Tag Archives: Patients

To prevent ‘counterfeit medicines’ from reaching the patients is the nation’s public health responsibility: Are we still in a denial mode to even accept the existence of this public health menace?

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In November 7, 2009, Financial Express reported with a headline,”Generic drug companies see a bitter pill in counterfeit“, because some believe that it has an in-built intellectual property right connotation.
The dictionary definition:

The word ‘counterfeit’ may be defined as follows:

1. To make a copy of, usually with the intent to defraud

2. To carry on a deception; dissemble

4. To make fraudulent copies of something valuable

5. A fraudulent imitation.

What does Indian Drugs and Cosmetics Act say?

May be for this reason the Drugs and cosmetics Act of India has specified that manufacturing or selling of the following types of drugs are punishable offence:

Section 17: Misbranded drugs

Section 17-A: Adulterated drugs

Section 17-B: Spurious drugs

No one has asked, so far, that as misbranding could involve trademark and design, why should it fall under Drugs and Cosmetics Act?

This was done in the past by the law makers because they believed that any attempt to deliberately and fraudulently pass off any drug as something, which it really is not, could create a serious public health issue, leading to even death.

Be that as it may, the pharmaceutical industry all over the world sincerely believes that counterfeit drugs involve heinous crime against humanity.

Definition of counterfeit drugs should cover the all types of medicines, which are not genuine:

Definition of counterfeit drugs should, therefore, cover the entire gamut of medicines, which are not genuine. Such medicines could be a fraudulent version of patented, generic or even traditional medicines and have nothing to do with patents or patent infringements.

At the same time it sounds very reasonable that a medicine that is authorized for marketing by the regulatory authority of one country but not by another country, should not be regarded as counterfeit on this particular ground in the other country, if it is not made available fraudulently.

The recent survey on ‘spurious’ and ‘sub-standard’ drugs by the Government of India:

To assess the magnitude of the menace of counterfeit drugs, Financial Express dated November 12, 2009 reported that much hyped “world’s largest study on counterfeit drugs” conducted by the Ministry of Health of the Government of India with the help of the Drug Controller General of India’s office, has come to the following two key conclusions:

1. Only 0.0046% of the drugs in the market were spurious

2. Quantum of sub-standard drugs in India is just 0.001%

From this report, it appears that India, at this stage, has nothing to worry about this public health hazard!!!
It is indeed quite baffling to understand, why did the government keep ‘misbranded drugs’, as specified in the Drugs and Cosmetics Act of India, outside the purview of this study.

Be that as it may, it appears that this survey has raised more questions than what it had attempted to answer. Such questions are expected to be raised not only by the pharmaceutical industry of India, its stakeholders and the civil society at large, but by the global experts, as well.

The problem of counterfeit is more prevalent in countries where regulatory enforcement is weak:

The menace of counterfeit medicines is not restricted to the developing countries like, India. It is seen in the developed countries, as well, but at a much smaller scale. Thus it is generally believed that the issue of counterfeit drugs is more common in those countries, where the regulatory enforcement mechanism is weak.

A study done by IMPACT in 2006 indicates that in countries like, the USA, EU, Japan, Australia, Canada and New Zealand, the problem is less than 1%. On the other hand, in the developing nations like parts of Asia, Latin America and Africa more than 30% of the medicines are counterfeits.

The role of ‘The World health Organization (WHO):

To effectively root out this global menace, the leadership role of the WHO is extremely important. Across the world, patients’ need protection from the growing menace of counterfeit medicines. As a premier organization to address the needs of the global public health issues and especially for the developing world, the WHO needs to play a key and much more proactive role in this matter.

Conclusion:

All stakeholders of the pharmaceutical industry must be made aware more effectively, without further delay, of the health threats posed by counterfeit medicines. Authorities and organizations like the Drug Controller General of India (DCGI) and its regulatory and enforcement agencies, healthcare professionals, patients, all pharmaceutical manufacturers, drug distributors, wholesalers and retailers should collaborate to play a very active and meaningful role in curbing the counterfeit drugs from reaching the innocent patients.

By Tapan 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

Ensuring ‘health outcomes’ based drugs prescriptions will be more beneficial for the patients in India than just ‘price control’ of drugs

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Currently the global pharmaceutical market is undergoing a metamorphosis. The concept of ‘evidence-based medicine’ is gaining ground in the developed markets of the world, making the pharmaceutical companies generate requisite ‘health outcomes’ data using similar or equivalent products. Cost of incremental value that a product will deliver is of key significance. Some independent organizations like, the National Institute for Health and Clinical Excellence (NICE)in the UK have taken a leading role in this matter.Global pharmaceutical companies using more ‘health outcomes’ data to set pricing strategies:In early 2009, reported agreements between Sanofi-Aventis, Procter & Gamble and Health Alliance as well as Merck and Cigna vindicate this point. These agreements signify a major shift in the global pharmaceutical industry’s approach to gathering and using ‘health outcomes’ data

In the Sanofi-Aventis/Procter & Gamble-Health Alliance agreement, the concerned companies agreed to reimburse health insurance companies expenses incurred for patients suffering from non-spinal bone fracture while undergoing treatment with their drug Actonel.

In the Merck/Cigna agreement, Cigna will have the flexibility to price two diabetes drugs based on ‘health outcomes’ data.

‘Outcomes-based’ pricing strategies are expected to become the order of the day, in not too distant future, all over the world.

The ground realities in India:

Medicines constitute a significant cost component of modern healthcare systems, across the world. In India, overall healthcare system is fundamentally different from many other countries, even China. In most of those countries around 80% of expenses towards healthcare including medicines are reimbursed either by the Governments or through health insurance or similar mechanisms. However, in India situation is just the reverse, about 80% of overall healthcare costs including medicines are private or out of pocket expenses incurred by the individuals/families.

Since 1970, the Government of India (GoI) has been adopting various regulatory measures like cost based price control and price monitoring to make medicines affordable to the common man. For those products, which are patented in India, it has now been reported that GoI is mulling the approach of price negotiation with the respective companies.

However, we should keep in mind that making drugs just affordable in India, where about 65% of population does not have access to modern medicines, is indeed not a core determinant of either healthcare value or proven health outcomes or both.

Cost-effective ‘health outcomes’ based doctors’ prescriptions are more important:

Spending on medicines can be considered as an investment made by the patients to improve their health. To maximize benefits from such spending will require avoidance of products, which will not be effective and the use of lowest cost option with comparable ‘health outcomes’.

For this reason many countries have started engaging the regulatory authorities to come out with head to head clinical comparison of similar or equivalent drugs keeping ultimate ‘health outcomes’ of patients in mind. A day may come in India when the regulatory authorities will also concentrate on ‘outcomes-based’ pricing. However, in Indian context these appear to be very early days.

Till then…

1. Get Standard Treatment Guidelines (STG) prepared for the diseases more prevalent in India, based on, among other data, ‘health outcomes’ studies.

2. Put the STG in place for all government establishments and private hospitals to start with.

3. Gradually extend STG in private medical practices.

4. Make implementation of STG a regulatory requirement.

Thus we need to discuss first what these STGs are.

Standard Treatment Guidelines (STG):

STG is usually defined as a systematically developed statement designed to assist practitioners and patients in making decisions about appropriate cost-effective treatment for specific disease areas.

For each disease area, the treatment should include “the name, dosage form, strength, average dose (paediatric and adult), number of doses per day, and number of days of treatment.” STG also includes specific referral criteria from a lower to a higher level of the diagnostic and treatment requirements.

For a developing country like India formulation of STGs will ensure cost-effective healthcare benefits to a vast majority of population.

In India STGs have already been developed for some diseases by the experts in those areas. These are based on review of current published scientific evidence towards acceptable way forward in diagnosis, management and prevention of various disease conditions

STGs, therefore will provide:

- Standardized guidance to practitioners.
- Cost-effective ‘health outcomes’ based services.

GoI should encourage the medical professionals/institutions to lay more emphasis and refer to such ‘heath-outcomes’ based evidences while prescribing medicines. This will ensure more cost effective ‘health outcomes’ for their patients.

Conclusions:

Such an approach for drug usage will help both the doctors and the patients, significantly, to contain the cost of treatment in general and the cost of medicines in particular. Encouraging and implementing ‘health outcomes’ based medicines prescription in India will require, above all, a change in the mindset of all concerned. The use of an expensive drug with no significant improvement in ‘health outcomes’ should be avoided by the prescribers, initially through self regulation and if required through an appropriate regulation.

By Tapan 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.

Fixed Dose Combination’ drugs market in India is growing faster – are there enough regulatory checks and balances to prevent market entry of ‘irrational combinations’ to ensure patients’ safety?

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The WHO Model of FDCs:The 2005 ʹProcedure to update and disseminate the WHO Model List of Essential Medicines, Criteria for Selection‘ includes the following statement regarding fixed dose combination products (FDCs):ʺMost essential medicines should be formulated as single compounds. Fixed‐dose combination products are selected only when the combination has a proven advantage over single compounds administered separately in therapeutic effect, safety, and adherence or in delaying the development of drug resistance in malaria, tuberculosis and HIV/ AIDS.ʺ

FDCs need to demonstrate clinical efficacy and safety beyond that for the individual drugs given alone. They would also need to ‘demonstrate bioequivalence of the single combined dose unit with the components administered in the same doses separately but concomitantly’.

‘Adherence’ aspect of WHO Model for FDCs is also important. Problems with ‘adherence’ could lead to inadequate and inconsistent dosing, which in turn could lead to development of drug resistance. FDCs, therefore, are expected to improve compliance reducing the risk of development of drug resistance.

However, one of the major disadvantages with the FDCs is lack of flexibility in adjusting dose of individual ingredients, even if it is required for some patients. Internationally, most popular example is the FDCs of antiretroviral drugs for HIV infected patients like, Combivir, Trzivir, Kaletra etc. Besides, there are FDCs for various other disease areas, like, infections, respiratory and cardiovascular disorders etc.

New FDCs are patent protected in the USA:

In the western world, like the USA, new FDCs may also get patent protection. A company may obtain marketing exclusivity for a new FDC even when individual active ingredients go off patent. However, in India FDCs cannot be patented as per Patent Acts of India 2005.

Market attractiveness for FDCs in India:

In India the market for FDCs is very large and growing much faster, in sharp contrast to the western world. Because of growing market demand, pharmaceutical companies in India tend to market FDCs of all different permutations and combination, at times even crossing the line of a ‘sound medical rationale’. For this reason, we find in the website of ‘Central Drugs Standard Control Organization’ (CDSCO), the banned list of so many FDCs.

Lack of regulatory compliance has created a messy situation with FDCs in India:

Introduction of new FDCs does not only warrant a ‘sound medical rationale’ but also ‘strict conformance to all prescribed regulatory requirements’ for the sake of patents’ safety.

To check unfettered market introduction of potentially harmful FDCs, the Ministry of Health issued a Notification in September 1988, including FDCs in Rule 122 E of the Drugs & Cosmetics Rules (D&CR) 1945. In effect, it removed the powers of the State FDAs to give manufacturing or marketing approval of FDCs. After the notification was issued, all manufacturers/marketers of all FDCs are required to apply only to the Drug Controller General of India (DCGI) under Rule 122E of the D&CR 1945 as a new drug, along with the stipulated fees by way of a Treasury Challan.

Since this entire process entails relatively more regulatory data generation, besides the time and expenses involved, the above Rule was continuously and deliberately broken and manufacturing and marketing approvals were routinely sought and obtained from the State FDAs. Many believe that the State FDAs were equally responsible for knowingly flaunting the Law, as were the pharmaceutical companies.

Patients’ safety – the key concern:

This complicity resulted in the market being flooded with ‘irrational combinations’ which posed a real threat to patients’ safety. The state FDAs were reminded of the Notification by the earlier DCGI. 294 FDCs got caught in this dispute. The important issue of patients’ safety in that process got converted into a legal issue, as many FDC manufacturers chose to go to the court of law to redress their grievances in this matter.

Untangling the messy knot:

As the issue got trapped into various prolonged litigations, the current DCGI took initiative of resolving this contentious issue with the help of an expert committee, involving the manufacturers.

This subcommittee cleared 48 FDCs under ‘similar FDCs already approved’, after discussing the merits and demerits, including pharmacodynamics, pharmacokinetics, side effects, dosage, medical rationale etc. of each ingredient and the combinations. The decision of the Sub Committee was then submitted to the Drug Technical Advisory Board (DTAB).

After formal approval of DTAB, a notification is expected to be issued subsequent to which each of these combinations will be construed to be a new drug and any company wishing to market/manufacture the formulation will require submitting its Application in Form 44 to the DCGI to get approval in Form 45. The process will be completed after the balance 142 FDCs, which need further examination, are individually approved.

This issue sends a clear signal to all concerned that resorting to any form of shortcuts to bypass strict adherence to prescribed regulatory requirements, could seriously jeopardise the patients’ safety. The number of FDCs banned by CDSCO and also ban of those FDCs agreed and accepted by the industry without any challenge during the above process, will vindicate this point.

Solving the current logjam is not enough:

Solving the current logjam on FDCs by the DCGI is a onetime exercise and will perhaps clear a serious mess-up created over a long period of time. It can definitely not be an ongoing process. Neither will it be desirable. There is an absolute and urgent need to follow the WHO Model for FDCs, in India, as indicated above, through appropriate regulatory processes. At the same time, the DCGI should ensure strict compliance of the Notification issued by Ministry of Health on FDCs, in September 1988. Otherwise, unchecked entry of FDCs of all possible permutations and combinations could pose a serious threat to patients’ interest and safety.

Meeting unmet needs of the patients with high quality drugs of scientifically proven high efficacy and safety profile should always define the purpose of existence of the pharmaceutical industry. Any patients’ safety related issue deserves no scope for any compromise.

By Tapan 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.

From ‘Blockbuster Drugs’ to ‘Personalized Medicines’ – will it revolutionize the way the patients will be treated tomorrow?

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Financial Times quoted Jeff Kendler, the CEO of Pfizersaying, “the era of dependence on a single or a couple of blockbuster drugs should be over. Lipitor sells U.S$ 12 billion a year. You can’t build a company predicted on the belief that you are going to find such a drug.”The argument is robust, what then are the alternatives?Rapid strides in pharmacogenomic bring in a promise of radically different way of treating diseases, as major pharmaceutical companies of the world make progress in developing much more effective medicines designed to target smaller populations. These medicines are termed as ‘personalized medicines’ and are expected to be an effective alternative to now quite unwieldy ‘blockbuster drugs’ business model.

In what way ‘Personalized Medicines’ will be different?

With ‘Personalized Medicines’ 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. Pharmacogenomic tests like, sequencing of human genome will determine a patient’s likely response to such drugs.

These are expected to offer more targeted and effective treatment with safer drugs, and presumably at a lesser cost. Such medicines will also help identify individuals prone to serious ailments like, diabetes, cardiovascular diseases and cancer and help physicians to take appropriate preventive measures, simultaneously. ‘Personalized medicines’ in that process will focus on what makes each patient so unique, instead of going by the generalities of a disease.

To give a 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.

‘Personalized medicines’, therefore, have the potential to bring in a revolutionary change the way patients are offered treatment by the medical profession. Genomic research will enable physicians to use a patient’s genetic code to arrive at how each patient will respond to different types of treatments.

In the field of cancer, genetic tests are currently being done by many oncologists to determine which patients will be benefitted most, say by Herceptin, in the treatment of breast cancer.

What is then the aim of ‘Personalized Medicines’?

The aim of ‘personalized medicines’ is 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, by 2010.

Expected benefits from ‘Personalized Medicines’:

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 Health care: ‘Personalized Medicines’ will enable the physicians to prescribe ‘the right dose of the right medicine the first time for everyone’. This would give rise to much better overall healthcare.

Role of Pharmaceutical and Biotech companies:

Many research based pharmaceutical and biotechnology companies have taken a leading role towards development of ‘personalized medicines’ in line with their key role as healthcare enterprises. India is also taking keen interest in this science.

Some important issues:

However, there are some ethical and social issues in the development of ‘personalized medicines’ primarily in the area of genetic testing and consideration of race in the development of such medicines, which need to be effectively addressed, sooner.

Can it replace the‘Blockbuster Drugs’ business model?

Realization of deficiencies in the economics of ‘block buster drugs’ R&D business model, has made ‘personalized medicines’ a reality today.

Improved efficacy and safety of treatment with ‘personalized medicines’ will prove to be cost-effective in healthcare systems. Smaller and exclusive markets for ‘personalized medicines’ are expected to be profitable for the pharmaceutical companies. But such smaller segmentation of the market may not leave enough space for the conventional ‘blockbuster model’, which is the prime mover of the global pharmaceutical industry, today.

Reports indicate that some renowned global pharmaceutical companies like, Roche, AstraZeneca, GlaxoSmithKline are making good progress towards this direction through collaborative initiatives.

Approximate cost of ‘Genome Sequencing’:

When human genome was first sequenced, the reported cost was staggering U.S$ 3 billion. However, with the advancement of technology, it came down to U.S$ 1 million, last year. Currently, the cost has further come down to U.S$ 60,000. With the rapid stride made in the field of biotechnology, combined with the economies of scale, cost of such genetic tests is expected to be around U.S$ 1,000 in near future, making it possible for people to obtain the blue print of their genetic code.

Savings on cost of Clinical trials with ‘Personalized Medicines’:

Genome sequencing will help identifying a patient population, which will be far more likely to respond positively to the new treatment. In that process, if it reduces costs of clinical trial by even 5%, expected net savings for the industry towards clinical trial have been reported to be around U.S$ 5 billion.

With ‘personalized medicines’ the innovator companies will be able to significantly reduce both time, costs and the risks involved in obtaining regulatory approvals and penetrating new markets with simultaneous development of necessary diagnostic tests. Such tests will be able to identify patients group who will not only be most likely to be benefitted from such medicines, but also will be least likely to suffer from adverse drug reactions.

Therefore, considerable cost advantages coupled with much lesser risks of failure and significant reduction in the lead time for clinical trials are expected to make ‘personalized medicines’ much more cost effective, compared to conventional ‘blockbuster drugs’.

Innovative and cost effective way to market ‘Personalized Medicines’:

With ‘personalized medicines’ the ball game of marketing pharmaceuticals is expected to undergo a paradigm shift. Roche’s model of combining necessary diagnostic tests with new drugs will play a very important role in the new paradigm.

Roche is ensuring that with accompanying required diagnostic tests, the new oncology products developed at Genentech can be precisely matched to patients.

Can ‘Personalized Medicines’ be used in ‘Primary Care’ also?

To use ‘personalized medicines’ in a ‘primary care’ situation, currently there is no successful model. However, it has been reported that in states like, Wisconsin in the U.S, initiative to integrate genomic medicines with ‘primary care’ has already been undertaken. Scaling-up operations of such pilot projects will give a big boost to revolutionize the use of ‘personalized medicines’ for precision and targeted treatment of the ailing population.

In my view, there does not seem to be any possibility of looking back now. The robust business model of ‘personalized medicines’, is now the way forward, as much for the industry as for the patients. It is a win-win game.

By Tapan 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.