increases for price-controlled drugs under DPCO 1995. Whereas DPCO 2013 has a provision for annual price increases for all such essential drugs based on WPI. As a result, MRPs of all price controlled essential drugs have gone up effective April 1 of this year and would continue to happen so every year, as long as NPPP 2012 remains in force.

Under this complex mosaic and fast evolving backdrop, the announcement of the Union Minister for Chemicals and Fertilizers – Mr. Ananth Kumar on the floor of the Parliament last week is a laudable one.

To help improve access to affordable essential medicines for all in the country, the Minister has reiterated, “The expanded NLEM would bring more essential drugs under price control.”  This categorical affirmation by the Government in power, though belated, is a step in the right direction…for both better healthcare and also its consequential critical impact on the economic progress of India.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Pharma & Healthcare: Where The Healers Turn Looters?

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Two news reports of the last week, though no longer shocking, made me think exactly the same way as the headline of this article epitomizes.

These reports are not just two isolated instances, but an integral part of a similar chain of events that I partly addressed in one of my earlier blog posts titled, “Is The Core Purpose of Pharma Business Much Beyond Profit Making?” of November 10, 2014.

With the fist clenching media reports of just the last week, I shall try to dwell upon that in absence of good governance how two of the greatest healers and the medical care givers in the arena of healthcare – the doctors and the hospitals, are being increasingly perceived by the common citizens as nothing less than looters.

The doctors:

A November 21, 2014 report highlights that the Medical Council of India (MCI) has summoned over three hundred doctors from various parts of India, based on an anonymous complaint, for taking lakhs of rupees as bribes from an Ahmedabad based pharmaceutical company. All those 300 doctors have been told to bring copies of their Income Tax returns and bank statements.

Just a year ago, in September 2013, the Chief Vigilance Commissioner reportedly received a letter alleging that doctors were taking bribes from Pharma companies. The complaint was forwarded to the Health ministry. The MCI took over the case in December 2013 and formed a subcommittee to investigate the doctors.

The complaint details that the Ahmedabad-based pharma company has been paying to the doctors not just huge cash, but also gifting them cars and flats, besides sponsoring foreign trips for the family.

In return, the involved doctors are allegedly prescribing that Ahmedabad based pharma company’s products that are priced 15 to 30 percent higher than those of well-established other pharma players.

In addition, according to reports, the doctors would also air on the Television sets placed at their respective clinics, advertisements of the pharma company products against hefty cash or equivalent in kind.

Although, the allegations of unholy nexus between pharma players and the doctors are continuity of a good old saga, the risk taking incentives that it provides to the wrong doers are very significant. The anonymous letter alleged that the concerned pharma company’s profit zoomed from zero to Rs. 400 Crore in a period of just 5 years.

According to available reports, the MCI has already questioned 166 doctors, out of which 7 are senior doctors from Maharashtra, including 3 physicians from Mumbai.

The hospital:

Another report on the subject that appeared yesterday is related to overcharging for an oncology medicine of Novartis – Sandostatin LAR, over the last nine months by the well-known Tata Memorial Hospital of Mumbai.

According to the report, even when Novartis revised the price of Sandostatin LAR from Rs. 65,499 for a 20mg vial to Rs 32,000 during Oct-Dec 2013 and the chemists in the hospital’s vicinity were selling the same vial for Rs 32,000, Tata Memorial continued to sell it at Rs 48,296.

The report also states that patients could have saved much more, if the hospital had prescribed an Octreotide generic of the same strength, Octride Depot 20mg by Sun Pharma with an MRP of Rs 17,800 is sold at Tata Memorial for Rs 12,157, instead of Sandostatin LAR 20mg.

However, the newspaper claims, “DNA was the first to report about the price disparity at the hospital on Nov 5. Tata Memorial Hospital has decided to reimburse cancer patients who were overcharged for a Novartis-branded oncology medicine over the last nine months.”

Interestingly, we get to know only about a few of such instances, only when these are reported either anonymously or by some employees or through rare impartial investigative journalism of international standard.

Treatment of dreaded diseases like Cancer also not spared:

The above hospital case assumes immense importance, as it is related to a dreaded disease and an expensive cancer drug. In real every day life, many such cases of various hues and colors are taking place in India incognito, at the cost of patients.

A scary scenario:

According to the ‘Fact-Sheet 2014′ of the World Health Organization (WHO), cancer cases would rise from 14 million in 2012 to 22 million within the next two decades. It is, therefore, no wonder that cancers figured among the leading causes of over 8.2 million deaths in 2012, worldwide.

A reflection of this scary scenario can also be visualized while analyzing the growth trend of various therapy segments of the global pharmaceutical market.

A recent report of ‘Evaluate Pharma (EP)’ has estimated that the worldwide sales of prescription drugs would reach US$ 1,017 Bn. by 2020 with a Compounded Annual Growth Rate (CAGR) of 5.1 percent between 2013 and 2020.

Interestingly, oncology is set to record the highest sales growth among the major therapy categories with a CAGR of 11.2 percent during this period, accounting for US$ 153.4 Bn. of the global pharmaceutical sales.

High incidence of cancer in India:

A major report published in ‘The Lancet Oncology’ states that in India, around 1 million new cancer cases are diagnosed each year, which is estimated to reach 1.7 million in 2035.

The report also highlights, though deaths from cancer are currently 600,000 -700,000 annually, it is expected to increase to around 1.2 million during this period.

The Lancet Oncology study showed, while incidence of cancer in the Indian population is only about a quarter of that in the United States or Europe, mortality rates among those diagnosed with the disease are much higher.

Experts do indicate that one of the main barriers of cancer care is its high treatment cost that is out of reach for millions of Indians.

Breast cancer is the most common type of cancer, accounting for over 1 in 5 of all deaths from cancer in women, while 40 percent of cancer cases in the country are attributable to tobacco.

Cancer drug price – a global issue to address:

As the targeted therapies have significantly increased their share of global oncology sales, from 11 percent a decade ago to 46 percent last year, increasingly, both the Governments and the payers, almost all over the world, have started feeling quite uncomfortable with the rapidly ascending drug price trend.

In the top cancer markets of the world, such as, the United States and Europe, both the respective governments and also the private insurers have now started playing hardball with the cancer drugs manufacturers.

There are several instances in the developed markets, where the stakeholders, such as, National Institute for Health and Care Excellence (NICE) of the United Kingdom and American Society of Clinical Oncology (ASCO) are expressing their concerns about manufacturers’ charging astronomical prices, even for small improvements in the survival time.

Following examples would give an idea of global sensitivity in this area:

After rejecting Roche’s breast cancer drug Kadcyla as too expensive, NICE reportedly articulated in its statement: “A breast cancer treatment that can cost more than US$151,000 per patient is not effective enough to justify the price the NHS is being asked to pay.”

In October 2012, three doctors at Memorial Sloan-Kettering Cancer Center announced in the New York Times that their hospital wouldn’t be using Zaltrap. These oncologists did not consider the drug worth its price. They questioned, why prescribe the far more expensive Zaltrap? Almost immediately thereafter, coming under intense stakeholder pressure Sanofi reportedly announced 50 percent off on Zaltrap price.

Similarly, ASCO in the United States has reportedly launched an initiative to rate cancer drugs not just on their efficacy and side effects, but prices as well.

Developments in India:

India has already demonstrated its initial concern on this critical issue by granting Compulsory License (CL) to the local player Natco to formulate the generic version of Bayer’s kidney cancer drug Nexavar and make it available to the patients at a fraction of the originator’s price. As rumors are doing the rounds, probably some more patented cancer drugs would come under Government scrutiny to achieve the same end goal.

I indicated in my earlier blog post that the National Pharmaceutical Pricing Authority (NPPA) of India by its notification dated July 10, 2014 has decided to bring, among others, some anticancer drugs too, not featuring in the National List of Essential Medicines 2011 (NLEM 2011), under price control. These prices have already in force.

Not too long ago, the Indian government reportedly contemplated to allow production of cheaper generic versions of breast cancer drug Herceptin in India. Roche – the originator of the drug ultimately surrendered its patent rights in 2013, apprehending that it would lose a legal contest in Indian courts, according to media reports.

Biocon and Mylan thereafter came out with biosimilar version of Herceptin in the country with around 40 percent lesser price.Herceptin,

Hence, affordable pricing of cancer drugs would continue to remain a key pressure point, as it just happened yet again.

The government to intervene again:

According to a media report of the last week, the new government in India is planning to control prices of anti-cancer drugs to address this critical issue.

As the current National List of Essential Medicines (NLEM) does not include many important anti-cancer medication, Tata Memorial Centre of Mumbai has recommended to the government that oncology drugs, such as Trastuzumab, Erlotinib, Irinotecan, Lenalidomide, Capecitabine, All Trans Retinoic Acid (ATRA), Bendamustine, Rituximab, Temozolomide (TMZ), Zoledronic acid, Megestrol acetate and Letrozole, should be added to the NLEM.

As a first step towards this direction the National Pharmaceutical Pricing Authority (NPPA) has invited comments on the same from the pharmaceutical industry and other stakeholders to bring these drugs under price control.

Quoting NPPA the report states, “the recommendations are based on factors such as the ability of the drug to improve the overall survival chances of the patient. The other factors include higher priority to drugs that have the potential to cure a fraction of patients versus those that have been proven to only prolong lives; the number of patients potentially impacted in India based on data from population based cancer registries of the National Cancer Registry Program; the non-availability of alternative medications of the same or other pharmacological class that can act as a reasonable ‘substitute’; and price of the drug to patients and the differential in price between various brands.”

Although this is a welcome move to most of the patients, the pharma industry would certainly not be happy with this development, because of very obvious reasons and is expected to strongly oppose this initiative of the government. Let us wait and watch how this scenario unfolds further.

Conclusion:

In pursuit of the Eldorado to generate more and more wealth, shorn of least concerns for majority of patients, quite a few companies are not sparing even the dreaded diseases, such as cancer, pushing many patients to abject poverty, if not untimely death.

Increasingly, many healthcare players across the world are reportedly being forced to pay heavily for ‘unethical behavior and business practices’ by the respective governments. Unfortunately, no such steps are being taken in India, not just yet.

At least on paper, for errant doctors and hospitals there is MCI to take prompt remedial measures. For implementation of Drug Price Control Order (DPCO) there is NPPA, though effectiveness of these two seemingly powerful bodies are far from the expectations of the stakeholders, occasional reported jingoism notwithstanding.

Currently in India, there are no legally binding ‘codes of pharma marketing practices’ in place. Even the Department of Pharmaceutical does not seem to have any legal jurisdiction for taking penal action against the errant pharma players for marketing malpractices or misdemeanor.

In this chaotic scenario, is it not quite challenging to fathom how would the government possibly discourage any healthcare or pharma player from turning looter instead of playing the expected role of a healer, ensuring beyond doubt that there is no wolf in sheep’s clothing?

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.