Tag Archives: medicine

On Serious Healthcare, Some Bizarre Decisions

Posted on by
Reply

On August 04, 2016, it was widely reported by the media that the Union Minister of Chemicals and Fertilizers – Mr. Anant Kumar, would launch a new digital initiative of the National Pharmaceutical Pricing Authority (NPPA), named, “Search Medicine Price”, on August 29, 2016.

This is an app developed by the National Informatics Centre, for android smartphones ‘that will enable patients to check the prices of essential medicines on-the-go’. It will be an extension of NPPA’s “Pharma Jan Samadhan” web-portal facility. The Indian price regulator believes that wide use of this app would successfully reduce the instances of overcharging the consumers by the pharma companies and retail chemists, especially for lifesaving, and other expensive medicines. 

India’s drug pricing watchdog is planning to introduce this app to enable the patients check the prices of essential medicines on-the-go, and expects that this measure will hold drug companies and medicine retail outlets more accountable to patients.

In the test version of the app, which has since been released for stakeholder feedback, patients can search for the ceiling price of all medicines under the National List of Essential Medicines (NLEM), on the basis of its generic name and the state they’re buying it from.

The Chairman of NPPA, reportedly, further said, “Consumers can use the app before paying for a medicine to ensure that they get the right price. At present, whatever action we take against the companies, including recoveries, the consumer does not get back the overcharged amount he or she has paid.”

Good intent with a basic flaw:

The intent of the Government in this regard is indeed laudable. However, the initiative seems to underscore the blissful ignorance of the prevailing ground realities in India.

The media report highlights that with this app, the patients can search for the ceiling price of all medicines featuring in the NLEM on the basis of their generic names.

Whereas, the ground reality to make any meaningful use of this app is quite different. This is primarily because, in the Indian Pharmaceutical Market (IPM), over 90 percent of drugs are branded generics. An overwhelming majority of the doctors, as well, follow this trend while writing prescriptions for their patients, in general. For any single ingredients or Fixed Dose Combination (FDC) formulation, there are as many as even 30 to 40 brands, if not more. 

In that case, when the prescriptions given to patients are mostly for branded generic drugs, how would that person possibly get to know their generic names, to be able to check their ceiling prices with the help of the new “Search Medicine Price” app?

Not just a solitary example: 

This is just not a solitary instance of ignorance of the Government decision makers on the realities prevailing in the country.

With an admirable intent of making drugs more affordable for increased access, especially, to all those patients incurring out-of-pocket health expenditure, the Government has been taking several such measures, and is also trying to create a hype around these. Unfortunately, most of these efforts, miss the core objective of increasing access to drugs at the right price, by miles. 

Another recent example: 

This particular example, in my view, is even more bizarre.

It happened on February 29, 2016, the day when the Union Budget proposal for the financial year 2016-17 was presented before the Parliament of India.

In this budget proposal, the Union Finance Minister announced the launch of ‘Pradhan Mantri Jan-Aushadhi Yojana (PMJAY)’. 3,000 Stores under PMJAY will be opened during 2016-17.

Many consider this scheme as a repackaged old health care initiative, only adding the new words ‘Pradhan Mantri’ to it.

Just to recapitulate, Jan-Aushadhi is an ongoing campaign launched by the Department of Pharmaceuticals in 2008, in association with Central Pharma Public Sector Undertakings (PSU), to provide quality medicines at affordable prices to the masses.

Under this scheme, Jan Aushadhi Stores (JAS) are being set up to provide generic drugs, which are available at lesser prices, but are equivalent in quality and efficacy as expensive branded drugs.

The Department of Pharmaceuticals had initially proposed to open at least one JAS in each of the 630 districts of the country, so that the benefit of “quality medicines at affordable prices” is available to at least one place in each district of India.

If the initiative becomes successful, based on its inherent merit and the cooperation of all stakeholders, the scheme was to be extended to sub divisional levels as well as major towns and village centers by 2012. However, after 5 years, i.e. up to February, 2013, only 147 JAS were opened, and out of those only 84 JASs are functional. 

More recently, according to a June 02, 2015 report, “under the new business plan approved in August 2013, a target of opening 3,000 Jan Aushadhi stores during the 12th plan period i.e. from 2013-14 to 2016-17 was fixed. As per the Standing Committee on Chemicals and Fertilizers report in March 2015, till date only 170 JAS have been opened, of which only 99 are functional.”

Tardy progress:

The tardy progress of the scheme was largely attributed to:

  • A lackluster approach of State governments
  • Poor adherence to prescription of generic drugs by doctors,
  • Managerial/ implementation failures of CPSU/ BPPI.
  • Only 85 medicines spread across 11 therapeutic categories were supplied to the stores and the mean availability of these drugs was found to be 33.45 percent, with wide variations across therapeutic categories. 

There is no doubt, however, the intent of ‘Pradhan Mantri Jan-Aushadhi Scheme’ of 2016 is as laudable as the earlier “Jan-Aushadhi Scheme”, launched by the Department of Pharmaceuticals in 2008, was at that time. But, the moot question that comes at the top of mind:  Is it robust enough to work effectively in the present situation? 

Why it may not fetch the desired outcome?

Besides strong support from the State Governments, and other factors as enlisted above, making the doctors prescribe drugs in generic names would be a critical issue to make the “Pradhan Mantri Jan-Aushadhi scheme’ a success, primarily to extend desirable benefits to a sizeable section of both the urban and rural poor. Another relevant question that comes up now, how would the Government ensure that the doctors prescribe drugs in the generic names?

A critical challenge:  

Since, the generic drugs available from ‘Jan Aushadhi’ retail outlets are predominantly prescription medicines, patients would necessarily require a doctor’s physical prescription to buy those products.

Despite some State Government’s circulars to the Government doctors for generic prescription, and the Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, that states: “Every physician should, as far as possible, prescribe drugs with generic names and he/she shall ensure that there is a rational prescription and use of drugs”, the doctors, in India, prescribe mostly branded generics. It includes even many of those prescriptions, generated from a large number of the Government hospitals.

The legal hurdle for generic substitution:

In a situation such as this, the only way the JAS can sell more for greater patient access to essential drugs, if the store pharmacists are allowed to substitute a high price branded generic with exactly the same generic molecule that is available in the JAS, without carrying any brand name, but in the same dosage form and strength, just as the branded ones. 

However, this type of substitution would be grossly illegal in India. This is because, the section 65(11)(c) in the Drugs and Cosmetics Rules, 1945 states as follows:

“At the time of dispensing there must be noted on the prescription above the signature of the prescriber the name and address of the seller and the date on which the prescription is dispensed. 20[(11A) No person dispensing a prescription containing substances specified in 21[Schedule H or X] may supply any other preparation, whether containing the same substances or not in lieu thereof.]” 

Thus, I reckon, the most important way to make ‘Jan Aushadhi’ drugs available to patients for greater access, is to legally allow the retailers substituting the higher priced branded generic molecules with their lower priced equivalents, sans any brand name.

A move that did not work:

Moving towards this direction, the Ministry of Health had reportedly submitted a proposal to the Drug Technical Advisory Board (DTAB) to the Drug Controller General of India (DCGI), for consideration.

In this proposal, the Health Ministry reportedly suggested an amendment of Rule 65 of the Drugs and Cosmetics Rules, 1945 to enable the retail chemists substituting a branded drug formulation with its cheaper equivalent, containing the same generic ingredient, in the same strength and the dosage form, with or without a brand name.

However, in the 71st meeting of the DTAB held on May 13, 2016, its members reportedly turned down that proposal of the ministry. DTAB apparently felt that given the structure of the Indian retail pharmaceutical market, the practical impact of this recommendation may be limited.

Conclusion:

Considering all this, just as ‘Pradhan Mantri Jan Aushadhi Yojana’, the likes of ‘Search Medicine Price app’, apparently, are not potentially productive health care related initiatives, if not just one-offs, ‘feel good’ type of schemes for the general population. 

These are not robust enough either, to survive the grueling of reality, impractical for effective implementation, and thus, seriously handicapped to fetch any meaningful benefits for the patients, on the ground.

It is, therefore, still unclear to me, how would the needy patients, and the Indian population at large, could derive any benefit from such bizarre decisions, on so serious a subject as 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.

How Expensive Is Drug Innovation?

Posted on by
Reply

High prices for patented drugs are quite often attributed to the exorbitant cost of drug innovation, by the global pharma players. This argument is played, replayed again, again… and again by them, in various ways and forms, especially when many eyebrows are raised, failing to fathom the primary reason for ever escalating prices of life-saving new drugs.       

I find the same argument often getting echoed by some section of both the global and local media too, and also through some cleverly disguised and apparently sponsored articles on the subject. 

In this article I shall dwell on this sensitive issue.

A strong justification: 

The Institute for Policy Innovation (IPI) based in Texas in the United States, in an article titled “The High Cost of Inventing New Drugs–And of Not Inventing Them”, published on April 16, 2015 reiterated that the financial cost of developing new drugs is indeed a big one.

It argues that “there is also a big cost to not developing new drugs, and that cost can be both financial and human. People may be able to live with the pain that an undiscovered drug might have alleviated, but they may not be able to do all the things they would have.”

The paper asks, “A cancer patient might still have a few productive years after a diagnosis, but how much would it be worth to the patient—and to society (think Steve Jobs), if a new drug could extend a patient’s life indefinitely?”

“The drug manufacturers poured money into finding a treatment for AIDS once it became clear the disease would take thousands of lives. The research and development was costly and didn’t emerge overnight, but being diagnosed with AIDS is no longer a death sentence,” the authors elucidated.

This is a very cogent argument, and nobody would dispute it. This issue lies somewhere else, as I would try to explore in this article.

The supporting data: 

We also find supporting published data to justify the high cost of innovation with numbers.

On November 18, 2014, a new study by the ‘Tufts Center for the Study of Drug Development’ highlighted that developing a new prescription medicine and gaining its marketing approval, which is a process often lasting longer than a decade, is estimated to cost US$ 2,558 million.” This number is indeed mind boggling by any yardstick.

While many details of the study remain a secret, only slightly more than half of this cost is directly related to research and development (R&D). For example, US$ 1.2 billion are “time costs” – returns that investors might have made if their money wasn’t tied up in developing a particular drug.

Not many takers:

Besides the above reason, for several other factors, there does not seem to be many takers for this exorbitant cost of innovation and bringing a new drug to the market.

The above study has become a contentious one and has, therefore, been challenged by many experts. I would give here just one example, out of many, from a highly credible source.

May 14, 2015 issue of ‘The New England Journal of Medicine’ questioned the methods used to generate the US $ 2.6 billion figure and raised the following interesting points in the above Tufts Center study: 

  • The analysis was based on data that 10 unnamed drug makers provided on 106 unnamed investigational compounds that they had “self-originated.”
  • The raw numbers on which the analysis is based are not available for transparent review, and are likely never to be divulged. 
  • Since a balanced assessment would have to take into account the costs of failures as well as successes, it is hard to evaluate the key assumption that more than 80 percent of new compounds are abandoned at some point during their development, which is a key driver of the findings.
  • Nearly half the total cost of developing a new drug (US$ 1.2 billion) was ascribed to this cost of capital, with only US$ 1.4 billion attributed to the funds actually spent on research. These capital costs were assessed at 10.6 percent per year, compounded, despite the fact that bonds issued by drug companies often pay only 1 to 5 percent.
  • In terms of access to capital, it’s interesting to note that large drug makers are among the U.S. firms with the highest amounts of profits held overseas. Two pharmaceutical companies are ranked third and fourth among all the U.S. corporations in this regard: Pfizer (US$ 69 billion) and Merck (US$ 57 billion), respectively. Collectively, another eight drug companies reportedly have an additional US$ 173 billion of capital that is retained overseas, untaxed by the United States. Such funds could potentially help with the cash-flow problem that plays such a large role in these estimated costs of drug development.
  • The Tufts calculations also explicitly do not take into account the large public subsidies provided to pharmaceutical companies in the form of research-and-development tax credits or substantial payments received from the federal government for other research activities, such as testing their products in children. 
  • The US$ 2.6 billion figure does not consider drug-development costs borne by the public for the large number of medications that are based on external research that elucidated the disease mechanisms they address.
  • One recent analysis showed that more than half of the most transformative drugs developed in recent decades had their origins in publicly funded research at nonprofit, university-affiliated centers.
High innovation cost fails to justify high drug prices:

That even the high cost of innovation fails to justify high drug prices, was also echoed in an article published in ‘The New York Times’ on December 19, 2015.

The article categorically said, ‘there is ample evidence that drug prices have been pushed to astronomical heights for no reason other than the desire of drug makers to maximize profits. Prices in many cases far exceed what’s needed to cover the costs of research and clinical trials, and some companies have found ways to rake in profits even without shouldering the cost of drug development.’

Yet another justification of high new drug prices:

Yet another justification of a slightly different kind also frequently comes from the global pharma players for high prices of new drugs.

On May 2, 2015 ‘The Washington Post’ also published an article, which recapitulated this oft repeated justifications for keeping the prices of new drugs high, especially those for rare diseases, including many types of cancer. The key rationale of this argument: the smaller is the number of patients who need the drugs, more would be the need of the company to price the drugs high to recoup the significant costs of drug development.

On the face of it, this justification too may sound convincing. However, on the ground, even if this argument of the global drug companies fails to stand on its feet, post robust scrutiny of the experts. In that context, I shall cite two recent examples.

Two new research studies broke this myth too:

The Following two April 2016 study conclusively demolishes the above justification of the global drug companies:

1. On April 28 2016, a new study was published in  JAMA Oncology, throwing  a great deal of light on the robustness of the above reasoning. In this paper, the researchers looked at 32 oral cancer medications and found that launch prices of these drugs have spiraled upward, even after adjusting for inflation. The average monthly amount insurers and patients paid for a new cancer drug was less than US$ 2,000 in the year 2000, but it skyrocketed to US$ 11,325 in 2014. 

2. In April 2016, another study published in Health Affairs found, when a drug became useful to a larger number of patients, the price also shot up. It, therefore, concluded as follows:            

“Our findings suggest that there is currently little competitive pressure in the oral anticancer drug market. Policy makers who wish to reduce the costs of anticancer drugs should consider implementing policies that affect prices not only at launch but also later.”              

Are high new drug prices, then arbitrary?

According to a July 2015 article published in JAMA Oncology, the high prices of new drugs, especially for cancer, are arbitrary. This is vindicated in the discussion of the article that clearly states, as follows: 

“Cancer drug prices are rising faster than the prices in other sectors of health care, drawing concern from patients, physicians, and policy researchers. We found little difference in the median wholesale price of 21 novel drugs and 30 next-in-class drugs approved over a 5-year period (next-in-class drugs, $119 765; novel drugs, $116 100; P = .42).”

“Our results suggest that the price of cancer drugs is independent of novelty. Additionally, we found little difference in price among drugs approved based on time-to-event end points and drugs approved on the basis of RR (disease Response Rate). Our results suggest that current pricing models are not rational, but simply reflect what the market will bear.” 

Thus, the derived fact is, the high prices of new drugs are neither dependent on high cost of drug innovation, nor on the number of drug users – high or low. Higher drug prices, therefore, appear to be nothing but arbitrary, the public justifications being no more than façades. 

Is the real cost of drug innovation much less?

This question brings me back to the moot point, ‘What is then the real financial cost of drug innovation?’

The search for a generally acceptable answer to this question gets even more complicated, when one reads the paper of The Bureau of Economics, Federal Trade Commission’ in Washington, DC, published on March 7, 2006 in Health Affairs – the leading journal of health policy thought and research.

The paper estimates the cost per new drug to be US US$ 868 million. However, it says, “Our estimates vary from around US$ 500 million to more than US$ 2,000 million, depending on the therapy or the developing firm. The paper recommended that variations in cost estimates suggest that policymakers should not use a single number to characterize drug costs.

Conclusion:

This situation arises, because the drugs with brand names, whether patented or off-patent, do not compete on price in the pharma market, across the world. The primary reason being a consumer is neither the prescription decision makers nor can they exercise their brand choice in any manner. For any patients, a doctor always takes this decision, who is often influenced by the drug manufacturers, and may not be even aware of the drug price, as is generally alleged, globally.

This process is quite unlike to any other essential commodities. However, the ongoing marketing campaigns for branded drugs are quite a keen to commonly used consumer goods, carrying brand names and backed by high profile branding campaigns, where high prices rather add greater perceived value to the brand status.

But the irony is glaring. The administration of life-saving highly expensive drugs is not optional for any patient, whether poor or rich. These are necessary to save lives. Thus, does not merit arbitrary high-profit driven pricing, at least, from the standpoint of patient-centric ethical business practices.

It still happens, even at the cost of access to such drugs by a large majority of the global population, who requires them the most. In all probability, this process is likely to continue in the near future too, irrespective of the quest of many to fathom how expensive is the drug innovation, unless the government or other payers actively intervenes. I shall discuss this issue in my next article in this Blog. 

Nevertheless, the answer to the crucial question, ‘How expensive is the drug innovation’ would continue to remain elusive to many, at least in the near term. This because, no global drug company is likely to allow any competent and independent experts group to arrive at this number in a transparent manner, which can also be peer reviewed. Nor would the pharma players, in all probability, furnish this information to any Government to justify the high price of their respective new brands.

Till this is done, pricing decisions of new lifesaving drugs would continue to remain arbitrary, primarily driven by high-profit motives. It is unlikely to have even a remote direct linkage to the cost of drug innovation, limited consumer access notwithstanding, just as what happens with many branded consumer goods.

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.

 

‘Indian Drug Control World’s Weakest: Pharma Trade Bodies Working At Cross Purposes’

Posted on by
Reply

“In the entire world, I think our drug control system probably is the weakest today. It needs to be strengthened,” said the Secretary of the Department of Pharmaceuticals (DoP) – V K Subburaj at an event in New-Delhi on April 19, 2016. 

In his speech, the Secretary also singled out the pharma industry associations for working in opposite directions, adding that “if we take one decision, it is appreciated by one but the other one criticizes us”.

This is indeed an irony. Such scathing comments from an important and a top Government official indeed stand out. This is primarily because, in the midst of the prevailing scenario, where a large section of the Government is saying ‘we are the best’ or ‘best among the worst’ or, at least, ‘fast improving’, a seemingly helpless key decision maker for the pharma industry was constrained to publicly say, what he had said, as above.

Nonetheless, public expressions, such as these, coming from a top Government official well-captures the sad and pathetic scenario of the systemic failure of pharma industry regulators to bring order in the midst of continuing chaos. Virtually free-for-all business practices, blatantly ignoring the patients’ health and safety interest in the country, continue to thrive in a self-created divisive environment.

Unsparing remarks in two critical areas:

As reported by the ‘Press Trust of India (PTI)’, the DoP Secretary, with his unsparing remarks, publicly expressed his anguish for the delay in taking remedial measures, at least in the two critical areas of the pharma industry in India, as follows:

  • Questionable quality of drugs
  • Questionable pharma marketing practices 

He also highlighted, how just not some Government Departments, but the pharma trade associations, which are formed and fully funded by the pharma players, both global and local, are working at cross-purposes to perpetuate the inordinate delay in setting a number of things right, to satisfy the healthcare needs of most patients.

I briefly dwelled on this critical conflict in my article in this blog of March 28, 2016 titled, “Ease of Doing Pharma Business in India: A Kaleidoscopic View”

A. Questionable quality of drugs:

There wasn’t enough debate in the country on the questionable drug quality in India. It began when the US-FDA started banning imports of a number of medicines in the United States from several drug manufacturing facilities in India. These pharma plants are of all sizes and scales of operations – large, medium, small and micro.

Almost on a regular basis, we now get to know, both from the national and international media, one or the other pharma manufacturing facility in the country, has received the ‘warning letter’ from the US-FDA on its ‘import ban’.

Dual drug manufacturing quality standards?                                            

The spate of ‘Warning Letters’ from the US-FDA have brought to the fore the existence of two different quality standards of drug manufacturing in India:

  • High quality plants dedicated to exports in the well-regulated markets of the world, such as, the United States, following the US-FDA regulations.
  • Other plants, with not so stringent quality standards of the Drug Controller General of India (DCGI), cater to the needs of the Indian population and other developing non-regulated markets. 

In this situation, when many Indian manufacturers are repeatedly faltering to meet the USFDA quality standards, the following two critical questions come up:

  • Are the US-FDA manufacturing requirements so stringent that requires a different compliance mindset, high-technology support, greater domain expertise and more financial resources to comply with, basically for protection of health and safety of the American patients?
  • If so, do the Indian and other patients from not so regulated markets of the world, also deserve to consume drugs conforming to the same quality standards and for the same reason? 

Answers to these questions are absolutely vital for all of us.

Pharma associations working at cross-purposes? 

Considering this from the patients’ perspective, there lies a huge scope for the pharma associations, though with different kind of primary business priorities, to help the Government unitedly in resolving this issue.

It appears from the deliberation of the DoP Secretary that the health ministry is already seized of the matter. The concerned departments are also apparently batting for quality, and trying to strengthen some specific capacity building areas, such as, increasing the number of inspectors and other drug control staff.

Reports also keep coming on the poor quality clinical trial data in India, including data fudging, as was recently detected by the foreign drug regulators. Intriguingly, nothing seems to be changing on the ground. In these areas too, the industry can unitedly try to protect the innocent patients from the wrongdoers, demonstrating enough credible and publicly visible real action.

From the anguish of the DoP Secretary on the critical quality related issue, it appears, there is a huge task cut out for the Indian drug regulators to ensure uniform and high drug quality standards for health and safety of all Indian patients’, just as their counterparts in America.

It is unfortunate to note from his observation that pharma industry associations are not visibly working in unison on many such issues in India.

B. The UCPMP:

The Edmund J. Safra Center for Ethics of Harvard University, while deliberating on “The Pharmaceutical Industry, Institutional Corruption, and Public Health” dwelled on the legal, financial, and organizational arrangements within which the pharmaceutical industry operates. It said, this situation sometimes creates incentives for drug firms and their employees, that conflict with the development of knowledge, drug safety, the promotion of public health, and innovation. More importantly, they also make the public depend inappropriately on pharmaceutical firms to perform certain activities and this leads to institutional corruption.

Illustrating from Professor Marc Rodwin’s project, the article said pharma players provide substantial discretionary funding for important medical activities, such as, continuing medical education, medical research, medical journals, and professional medical societies, which can encourage unwanted and undesirable compromise and bias in favor of their interests.

The same sentiment was also well-captured in an editorial of the well-reputed international medical journal BMJ of June 25, 2014. It unambiguously articulated, “Patients everywhere are harmed when money is diverted to the doctors’ pockets and away from priority services. Yet this complex challenge is one that medical professionals have failed to deal with, either by choosing to enrich themselves, turning a blind eye, or considering it too difficult.”

The editorial underscored the point that success in tackling corruption in healthcare is possible, even if it is initially limited, as anti-corruption bodies in the United Kingdom and US have shown to a great extent. With this, BMJ planned to launch a campaign against ‘Corruption in Medicine’, with a focus on India.

The DoP initiative:

Initiating a step in this direction, on December 12, 2014, the DoP announced details of the ‘Uniform Code of Pharmaceutical Marketing Practices (UCPMP)’, which became effective across the country from January 1, 2015. The communique also said that the code would be voluntarily adopted and complied with by the pharma industry in India for a period of six months from the effective date, and its compliance would be reviewed thereafter on the basis of the inputs received.

Not a panacea:

It is worth noting, since the last three and a half decades, ‘Code of Pharmaceutical Marketing Practices’, prepared by various global pharma trade associations and most of the large global pharma companies individually, have come into existence purported for strictest voluntary adherence. These are being relentlessly propagated by them and their trade associations, as panacea for all marketing malpractices in the drug industry. Squeaky clean ‘pharma marketing codes’ for voluntary practices can be seen well placed in the websites of almost all large global pharma players and their trade associations.

The concept of a pharma marketing code and its intent are both commendable. However, the key question that follows: are all those working in practice? If the answer is yes, why then mind boggling sums in billions of dollars are being paid as settlement fees by a large number of global pharma companies for alleged colossal marketing malpractices in different countries of the world?

Mandatory UCPMP:

As happens with any other voluntary pharma marketing code of a global drug company or their trade associations, however mighty they are, similar non-compliance was detected by the DoP with voluntary UCPMP.  This gross disregard on the code, apparently prompted the DoP making the UCPMP mandatory, with legal implications for non-compliance, which could possibly lead to revocation of marketing licenses. 

A move in this direction, obviously necessitated meaningful discussion of the DoP with all stakeholders, especially the pharma trade associations. According to the Secretary, the discussions got unduly protracted, crippling his decision making process to put the mandatory UCPMP in place, soon.

Divergent views of pharma associations?

Thus, it is now quite clear that one of the reasons for the delay in making the UCPMP mandatory is the divergent views of various pharma trade associations.

In the Secretary’s own words, “To take an example of uniform marketing code, we thought we could arrive at a common solution. But even after 7-8 meetings, we failed to come to a conclusion. It’s only now that we have arrived at a code.” 

However, the bottom-line is, as on date, we don’t know when would the mandatory UCPMP come into force in India.

Conclusion:

The reverberation of virtual helplessness in the recent utterances of the Secretary of the DoP, has naturally become a cause of great concern, especially for the patients. There is still no sign of early resolution of the critical issue of dubious quality, both in the drug manufacturing and clinical trials in India.

The concerned ministries would require to demonstrate unwavering will and unflagging zeal for good governance with accountability, to set things right, without any further delay. When US-FDA can, why can’t the DCGI succeed in doing so? The Government is expected to ensure that justice prevails in this area, for the patients’ sake, soon enough.

Similarly, wrong doings in pharma marketing practices also need to be addressed by the DoP, initially making the UCPMP mandatory having strong legal teeth, to start with, notwithstanding the fact that the trade associations mostly work at cross-purposes, in this area too.

As I hear from the grapevine, especially the MNC trade associations, both inside and outside the country, are trying hard to take, especially, the owners of the large Indian pharma companies on board, in several ways, basically to further their crusade on various self serving issues, such as dilution of Indian Patents Act.

That said, taking serious note of the observation of the DoP Secretary that the Indian drug control is the “weakest in the world”, together with the challenges that he is facing in containing pharma marketing malpractices, I hope, the honorable Prime Minister’s Office (PMO) may wish to intervene soon, in order to promptly contain these snowballing public health menace.

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.

Marketing Off-label Use of Drugs: A Path Much Abused?

Posted on by
Reply

As many would know, prescribing any medicine for disease conditions that are not approved by the drug approving authorities while granting its marketing approval, is generally termed as ‘off-label’ use of drugs.

It is also a usual practice in most of the regulated markets of the world that once the drug regulators give marketing approval of a medicine, which is indication-specific, physicians are free to prescribe these as they deem necessary. However, the drug manufacturers can seek prescription support from the doctors only for the indications as approved by the appropriate government authorities.

Even the USFDA had articulated, “the best way to address any concerns that the information about those (off-label) uses is not reaching medical practitioners is to get those uses in the labeling. We believe that the risks of allowing drug companies to distribute journal articles and other information about off label uses far outweigh any benefits.”        

Since long, most of the drug regulators across the world, including the Drug Controller General of India (DCGI) have prohibited the sales promotion for unapproved uses of drugs to doctors. Nevertheless, the practice continues ignoring its serious consequences.

Monitoring of ‘off-label’ use is challenging: 

Monitoring of off-label use of medicines is quite challenging too by the drug regulators, especially in India, where post marketing surveillance is generally just on paper.

In this regard, a recent research study that I shall refer to below in this article, has quite appropriately suggested, “Future electronic health records should be designed to enable post market surveillance of treatment indications and treatment outcomes to monitor the safety of on and off-label uses of drugs.”

As India intends to move towards the ‘Digital’ space, this suggestion would be quite implementable by the DCGI, as the ‘Smart Cities’ start coming up.

Some examples of extensive off-label usages: 

According to the study done by a team of experts in medical information – Iodine, using the top drugs by number of monthly prescriptions, the following is a list of 4 medications with surprising off-label uses:

Drug Approved Indication Off-label Indication
Abilify (Aripiprazole) Schizophrenia, Bipolar Disorder, Major Depressive Disorder (adjunctive), Autism-related Irritability, Agitation associated with Schizophrenia or Bipolar Mania, other Insomnia
Lyrica (Pregabalin) Management of: neuropathic pain associated with diabetic peripheral neuropathy, post herpetic neuralgia, fibromyalgia, neuropathic pain associated with spinal cord injury; adult patients with partial onset seizures (adjunctive) Anxiety
Namenda (Memantine) Moderate to severe dementia of the Alzheimer’s type ADHD, OCD
Synthroid (Levothyroxine) Low thyroid hormone levels, some types of goiters, management some types of thyroid cancers Depression

Off-label use and increasing risks of drug safety: 

In its November 02, 2015 online issue, JAMA Internal Medicine published an article titled, “Association of Off-Label Drug Use and Adverse Drug Events (ADE) in an Adult Population.” The objective of this study was to monitor and evaluate off-label use of prescription drugs and its effect on ADEs in an adult population.

This particular study assumes importance, as off-label use of prescription drugs without strong scientific evidence has been identified as an important contributor to preventable Adverse Drug Events (ADEs), especially in children. However, despite concerns in this regard, no systematic investigation on the effects of off-label drug use in adult populations is being performed, regularly.

The detail analysis of this study reveals that not only is the benefit of off-label prescription is uncertain, but the risks of ADEs could make the ‘risk-benefit ratio’ quite unfavorable. So much so that in a large number of cases, no drug treatment will be a much better option.

According to the authors, the risk for ADEs grew as the number of prescription drugs the patient used increased. For example, patients using eight or more drugs had more than a 5-fold increased risk for ADEs compared with patients who used one to two drugs.

The study involving 46,021 adult patients, receiving 151,305 prescriptions between January 2005 and December 2009 was done in Canada. Of those prescriptions, more than 10 percent were prescribed for off-label use. Interestingly, out of that group, more than 80 percent prescriptions were for off-label uses without any robust scientific evidence supporting the use.

Based on the findings the researchers concluded that off-label use of prescription drugs is associated with ADEs.

The article suggested:

  • Caution should be exercised in prescribing drugs for off-label uses that lack strong scientific evidence.
  • Future electronic health records should be designed to enable post market surveillance of treatment indications and treatment outcomes to monitor the safety of on and off-label uses of drugs.

Pharma industry strongly opposes off-label use, when it suits them:

Interestingly, pharma industry vehemently opposes off-label use of drugs, when it suits them.

To give just a couple of examples, recently a new law that permits prescribing of drugs for off-label uses in France has reportedly been strongly opposed by the pharmaceutical industry in Europe.

Pharma trade associations argue, “the above move of France is directly in opposition to European Union’s laws that prohibit member states from supporting off-label use for economic purposes, and is a trend that undermines the current regulatory framework and could put patients’ health at risk.”

Besides France, they have also submitted a complaint against Italy to the European Commission over the country’s new off-label rules.

Common methods followed for off-label marketing:

The other side of the story is that, reportedly many pharma companies continue promoting off-label uses of drugs aggressively, for significant commercial gains.

According to ‘The Centers for Medicare & Medicaid Services (CMS) – a federal agency within the United States Department of Health and Human Services, some of the off-label drug promotion methods of the pharmaceutical companies are as follows:

• Paying incentives to sales representatives based on sales for off-label use

• Paying kickbacks to physicians to prescribe drugs for off-label use

• Disseminating misleading posters promoting off-label use

• Paying physicians:

- To pretend to be the authors of articles about off-label uses when the articles were actually written by manufacturers’ agents

- To serve as members of “advisory boards” promoting off-label use

- To travel to resort locations to listen to promotions about off-label use

- To give promotional lectures in favor of off-label use to fellow practitioners

• Publicizing studies showing efficacy of off-label uses, while suppressing studies showing no efficacy.

Even the Uniform Code of Pharmaceutical Marketing Practices (UCPMP) of the Government of India does not allow such sales and marketing practices. But these all continue to happen, unabatedly.

A path much abused?

Although most of the drug companies publicly advocate self regulation to avoid unethical marketing practices, the situation on the ground is much different, across the world. 

The following are just a few examples of serious business consequences faced by some of the well-known global pharma and biotech majors, besides many others, from the United States Department of Justice, for alleged off-label promotion of drugs: 

  • On November 4, 2013, Johnson & Johnson (J&J) was asked to pay more than US$ 2.2 billion to resolve criminal and civil liability arising from allegations relating to the prescription drugs Risperdal, Invega and Natrecor, including promoting for uses not approved as safe and effective by the USFDA and payment of kickbacks to physicians and to the nation’s largest long-term care pharmacy provider.  
  • On July 30, 2013, Wyeth Pharmaceuticals Inc., a pharmaceutical company acquired by Pfizer, Inc. in 2009, agreed to pay US$490.9 million to resolve its criminal and civil liability arising from the unlawful marketing of the prescription drug Rapamune for uses not approved as safe and effective by the USFDA. 
  • On December 19, 2012, Amgen Inc. pleaded guilty and paid US$762 million to resolve criminal liability and false claims allegations.
  • On July 2, 2012 GlaxoSmithKline LLC (GSK) pleaded guilty and paid US$3 billion to resolve its criminal and civil liability arising from the company’s unlawful promotion of certain prescription drugs, its failure to report certain safety data, and its civil liability for alleged false price reporting practices. This resolution is the largest health care fraud settlement in the US history and the largest payment ever by a drug company, so far. 
  • On May 7, 2012, Abbott Laboratories Inc. pleaded guilty and agreed to pay US$1.5 billion to resolve its criminal and civil liability arising from the company’s unlawful promotion of the prescription drug Depakote for uses not approved as safe and effective by the USFDA.  This resolution is the second largest payment by a drug company and includes a criminal fine and forfeiture totaling US$700 million and civil settlements with the federal government and the states totaling US$800 million.  Abbott also was reportedly subjected to court-supervised probation and reporting obligations for Abbott’s CEO and Board of Directors.
  • On October 21, 2011, Pfizer Inc. agreed to pay US$14.5 million to resolve false claims allegations related to its marketing of the drug Detrol. 
  • On June 10, 2011, Novo Nordisk was asked to pay US$25 million to resolve allegations of off-label promotion of Novoseven.
  • On September 30, 2010, Novartis agreed to pay US$422.5 million to settle criminal and civil investigations into the marketing of the anti-seizure medicine Trileptal and five other drugs. The government accused Novartis of mislabeling, paying illegal kickbacks to health care professionals through speaker programs, advisory boards, entertainment, travel and meals. 

Hence, it appears that the path followed by many pharma players to inform the doctors about the judicious off-label use of drugs only in circumstances where approved treatments have failed, is being much abused. 

A conflict of interest? 

Many doctors believe that there is also a distinct upside for off-label use of drugs, as flexibility of a physician to prescribe drugs off-label offers important advantages too, especially in circumstances where approved treatments have failed. This is indeed true and indisputable.

However, the reality is, many pharma industry, in general, actively encourage off-label use of drugs for commercial benefits through expanded use of their respective brands.

Aggressive drug promotion for various off-label uses, reportedly being so widespread and indiscriminate, many physicians can’t even remember the approved indications of drugs. Hence, they do not necessarily go for off-label use only when approved treatments have failed.  In this context, on November 23, 2015, ‘The Wall Street Journal (WSJ)’ in an article titled, “Risk of Off-Label Uses for Prescription Drugs” reported as follows:

“A 2009 study published in the journal Pharmacoepidemiology and Drug Safety found that 1,199 physicians in a national survey were able to identify the FDA-approved indication of 22 drugs only about 55% of the time. The physicians surveyed included primary-care doctors and psychiatrists.” 

On the other hand, the patients generally expect that the prescribed drugs will be safe. They want to administer evidence based approved medicines. Some of them have even started expressing that these evidences must also be disclosed to them.

Hence, there seems to exist a clear conflict of interest in this matter between the patients, drug manufacturers and perhaps the doctors, as well.

Conclusion:

The magnitude of general off-label use of drugs is reportedly increasing and is likely to increase further, exposing patients to increased risks of ADEs.  Although the business consequences of getting engaged in this unwanted process indiscriminately could at times be quite adverse, in the balance of probability between slim chances of getting caught, and expected creamy return, many pharma players continue to feel that this risk is worth taking.

Therefore, the moot question that needs a pragmatic answer is, for patients’ safety, when the global and local pharma majors talk about prescriptions of only impeccable evidence based medicine, do they walk the talk?

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.

 

Drug Price Control in India: A Fresh Advocacy With Blunt Edges

Posted on by
Reply

It is no-brainer that the advocacy initiatives to influence the new Government doing away with the ‘Drug Price Control’ in India has re-started by flooring the gas pedal. A fresh invigorating effort, apparently a pretty expensive one, has been initiated in July 2015 with an interesting study conducted on the subject by an international market research organization, sponsored by a multi-national pharma trade association in India.

Having gone through the report, it appears to me, as if the whole purpose of the study was to rationalize an ‘advance’ conclusion in mind, weaving plethora of data around it for justification.

The report presents an abundance of selective data, apparently to rubbish the very concept of ‘Drug Price Control’ in India. In that process, it reinforced the existence of a deep seated malady in the overall sales and marketing strategic framework of most of the pharma players, rather than failure of ‘Drug Price Control’ in India, meant for the essential drugs.

In this article, I shall dwell on this issue adding my own perspective. Although my views are different, I totally respect the findings and suggestions made in this report.

Drug price control in India:

From 1970, Drug Price Control Orders (DPCO) are being issued in India under the Essential Commodities Act, without any break, so far. The key intent of the DPCO is to provide quality essential medicines at a reasonably affordable price to the consumer. The DPCO has been amended four times since then, the latest one being DPCO 2013.

Unlike the previous ones, the span of price control of DPCO 2013 is restricted to essential medicines, as featured in the National List of Essential Medicines 2011 (NLEM 2011). The methodology of price control has also now changed to ‘marked-based’ pricing from earlier ‘cost-based’ pricing.

However, for the first time in July 2013, the National Pharmaceutical Pricing Authority (NPPA) extended ‘Drug Price Control’ beyond the Schedule Drugs, when by a notification it announced price fixation of ‘anti-diabetic and cardiovascular drugs in respect of 108 non-scheduled formulation packs under Paragraph 19 of DPCO, 2013’,

Paragraph 19 of DPCO, 2013, authorizes the NPPA in extraordinary circumstances, if it considers it necessary to do so in public interest, to fix the ceiling price or retail price of any drug for such period as it deems fit.

Although the pharma industry initially had supported the switch from ‘cost based’ price control to ‘market based’ price control and only for NLEM 2011 drugs, it took a tougher stand after the above notification. Some trade association reverted to the same good old genre, yet again, trying to establish that ‘Drug Price Control’ does not help at all. The brand new market research report under discussion in this article, appears to be a step in that direction.

‘Market failure in pharma’ where competition does not work:

In its price notification dated July 10, 2014, as mentioned above, the NPPA justified its action by underscoring ‘market failure’ for those anti-diabetic and cardiovascular drugs, where competition does not work. NPPA considered ‘market failure’ as one of the ‘extraordinary circumstances’ and explained the situation as follows:

  • There exist huge inter-brand price differences in branded-generics, which is indicative of a severe market failure, as different brands of the same drug formulation, which are identical to each other in terms of active ingredient(s), strength, dosage, route of administration, quality, product characteristics, and intended use, vary disproportionately in terms of price
  • It is observed that, the different brands of the drug formulation may sometimes differ in terms of binders, fillers, dyes, preservatives, coating agents, and dissolution agents, but these differences are not significant in terms of therapeutic value.
  • In India the market failure for pharmaceuticals can be attributed to several factors, but the main reason is that the demand for medicines is largely prescription driven and the patient has very little choice in this regard.
  • Market failure alone may not constitute sufficient grounds for government intervention, but when such failure is considered in the context of the essential role of pharmaceuticals play in the area of public health, which is a social right, such intervention becomes necessary, especially when exploitative pricing makes medicines unaffordable and beyond the reach of most and also puts huge financial burden in terms of out-of-pocket expenditure on healthcare.

I discussed this subject in my bog post of April 27, 2015 titled, “Does ‘Free-Market Economy’ Work For Branded Generic Drugs In India?”

Are medicines cheapest in India, really?

It is quite often quoted that medicines are cheapest in India. In my view, it would be too simplistic, if we compare the prevailing Indian drug prices in Rupee, against prices of similar drugs in other countries, just by simple conversion of the foreign currencies, such as, US$ and Euro converted into Rupee. To make the comparison realistic and credible, Indian drug prices should be compared against the same in other countries only after applying the following two critical parameters:

  • Purchasing Power Parity and Per Capita Income
  • Quantum of per capita ‘Out of Pocket Expenditure’ on drugs

The Department of Pharmaceuticals (DoP) with the help of academia and other experts had earlier deliberated on this issue in one of its reports on patented drugs pricing. The report established that post application of the above two parameters, medicines in India are virtually as expensive as in the developed world, causing great inconvenience to majority of patients in the country.

Hence, common patients expectedly look for some kind of critical intervention by the Government, at least, on the prices of essential drugs in India.

A new study on drug price control:

Recently, I came across a ‘brand new’ research report that tries to justify the fresh stance allegedly taken by the pharma industry on the abolition of ‘Drug Price Control’ in India.

This new study of IMS Health released on July 2015, sponsored by a pharma MNC trade association in India, titled “Assessing the Impact of Price Control Measures on Access to Medicines in India”, categorically highlights ‘price control is neither an effective nor sustainable strategy for improving access to medicines for Indian patients’.

The key findings:

The following are the key findings of the report:

  • High income patient populations, rather than the low-income targets are the primary beneficiaries of the DPCO 2013.
  • The consumption of price-controlled drugs in rural areas has decreased by 7 percent over the past two years, while that of non-price controlled products has risen by 5 percent.
  • The DPCO 2013 has resulted in an increase in market concentration and a decrease in competitive intensity.
  • Price control has increased margin pressures for small and mid-sized companies, limiting both employment and investment opportunities in the sector.
  • Price controls negatively impact internal capability-building and expertise-building initiatives, discourage local talent and undermine the government’s ’Make in India’ initiative.

The suggestions made:

In my view, the report almost repeats the same old suggestions being made by the pharma industry over decades. However, while making recommendations, this new report selectively quotes, without clearly naming them, from the draft National Health Policy 2015 and ‘Jan Aushadhi’ initiative of the DoP. It also attempts to ride on the shoulder of Prime Minister Modi’s ‘Make in India’ campaign. The key recommendations of the study are, as follows:

  • Strengthen healthcare financing and extend universal health coverage across population segments with focus on providing cover for medicines
  • Invest in healthcare infrastructure and capability building
  • Promote joint and bulk procurement mechanisms, e.g. Tamil Nadu Medical Services Corporation
  • Levy a cess on the tobacco and liquor industries to fund the healthcare sector and subsidize essential medicines from taxes
  • Introduce mechanisms to ensure availability of generics at lower prices, to improve affordability for patients i.e. set up dedicated generic medicine stores.

An official of IMS Health was also quoted by the media that sounds to me almost like pontification:

“Price control has limited impact on improving patient access and, furthermore is not aligned with the requirements of a vibrant economy like India” and the “Government’s priority should be on strengthening India’s healthcare infrastructure and extending universal insurance coverage.”

The blunt edges in the report raise more questions than answers:

I wonder, whether another apparently expensive research, such as this, was at all necessary to reinvent the same old advocacy narratives on ‘Drug Price Control’ in India.

As I note, the report highlights, “The consumption of price-controlled drugs in rural areas has decreased by 7 percent over the past two years, while that of non-price controlled products has risen by 5 percent.” If this is true, one should try to fathom:

  • What does it really mean and what are its implications?
  • Can it happen, if it has happened, just because of ‘Drug Price Control’?

I am raising these two questions mainly because, price controlled drugs are prescription medicines. Thus, post DPCO 2013, when it happens to ‘prescription only medicines’, other critical questions that come at the top of mind are as follows:

  • Are the doctors now prescribing less of price controlled drugs? If so, why?
  • Price controlled drugs being essential drugs, are the doctors prescribing less of essential drugs? If so, why?
  • Do the doctors prefer prescribing expensive ‘non-schedule’ drugs to patients against their interest? if so, why?

Further, deliberately causing decline in consumption of these drugs, for margin or whatever may be the reasons, without intimating the NPPA as stipulated in the DPCO 2013, is a serious offense, attracting stringent penal action under the Essential Commodities Act.

Therefore, if the above finding of this study is correct and assuming that NPPA is not aware of such shortages or declining consumption of essential drugs in India, yet another critical question that needs to be answered:

  • By deliberately bringing down the consumption of essential medicines, are the concerned pharma players not taking the law in their own hands?

If yes, the Government would need to act forthwith. If not, the above finding of the report is just not correct.

The DoP, NPPA and other stakeholders would, therefore, need to ferret out, which one of the above two is correct.

Thus, I reckon, to wish away ‘Drug Price Control’ in India, the fresh advocacy initiative of the pharma trade association, keeping in the forefront a new study with blunt edges, raises more questions than answers. I have given just an example here, as above.

More marketing push on ‘free-pricing’ drugs is common:

It is not uncommon that the sales of ‘free-pricing’ drugs are usually more, as their margin is unlimited. Pharma players take increasing interest in those drugs and push them harder, almost totally controlling the ‘push-pull’ effect of drug marketing.

Globally, drug companies take increasing interest in such medicines. India is no exception. Here too ‘out of price control’ non-schedule drugs usually show higher growth, as the doctors are influenced to prescribe more of such drugs, though at the cost of consumer.

This practice may not be acceptable to many, but is a stark reality. This process is expected to continue, at least, till Uniform Code of Pharmaceutical Marketing Practices (UCPMP) is made mandatory with strict enforcement and strong punitive provisions for any violations.

Is the growth of price controlled drugs declining?

If the growth of price controlled medicines drastically comes down post DPCO 2013, that should get reflected on the declining overall sales and growth of those drugs. Similar pattern should also be visible in the growth of those types products marketed by most of the major pharma companies in India.

Let me now present the scenario of that space. The following analysis is based on the monthly retail audit data of AIOCD Pharmasofttech AWACS.

When I look at the growth of DPCO 2013 products based on NLEM 2011 and other price controlled drugs under ‘Para 19’ from January to July 2015 period in the following table, the scenario does not look as worrying just yet, as the above report has made it out to be.  

Product group-wise market growth (in Value):

Month (2015) DPCO products (%) DPCO  Para 19 Products (%) Non-DPCO Products (%) Total Market Growth (%)
July 5.1 11.8 14.2 12.9
June 5.6 14.6 16.2 14.8
May 5.3 7.2 12.1 11.0
April 11.1 11.9 18.4 17.2
March 1.6 15.6 21.7 20.9
February 13.9 14.4 20.0 18.9
January 6.9 NA 14.0 12.7

(Source: AIOCD Pharmasofttech AWACS )

Again, in the following table, when I look at the growth of DPCO 2013 products of some the very major pharma players in India, the conclusion still remains the same as above:

DPCO Products Growth (%) by major companies (Jan-July 2015):

Company July June May April March Feb Jan
Ranbaxy 20.5 31.9 29.5 17.3 27.6 20.7 53.7
Pfizer 13.0 17.4 5.7 16.7 25.6 21.1 18.6
Abbott 7.2 11.7 18.5 13.5 15.5 18.3 21.2
GSK -2.1 - 1.8 -1.2 12.2 12.2 NA NA

(Source: AIOCD Pharmasofttech AWACS )

The blunt edges fail to cut ice:

Quite expectedly, even a month after its release in July 2015, the blunt edges in the report seem to have cut no ice, especially at a very important place that matters most to the industry in this area. This observation gets vindicated by a credible media report.

On August 24, 2015 in an interview to a national business daily, V K Subburaj, the Secretary of the Department of Pharmaceuticals commented, “Price control on drugs a shot in the arm for health care” and “the Government cannot do away with it.”

He argued, “A large section of the population is poor. Suddenly, your system is disturbed if you have to spend more on drugs. Drugs are an important component of health care expenditure.”

Accepting the fact that in India, big and small companies investing in research would need more money, Mr. Subburaj said, “In India, we can’t afford to remove controls as the burden of disease is high.”

Conclusion:

With all due respect to all concerned, the above report appears to me palpably commercial, sans any worthy academic value or intellectual input that could trigger thinking for a change in the Government policy. The report apparently lacks in the required cutting edge to achieve the intended goal. The blunt edges are glaring, suggesting on the contrary, that the real action actually lies with the industry. Let me hasten to add, if any one has a different view on the subject, I would respect that with all humility.

The drug price control in India has been continuing since 1970, without any gap. The retail audit data clearly indicates that the growth of the Indian pharma industry did not get stunted or stifled during the period for this particular reason, as postulated in the above report of IMS Health. On the contrary, despite price control of drugs with all its ‘ill-effects’, as highlighted in the study, the growth of the Indian pharma industry in the last 4 decades has been nothing less than spectacular. This would consequently mean, increasing consumption of drugs, leading to improving access to medicines in India, including its hinterland, though may still not be good enough. I discussed this subject in my blog post of December 13, 2013, titled “Access to Medicine: Losing Track in Cacophony”.

Coincidentally, at the commencement of drug price control regime in India, almost all, if not all, the players in the ‘Top 10’ pharma league table of the country, were multi-national drug companies. Today the situation has just reversed. Out of ‘Top 10’, about 7 are home grown drug companies. Many of these companies were born post 1970. Without M&As by the pharma MNCs, this number could have been even higher today.

When it comes to profitability, it is worth mentioning, the soft-spoken and well-respected owner of the so called ‘low margin’ generic pharma company – Sun Pharma, is the second-richest person of the country. He created his initial wealth from India, despite ostensible ‘growth stunting’ price control – as elaborated in the above report.

By the way, what is the span of drug price control in India really – just around 18 percent of the total domestic pharma market now? More than 80 percent of the local drug market continue to remain in the ‘free-pricing’ and ‘high-profit’ zone. In that case, is the essence of the report not chanting… ‘yeh dil maange more’?

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.

A Patient-Centric State Initiative To Revolutionize Disease Treatment

Posted on by
Reply

In his State of the Union address, just before the recent visit to India in January 2015, President Barack Obama articulated the need to develop “Precision Medicine” in his country – a bold, giant and perhaps unprecedented State initiative to remarkably improve effectiveness of disease treatment.

To set the ball rolling, in his budget proposal for the year 2016, President Obama earmarked an amount of US$ 215 million for this purpose. This includes an allocation of US$130 million for the National Institutes of Health (NIH) to create a national research database of about a million American volunteers by studying their genetics together with other relevant factors, such as the environments they live in and the microbes that live in their bodies.

‘Precision Medicine’ initiative is similar to path breaking 13-year and US$3 billion Human Genome Project, that has formed the bedrock of modern genomics, President Obama said. He also expressed hope that the private healthcare sector too, including universities and foundations, will get involved to “lay the foundation” for this new initiative of the Government for the interest of patients.

Why is this approach so relevant in today’s healthcare?

In an article published in the ‘British Medical Journal (BMJ) in October 2012, Richard Smith - an editor of BMJ until 2004 and a Director of the United Health Group’s chronic disease initiative wrote:

“Doctors know that many of the patients they treat with drugs will not benefit. Many patients know that too.”

Dr. Smith also emphasized, for centuries medicine classified diseases by what could be seen, felt, and smelt. Thereafter, medical scientists in this area started defining diseases anatomically, physiologically, and biochemically. Even today, this is by and large the paradigm where most medicines fall.

Smith underscored, because of imprecise diagnosis the treatment also becomes haphazard. There is big variation in how individuals respond to drugs and yet that variation is not usually recorded. The regulators approve drugs based on their average performance even today.

The White House release also reiterates, most medical treatments have been designed for the “average patient.” This “one-size-fits-all-approach,” treatments can be very successful for some patients but not for others.

This calls for broadening the scope of disease treatment – from the conventional and error-prone ‘Disease Oriented’ approach, to relatively more unconventional and better targeted with greater value – ‘Patient-Centric’ ones, wherever needed.

Two current trends:

To address this key deficiency in the effective treatment of several dreaded diseases for many patients, following two are the current trends, as stated by William Pao, M.D., Ph.D., who led Roche’s Oncology Discovery & Translational Area research unit since May 2014:

  • We now know that on a molecular level every cancer is different – not only between different tumors, but even between different areas within a single tumor! This means that we need to match the right drug to the patient who we know will respond best to the drug, at the right time during the course of treatment.
  • Patients will have their tumors profiled not only for genetic drivers, but also for predictive immunotherapy markers at different time points in their course of treatment.

Personalized and Precision Medicine:

The above trends in the endeavor of making treatments more patient specific – thus more effective, have thrown open scientific discourse and intense research on ‘Personalized’ and ‘Precision’ medicines.

As Pfizer has described in its website:

Personalized Medicine is a unique approach to medical practice in which the individual aspects of a patient are directly considered to guide treatment planning, including his or her genetic make-up, key biomarkers, prior treatment history, environmental factors and behavioral preferences. This approach can be used to optimize pharmaceutical treatments and overall care.

Whereas, Precision Medicine is an approach to discovering and developing medicines and vaccines that deliver superior outcomes for patients, by integrating clinical and molecular information to understand the biological basis of disease. Precision medicine is the biopharmaceutical research and development paradigm that will help enable more patient-centered clinical practice, including treatment decision-making based on genetic information – an emerging standard now often described as “personalized medicine”.

As President Obama said while announcing the proposal on January 30, 2015, ‘Precision Medicine’ promises delivery of the right treatment at the right time, every time, to the right person.

He also said that the new effort will “bring us closer to curing diseases like cancer and diabetes…and give all of us access to the personalized information we need to keep ourselves and our families healthier.”

‘Precision Medicines’ Dominate Oncology segment: 

In the European Society for Medical Oncology (ESMO) 2014 Congress, pharma majors reported their latest advances on precision medicines in the cancer care. Bristol-Myers Squibb, Roche, AstraZeneca, GlaxoSmithKline (GSK), and Merck & Co. were among the companies presented updates of their most promising cancer drugs closer to this area.

According to a large pharma lobby group in the United States – The Pharmaceutical Research and Manufacturers of America (PhRMA):

“Recent advances in diseases such as cancer and cystic fibrosis are delivering on the promise of targeted treatments, and between 12 and 50 percent of all compounds currently being researched by the industry are potential personalized medicines. These advances hold great promise in improving patient outcomes and controlling costs by targeting the right medicines to the right patients.”

‘DCAT Connect’ Report of September 2014 also indicates significant increase in ‘Precision Medicines’ in the pipelines of the leading global pharma companies, which is a key change over the past decade.

In 2013, targeted therapies increased their share of the global oncology market, accounting for 46 percent of total sales, up from 11 percent a decade ago. According to IMS Institute for Healthcare Informatics, the global oncology drug market reached US$ 91 billion in 2013 with CAGR of 5.4 percent from 2008 to 2013.

Taking note of this trend, it appears that in the near future ‘Precision Medicines’ would possibly be the most promising class in the treatment of cancer, particularly in breast cancer, lung cancer and certain types of leukemia. This is mainly because medical scientists are already quite acquainted with the molecular signatures of different types of cancer related tumors.

Medical scientists and researchers are also working on ‘Precision Medicines’ to more effectively address many other diseases, such as, diabetes, cardiovascular and ailments related to several types of infections.

Increasing potential:

Realization of the potential of ‘Precision Medicines’ to improve care and speed the development of new treatments has just only begun to be tapped.

In recent times, scientists and researchers have accelerated efforts to understand more about biomarkers for this purpose. A study conducted by the German Association of Research-Based Pharmaceutical Companies (vfa) indicates that more than 20 percent of clinical trials carried out since 2005 focused not just on agents, but also on biomarkers. Before 1990, only one in twenty clinical trials addressed biomarkers.

According to another report, last year, 20 percent of all new drug approvals in the United States were for “Precision Medicine” treatments. This vindicates, yet again, the immense potential to turn genetic discoveries into innovative disease treatments for patients.

A bold state sponsored research initiative:

State funded, ‘Precision Medicine’ initiative is a bold new step of the American Government to revolutionize improvement in healthcare and treating disease. It is expected to pioneer a new model of patient-powered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients.

As the White House release reiterates, most medical treatments have been designed for the “average patient.” As a result of this, “one-size-fits-all-approach” treatments can be very successful for some patients but not for others. This is changing with the emergence of ‘Precision Medicine’, an innovative approach to disease prevention and treatment that takes into account individual differences in people’s genes, environments, and lifestyles.

In this process, ‘Precision Medicine’ gives clinicians tools to better understand the complex mechanisms underlying a patient’s health, disease, or condition, and to better predict which treatments will be most effective.

Opposite view:

In an op-ed titled, ‘Moonshot’ Medicine Will Let Us Down, published recently in The New York Times, the author argued with his differing viewpoints.

I am quoting below three of those arguments:

  • “For most common diseases, hundreds of genetic risk variants with small effects have been identified, and it is hard to develop a clear picture of who is really at risk for what. This was actually one of the major and unexpected findings of the Human Genome Project. In the 1990s and early 2000s, it was thought that a few genetic variants would be found to account for a lot of disease risk. But for widespread diseases like diabetes, heart disease and most cancers, no clear genetic story has emerged for a vast majority of cases.”
  • “Another unexpected finding of the Human Genome Project was the problem of ‘missing heritability.’ While the statistics suggest that there is a genetic explanation for common conditions and diseases running in families or populations, it turns out that the information on genetic variants doesn’t explain that increased risk.”
  • “The idea behind the “war on cancer” was that a deep understanding of the basic biology of cancer would let us develop targeted therapies and cure the disease. Unfortunately, although we know far more today than we did 40-plus years ago, the statistics on cancer deaths have remained incredibly stubborn.”

I am sure, you will analyze the above points with the facts that you have at your disposal on this subject to arrive at a logical conclusion.

Current Applications:

Though these are still early days, initial benefits of ‘Precision Medicines’ have been reported in many areas, such as:

  • Genetic analysis of patients dealing with blood clots: Since 2007, the U.S. Food and Drug Administration has been recommending genotyping for all patients being assessed for therapy involving Warfarin.
  • Colorectal cancer: For colon cancer patients, the biomarker that predicts how a tumor will respond to certain drugs is a protein encoded by the KRAS gene, which can now be determined through a simple test.
  • Breast cancer: Women with breast tumors can now be effectively screened to determine which receptors their tumor cells contain.
  • Cystic fibrosis: In America, patients with a rare form of cystic fibrosis now can choose a drug designed specifically to target the genetic defect causing their illness. Specialized medical centers, such as “individualized medicine centers” at the Mayo Clinic, are also available to the patients for effective treatment.

Ethical issues:

While following this pursuit of excellence of the genetic scientists in the realm of disease treatment, some experts have reportedly raised flags of caution. They strongly feel that DNA code sequencing brings to light a “very real privacy concerns” of individuals.

GeneWatch UK is an organization that investigates how genetic science and technologies will impact on our food, health, agriculture, environment and society. They have been strongly arguing, if genome sequencing is extended to entire population, individuals and their relatives could then be identified and tracked by matching their DNA with the genome stored in the respective health records. This move, as contemplated by them, could “wipe out privacy” with an impact on the society.

Thus, the ethical and social issues in the development of ‘Precision Medicine’ primarily in the area of genetic testing need to be effectively addressed, sooner.

Conclusion:

The quest for moving away from conventional and error-prone ‘Disease Oriented Treatment’ paving the way for unconventional and value added individual patient-specific ones, may soon come to fruition.

Advances in ‘Precision Medicine’ have already led to powerful new discoveries and several new treatments that are tailored to specific characteristics of individuals, such as a person’s genetic makeup, or the genetic profile of an individual’s tumor.  This is leading to a transformation in the way the world can treat diseases such as cancer.

Patients with breast, lung, and colorectal cancers, melanomas and leukemia, for instance, should be provided with facilities in specialist hospitals to undergo molecular testing as a part of patient care, enabling physicians to select treatments that improve chances of survival and reduce exposure to adverse effects.

Although, the potential for precision medicine to improve care and speed the development of new treatments has only just begun to be tapped, some skeptics do say that tailoring medical treatments to individual characteristics of each patient is both overly optimistic and cost-prohibitive.

Be that as it may, in the balance of probability the benefits of prudent use of ‘Precision Medicine’ far outweigh the concerns expressed. This evolving new paradigm would help saving not just significant expenses, but also precious time that is usually spent on ‘trial-and-error treatments’, by enabling clinicians to determine quickly which therapies are most likely to succeed.

Though lot many grounds would still need to be covered in this area, the State sponsored ‘Precision Medicine’ initiative of America to revolutionize disease treatment, in my view, is indeed a laudable one, every way.

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.

What President Obama And Prime Minister Modi Discussed On IPR And Healthcare In India

Posted on by
Reply

During the recent visit of the US President Barack Obama to India from January 25-27, 2015, both the domestic and international media was abuzz with the speculation, whether or not India would concede some ground to America on the prevailing, generally considered, well balanced patent regime in India.

Many expected that the American delegation would succeed in getting some specific assurances from Prime Minister Narendra Modi to follow the line of the US style Intellectual Property Rights (IPR) in India, which would help the American pharma companies to maximize their financial returns in the country.

The assurances from India were expected mainly in areas involving grant of patents even to those pharma products, that do not quality for the same under section 3(d) of the Indian Patents Act 2005, dilution of provisions for Compulsory License (CL) and creation of a new provision for Data Exclusivity in the country, besides a few others.

As everyone noticed, just before the US President’s visit, interested groups both in India and also from abroad intensified lobbying and released op-eds to create pressure on the Indian negotiators, in general, and the Prime Minister Modi in particular.

Terming the Indian Patents Act weak, the lobby groups turned the Indian IPR regime on its head. Playing the role of India’s benefactor, they re-packaged their shrill collective voice into pontificating words while giving interviews to the Indian media by saying: “A strong IPR regime could allow the country (India) to make a major contribution to tackling health challenges, both domestically and around the world.”

Additional US interest in Indian IP regime from TPP perspective:

Exemplary demonstration of India’s resistance to intense external pressure, time and again, for dilution of the IP regime in the country, seems to have become a model to follow for the emerging economies of the world, in general. This trend now gets reflected even among some of the members of the 12-nation Trans-Pacific Partnership (TPP), which is a proposed regional regulatory and investment treaty.

According to reports, TPP members, such as, Brunei, Malaysia, Singapore and Vietnam are negotiating hard to get incorporated somewhat similar to Indian IP rules in the TPP agreement. Besides America, other members of the TPP are Australia, Japan and New Zealand, Canada, Chile, Mexico and Peru.

TPP negotiations are generally expected to follow the overall framework of American laws. However, according to media reports, based on the leaked draft of the TPP, the data exclusivity period for biologic medicines has already been negotiated down to 7 years, from 12 years under the US Affordable Care Act.

However, on January 27, 2015, US Senator Orrin Hatch, Chairman of the Senate Finance Committee reportedly said that he would oppose Senate approval of the TPP, if it does not provide 12 years of patent protection for biologics.

The same day, at a hearing before the House Ways and Means Committee, US Trade Representative Mike Froman reportedly reiterated, “The US is insisting on 12 years of IP protections, even though the Obama administration’s budget calls for 7-year exclusivity on biologic meds.”

It is also worth noting that Nobel laureate Joseph E. Stiglitz in an op-ed titled, “Don’t Trade Away Our Health”, published in The New York Times of January 30, 2015 commented as follows:

“TPP could block cheaper generic drugs from the market. Big Pharma’s profits would rise, at the expense of the health of patients and the budgets of consumers and governments.”

Clicking on this short video clip you will be able watch another similar viewpoint on TPP, its general perspective and what it encompasses.

Thus, the closely guarded ‘turf war’ on TPP is now heating up, making negotiations increasingly tougher to arrive at a consensus on the IP rules that would be applicable to pharmaceutical products in this trade initiative. Consequently, the evolving scenario has prompted the interested groups to keenly follow, with hopes, the outcome of Presidents Obama’s recent visit to India, especially in the pharma IP areas. This is because, many emerging economies of the world are now appreciative of the prevailing well-balanced patent regime in India.

After the 12-nation TPP agreement comes into force, probably following the lines of the US IP laws, it is quite possible that India may sometime in future would prefer to be a part of this agreement for greater trade facilitation, as the country comes closer to America…Who knows?

However, in that case the bottomline is, India would have to amend relevant provisions of its Patents Act in conformance with the requirements of mainly the US pharmaceutical companies and the IP laws prevailing in America, as this will be necessary to become a new member of this treaty.

Discussion in the summit meeting:

According to the Joint Statement on the summit meeting released by the White House, President Obama and Prime Minister Modi discussed the following subjects related to IPR and Healthcare in India, as detailed below:

  • Reaffirmed the importance of providing transparent and predictable policy environments for fostering innovation.  Both countries reiterated their interest in sharing information and best practices on IPR issues, and reaffirmed their commitment to stakeholders’ consultations on policy matters concerning intellectual property protection.
  • Reaffirmed their commitment to the Global Health Security Agenda (GHSA) and announced specific actions at home and abroad to prevent the spread of infectious diseases, including a CDC-Ministry of Health Ebola and GHSA preparedness training, expansion of the India Epidemic Intelligence Service, and development of a roadmap to achieve the objectives of the GHSA within three years.
  • Committed to multi-sectoral actions countering the emergence and spread of antimicrobial resistance (AMR), and cooperation in training of health workers in preparedness for infectious disease threats. The Leaders agreed to focus science and technology partnerships on countering antibiotic resistant bacteria and promoting the availability, efficacy and quality of therapeutics.
  • Welcomed further progress in promoting bilateral cooperation on cancer research, prevention, control, and management and agreed to continue to strengthen the engagement between the CDC and India’s National Centre for Disease Control.
  • Welcomed the upcoming completion of an Environmental Health, Occupational Health and Injury Prevention and Control MoU between the U.S. Centers for Disease Control and Prevention and the Indian Council for Medical Research to further collaborative efforts to improve the health and welfare of both countries’ citizens.
  • Agreed to expand the India-U.S. Health Initiative into a Healthcare Dialogue with relevant stakeholders to further strengthen bilateral collaboration in health sectors including through capacity building initiatives and by exploring new areas, including affordable healthcare, cost saving mechanisms, distribution barriers, patent quality, health services information technology, and complementary and traditional medicine.
  • Pledged to encourage dialogue between the U.S. Department of Health and Human Services and its Indian counterparts on traditional medicine.
  • Pledged to strengthen collaboration, dialogue, and cooperation between the regulatory authorities of the two countries to ensure safety, efficacy, and quality of pharmaceuticals, including generic medicines.
  • Agreed to accelerate joint leadership of the global Call to Action to end preventable deaths among mothers and children through a third meeting of the 24 participating countries in India in June 2015.  As host, India will showcase the power of new partnerships, innovations and systems to more effectively deliver life-saving interventions.
  • Also lauded the highly successful collaboration on a locally produced vaccine against rotavirus, which will save the lives of an estimated 80,000 children each year in India alone, and pledged to strengthen the cooperation in health research and capacity building through a new phase of the India-U.S. Vaccine Action Program.

As stated earlier, during this summit meeting, US lobbyists were reportedly nurturing a hope that Prime Minister Modi would eventually agree, at least in principle, to jettison section 3(d) on the patentability criteria enshrined in the Indian Patents Act 2005 and significantly water down the country’s Compulsory License (CL) provisions. This expectation increased, when the US President made the investment promise of U$4 billion in India.

That said, from the above points of discussion in the joint statement, it appears that no breakthrough on the part of the US was achieved especially in the IPR space, during the summit.

However, in other areas of bilateral healthcare co-operation, such as, science and technology partnerships in countering antibiotic resistant bacteria; cancer research and traditional medicines; the reaffirmations made by the two leaders are encouraging.

US pressure on IP to continue:

Going by India’s reaffirmation during the summit meeting of its commitment to consultations with America on policy matters related to IPR protection and US Trade Representative Mike Froman’s reported affirmation of the following to the US lawmakers during a Congressional hearing held on January 27, 2015, it is construed by the IP activists that the kettle has possibly started boiling:

- “We have been concerned about the deterioration of the innovation environment in India, and we have engaged with the new government since they came into office in May of last year about our concerns,”

- “We held the first Trade Policy Forum in four years in November. I just returned from India yesterday as a matter of fact … and in all of these areas, we have laid out a work program with the government of India to address these and other outstanding issues.”

- “We are in the process of providing comments on that draft policy proposal on IPR, and we are committed to continuing to engage with them to underscore areas of work that needs to be done in copyright, in trade secrets as well as in the area of patents,”

- “We’ve got a good dialogue going now with the new government on this issue, and we’re committed to working to achieve concrete progress in this area,”

Media reports also indicate that US pressure on IPR would continue, as they highlight:

“Threatened by free trade of high-quality and affordable medicines, US-based pharmaceutical companies and politicians friendly with the industry are using prominently placed op-eds, large advertisements on Washington, D.C. buses, and letters to President Obama to spread false information -claiming India’s rules are not legal or discourage innovation. The companies have been threatening to withhold investment if India does not adopt weaker patent laws that would extend pharmaceutical monopolies and stymie the country’s generic industry.”

I discussed some of these issues in my blog post of January 19, 2015, titled “New National IPR Policy of India – A Pharma Perspective”.

Conclusion:

Irrespective of whatever the US-India Joint Statement says on IPR, some experts do apprehend that Indian Government may now wilt under continuous intense pressure from the American Government. This is mainly because, India’s Commerce and Industry’s Minister has reportedly sought America’s inputs in the finalization process of the new National IPR policy of the country.

On this score, let me hasten to add that it may not be prudent to read too much into it, as seeking stakeholders’ comments on such matter is a practice that India has been following since long on various issues and policies.

However, at the same time, other groups of experts nurture a quite different viewpoint. They are confident that the nationalist Modi Government, under no circumstances would concede its long nurtured strategic ground on IPR to the US power play.

Emerging countries across the globe are keenly watching this intense game of  ‘Power Chess’, as they plan to emulate India in many of the pharmaceutical IP areas to uphold the public health interest, providing affordable healthcare to all.

These are still early days. Thus, in my view, on January 25, 2015, what President Barack Obama and Prime Minister Narendra Modi discussed on the IPR regime in India may not be as important as what they would eventually decide to agree, disagree or agree to disagree in this area, moving on from here.

Only time would prove…not just who is right, that is pretty obvious to many, but who wilts at the end of the day…and more importantly, why?

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.

“Meeting Unmet Needs of Patients”: A New Direction

Posted on by
Reply

The much-hyped phrase of the global pharma majors – ‘meeting unmet needs of patients’, is very often used to create an aura around newer patented drugs of all kinds, from original to banal, including evergreen varieties such as:

Evergreen Drug/Brand Medical Condition Original Drug/Brand
Levocetirizine (Vozet) Allergies Cetirizine (Zyrtec)
Escitalopram (Lexapro) Depression Citalopram (Celexa)
Esomeprazole (Nexium) Acid reflux Omeprazole (Prilosec)
Desloratadine (Clarinex) Allergies Loratadine (Claritan)
Pregabalin (Lyrica) Seizures Gabapentin (Neurotonin)

I do not have any terrible issue with this usage, as many stakeholders, including various governments, have already started differentiating between the ‘Chalk’ and the ‘Cheese’ kinds of patented products and contemplating future course of action, accordingly. The recent development in South Africa is one such example.

That said, there is now a greater need to ponder over the much bigger picture in the same context and direction, which would improve predictability of treatment outcomes by manifold. Simultaneously, such R&D initiatives would help reducing the overall cost, especially for dreaded diseases like cancer, mainly through highly targeted drugs and consequently avoiding the risk and associated wastage, as often happens with the prevailing ‘trial and error’ therapy approach, thereby benefitting the patients immensely. This is mainly because no drug is 100 percent effective with inconsequential side-effects for all patients of any disease type.

Genetics and Genomics Science made it possible:

With already acquired knowledge in genetics, genomics and genome sequencing capability, it is now possible to precisely predict a person’s susceptibility to various disease types and proactively working out measures to help either avoiding ailments, such as, non-infectious life threatening and chronic diseases altogether, if not, making their treatment more predictable and less expensive, as stated above.

If organized efforts are made to extend the application and benefits of this science to a larger section of population, those R&D initiatives can really be construed, unquestionably, as ‘meeting unmet needs of the patients’, just as ‘first in kind’ category of innovative drugs are recognized by the scientific community and the civil society as a whole.

A treatment revolution in the offing:

Expectations are rapidly building up that evolving genetics and genomics science based technological know-how would ultimately revolutionize the practice of medicine ushering-in the pathway of personalized medicine for a large number of patients.

Definition: 

A report from the Tufts Center for the Study of Drug Development defines personalized medicine as “Tailoring of medical treatment and delivery of health care to individual characteristics of each patient, including their genetic, molecular, imaging and other personal determinants. Using this approach has the potential to speed accurate diagnosis, decrease side effects, and increase the likelihood that a medicine will work for an individual patient.”

The aim: 

The aim of personalized medicine is, therefore, to make a perfect fit between the drug and the patient. It is worth noting that genotyping is currently not a part of clinically accepted routine. However, it is expected to acquire this status in the western world, shortly.

To give a very quick example, genetic differences within individuals determine how their bodies react to drugs such as Warfarin – a blood thinner taken to prevent clotting. It is of utmost importance to get the dosing right, as more of the drug will cause bleeding and less of it will not have any therapeutic effect.

In the field of cancer, genetic tests are now being done by some oncologists to determine which patients will be benefited most; say with Herceptin, in the treatment of breast cancer.

Thus, with personalized medicine the health of a patient will be managed based on personal characteristics of the individual, including height, weight, diet, age, sex etc. instead of defined “standards of care”, based on averaging response across a patient group. Pharmacogenomics tests like, sequencing of human genome will determine a patient’s likely response to drugs.

Disease prevention: 

In addition, such medicines would help identifying individuals prone to serious ailments such as, metabolic, cardiac, endocrine, auto-immune, psychosomatic, including cancer of various types; enabling physicians to take appropriate preventive measures much before disease manifestations and in that process would help containing the overall treatment cost.

Cost of genome sequencing:

Sir John Bell, Professor of Medicine at Oxford University, reportedly said in early December 2012 that personalized medicine for all could soon be a clear possibility, as everybody will be able to have their entire DNA make-up mapped for as little as £100 (Rs.10, 000 approx.).

This estimate seems to be realistic, as the price of genome sequencing has fallen by 100,000-fold in 10 years. This cost is expected to further decline, as genome of any person essentially remains unchanged over time. Thus, this information might become a part of an individual’s medical record allowing the doctors to use it as necessary.

Summary of key advantages: 

To summarize, the expected benefits from personalized medicine, besides very early diagnosis as stated above, are the following:

1. More Accurate Dosing: Instead of dose being decided based on age and body weight of the patients, the physicians may decide and adjust the dose of the medicines based on the genetic profiling of the patients.

2. More Targeted Drugs: It will be possible for the pharmaceutical companies to develop and market drugs for patients with specific genetic profiles. In that process, a drug needs to be tested only on those who are likely to derive benefits from it. This in turn will be able to effectively tailor clinical trials, expediting the process of market launch of these drugs.

3. Improved Healthcare: personalized medicine would enable the physicians to prescribe ‘the right dose of the right medicine the first time for everyone’ without any trial or error approach, resulting in much better overall healthcare.

Current use:

Though these are still the early days, initial usage of personalized medicine is now being reported in many areas, such as:

Genetic analysis of patients dealing with blood clots: Since 2007, the U.S. Food and Drug Administration has been recommending genotyping for all patients being assessed for therapy involving Warfarin.

Colorectal cancer: For colon cancer patients, the biomarker that predicts how a tumor will respond to certain drugs is a protein encoded by the KRAS gene, which can now be determined through a simple test.

Breast cancer: Women with breast tumors can now be effectively screened to determine which receptors their tumor cells contain.

In addition, this approach would also help clinicians to determine which particular therapy is most likely to succeed on which patient.

Present outlook: 

A September 2013 article published in Forbes Magazine titled, “Personalized Medicine May Be Good For Patients But Bad For Drug Companies’ Bottom Line” says, although personalized medicine offers tremendous potential for patients, because of the dual burdens of expensive clinical trials and diminished revenue potential, the concept may become unsustainable in the long term, the attitude of regulators will be critical to drug companies’ willingness to embrace personalized medicine, and to its wider application.

In my view, for greater interest of patients to ‘meet their unmet needs’ global pharma, majors, academics, respective governments and the drug regulators should find a way out in this new direction, sooner.

Indian initiatives:

Some companies, both well known and lesser known, are making collaborative progress, keeping low profile, in the genome sequencing area in India, which will ultimately make expensive treatments, such as cancer, more predictable and simultaneously affordable to many.

The concerns:

While the progress in the field of personalized medicine is quite heartening, some experts have reportedly been sounding a note of caution. They strongly feel that DNA code sequencing brings to light a “very real privacy concerns” of individuals.

The key argument being, if genome sequencing is extended to entire population, individuals and their relatives could then be identified and tracked by matching their DNA with the genome stored in the respective health records. This move, as contemplated by the opponents, could “wipe out privacy” with a significant impact on the society.

A paper published in ‘Scientific American’ dated January 2014, titled “What Fetal Genome Screening Could Mean for Babies and Parents” deliberated that today doctors are closer than ever before to routinely glimpsing the full genetic blueprints of a fetus just months after sperm meets egg. That genomic reconstruction would reveal future disease risk and genetic traits even as early as the first trimester of pregnancy – raising another ethical issue that could hugely impact parents’ decision threshold for deciding to terminate a pregnancy or influencing how they rear their child.

Thus, all these ethical and social issues in the development and usage of personalized medicine must be appropriately addressed under a well deliberated ethical, social, legal and regulatory framework of each country.

Conclusion:

Though in Europe and to some extent in the United States, treatments based on personalized medicine have already been initiated, we are still in a nascent stage for this novel concept to get translated into reality for the benefit of a much wider population across the world.

Lot of grounds may still need to be covered, especially in the realm of medical research and also to work out the regulatory pathways for personalized medicine in healthcare by the pioneers of this great concept and more importantly by effectively addressing the ethical concerns raised on this subject.

If collaborative initiatives are taken jointly by academia, R&D based global pharma majors and medical diagnostic players towards this new direction with a clearer focus and  supported by the law makers, a huge unmet needs of patients will truly be met, giving yet again a fresh impetus to the much hyped phrase “Meeting Unmet Needs of Patients”, though in a refreshingly new direction.

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.