Abstract
Drugs and vaccines have played a crucial role in increasing dramatically the average life span of humans all over the world since the beginning of the last century. However, there are problems—often, though not always—created by vested interests or by ignorance of their use. They range from the sale of sub-standard or obsolete formulations to unethical nexus between pharmaceutical companies at one level and commercial health care establishments on the other. This article lists some of these problems which get magnified in the prevailing circumstance of a burgeoning profit-driven private health sector and inadequate and ineffective regulatory framework.
Drugs
The problems with regard to the use of allopathic drugs in India range from quality, regulation, irrational use because of the nexus between pharmaceutical companies and the largely commercial health care establishments, etc. Fake or sub-standard Hazards, JNNURM, infrastructure, slums, resettlement, water, contaminated allopathic drugs may represent as much as 25 per cent of our drugs (IMPACT, 2006), though there are no reliable estimates.
When a few years ago members of the staff of the Sambhavna Trust, set up in Bhopal to take care of the Bhopal gas tragedy victims, raided the dispensaries of Government hospitals whose primary objective was to take care of the gas tragedy victims, and sent randomly selected drugs for analysis, it was found that most of them were fake or sub-standard (IANS, 2006). This was reported extensively but no action was taken against the manufacturers—many of them located in Indore. Then there is also the question of expired drugs being sold to unsuspecting and ignorant customers. The tragedy is that even when it is established that the drugs are fake or sub-standard, or drugs that were sold had crossed the expiry date, no action is generally taken against the culprit.
Till recently, the drug costs in India were the lowest anywhere in the world. This was largely because, till 2005, we had no product patent and our outstanding chemists devised better and cheaper processes than the patented ones for making the drug (Greene, 2007). Now that we permit product patent under pressure from the US and major multinational drug producers in the West, the situation is poised to change dramatically to the detriment of the interests of a vast proportion of our countrymen, unless we have the courage to make use of certain enabling provisions of the Trade Related Aspects of Intellectual Property Rights (TRIPS) agreement, such as its articles 7, 8, 27.2 1 and the one concerning compulsory licensing. 2
Fortunately, the 2005 Act amending our patent rules does not allow patenting of minor chemical modifications or analogues of existing patented drugs. It also does not allow the patenting of microorganisms and other living entities, including genes. But our courts do not always do what is obviously the right thing to do. Therefore, we need to watch carefully what the courts decide in the case of Novartis (a major foreign drug producer) whose application for a patent had been disallowed on account of the above provision in the 2005 patent amendment Act. In my view, there is really no legal case at all in favour of Novartis.
There is an unfortunate but very widely prevalent and effective nexus between drug companies on the one hand and commercial health care establishments and doctors (with a few but notable exceptions) on the other. This nexus involves not only direct payments by drug companies to doctors but also indirect support to them through expensive gifts or financing of travel to meetings in India or abroad (Times of India, 2012a; Down to Earth, 2012). This, leads to a vast proportion of our doctors, particularly those who work in corporate hospitals and other commercial health care establishments, to prescribe expensive and/or branded drugs when cheaper generic drugs would have been just as good from the point of view of the patient. In fact, many medical shops attached to commercial health care establishments do not keep generic drugs. Then, there is often no bulk purchase by government hospitals which would ensure reduction in cost.
Our doctors are generally far too busy making as much money as they can. More often than not, they do not ask the patient if he/she is taking any other drug so that they can ensure that there is no interaction between a drug that the patient is already taking and the newly prescribed drug. In fact, most doctors are unaware of drug–drug interaction which is not emphasised in the course leading to a medical degree.
Often the instructions given to the patients by the doctors in regard to the use of the prescribed drug are insufficient or not clear to the patient, with the result that compliance is poor. One result of poor compliance has been the development of antibiotic resistance which, as it turns out, is now very common in the country. We, thus, have a fair number of cases of infection by Methicillin-resistant Staphylococcus aureus (MRSA), a strain of Staph aureus that is resistant to all antibiotics excepting vancomycin which can be used only under careful medical care. In fact, we now have an emergence of MRSA which is also resistant to vancomycin; if you are infected with this organism, the chances that you will survive are extremely slim. In the US alone, there may be 15,000 to 20,000 deaths per year in recent years on account of hospital-acquired infection by such multi-drug resistant organisms.3, 4
Given the realities, it is not only important to have the right drug but also to make sure that it has been stored properly at the prescribed temperature. Some drugs require storage at, say, 4°C which is generally the temperature in a refrigerator. In many places, there are long power cuts when the temperature of the refrigerator in a drug store would go up substantially. Few drug stores in the country, if any, have a back-up generator. Not only that a large number of medical shops in the country function as general merchants and have no trained pharmacists as required by law. There is no system to review medical stores in the country.
The government hospitals are supposed to provide free drugs to patients. However, often there is no stock of the required drug, or the quality of the drug supplied is poor. This is a consequence of the public sector health care becoming poorer day by day in every respect.
Often, the major drug companies advertise that a particular drug which has been approved for a particular use is also useful for other ailments without the drug having been properly tested for such ailments. There is, thus, misleading marketing of drugs, and bribing of doctors to prescribe such drugs for conditions for which they have not been approved. This, in medical terminology, is called ‘off-label use’ (An example in our country has been that of Latrazole). Such unfair practices led to a fine of US$13 billion imposed on leading American pharma companies (Times of India, 2012b). However, the fact is that such a fine would make little difference to the pharma company. Thus, Pfizer was fined US$2.3 billion in 2009 which was very small compared to its revenue of US$67.4 billion during the same year.
We also have Drug Controller General of India (DCGI) approving drugs for sale in India which have either not been approved in the country of origin or their trials have been inadequate. Even in the case of appropriately approved clinical trials, the manner in which the trials are conducted leaves much to be desired, not only from the legal but also the ethical point of view. For example, the consent forms are not adequate or appropriate, and serious adverse events (SAEs) are not reported.
Very often, prescription of a drug by a doctor depends on the results of a diagnostic test. We have a system of accreditation of diagnostic laboratories under the National Accreditation Board for Laboratories (NABL) which was set up nearly 10 years ago at the initiative of an organisation in Hyderabad called The Medically Aware and Responsible Citizens of Hyderabad (The MARCH). However, there are less than 200 laboratories accredited under this system whereas Hyderabad alone may have a couple of thousand diagnostic laboratories. We have strong reasons to believe that the results of many of these laboratories are totally unreliable. This can be easily tested by giving the same sample to a number of laboratories at the same time. If the diagnostic tests are not reliable, the diagnosis could be incorrect and the patient could be prescribed a wrong drug.
There is another source of wrong drugs being prescribed. When you go to a clinical (diagnostic) laboratory for the prescribed tests, your values are given on the left while on the right are given the reference ranges for the parameter tested. As it turns out, there is a great deal of evidence that the reference ranges or standards we are using are derived from the West and may not be applicable to Indians. In fact, on account of the tremendous human biodiversity in India, we may not have just one set of reference standards for all Indians. Fortunately, at the initiative of The MARCH, the Indian Council of Medical Research (ICMR) has set up a high-power committee to work out Indian reference standards. 5
It is often said that drug prices are high because the cost of putting a new drug in the market today may be anywhere between US$1 and US$1.5 billion. Not only that, the number of new drugs (new chemical entities) coming in the market is decreasing rapidly as years pass by, so that last year, probably, not more than 15 new drugs were put in the market. The solution is to screen the repertoire of traditional plant-based drug formulations of which we have over 40,000; using 8,000 to 10,000 plants (Bhargava & Chakrabarti, 2003). Even if 4,000 of them were found to be valid using the stringent modern system of validation, in the next 100 years, India would become a world leader in health care.
The argument that the cost of a new drug is high because of the expenditure on research and development is not valid for India as drug companies spending say, ₹100 on R&D, get a tax rebate of at least ₹150!
If India wants to provide cheaper and reliable drugs to our people, we must not allow foreign companies to take over our companies in the pharma sector. Not only that we should not forget that a substantial part of the vibrancy in our pharma sector has been on account of the now defunct Indian Drugs and Pharmaceuticals Ltd (IDPL). The lesson is that we must revive public sector investment in the drug sector.
Vaccines
While India has successfully employed vaccines to eradicate diseases such as smallpox, there are serious issues with vaccine trials, especially in the context of no system of independent monitoring of quality and relevance to the population. We have tried vaccines in the country which we should have never done. For example, the Indian component of the International Aids Vaccine Initiative (IAVI) AIDS ICMR and a private company, Targeted Genetics, conducted AIDS vaccine trials in India bringing to the fore several ethical and regulatory issues and the fact that the safety of trial participants was not ensured. We try out and use unnecessary and unproven vaccines—and that too, on poor unsuspecting persons without proper informed consent. We also do not recognise that any immunisation schedule for children would need to be culture- and country-specific.
We succumb to sacrificing our interests to satisfy foreign interests. We thus decided to close our vaccine manufacturing facilities in the public sector instead of improving them so that we can import foreign vaccines (fortunately, this decision was, I believe, reversed).
Shantha Biotech had to overcome a plethora of obstacles to manufacture and market its Hepatitis, B Vaccine which is genetically engineered and which brought its price down 50-fold. In fact, a majority of funding for the above vaccine—the first genetically engineered product in India—came from Oman and not from India.
We make a wrong choice of vaccines when better alternatives are available. An example would be our choosing Sabin’s Oral Polio Vaccine (OPV) to be given in more than a dozen doses as against the Salk’s new Injectable Polio Vaccine (IPV) which gives 100 per cent immunity with two injections. This was in spite of the fact that initially we had decided in favour of the Salk vaccine and even set up a company (Indian Vaccine Corporation Limited (IVCOL)), in Gurgaon where the National Brain Research Centre is located today. This company had an outlay of ₹90 crores with Institut Merieux (one of the world’s premier and ethical vaccine manufacturers), putting in ₹50 crores and the DBT and IPCL putting in ₹20 crores each. This company was wound up subsequently, apparently after spending a substantial amount of money. This happened because in spite of the well-documented fact that OPV had problems in developing countries such as India, WHO had decided that the developing countries like India should shift to OPV. The reasons were clear. The developed countries had decided to shift to IPV from OPV. Therefore, a market had to be found for the manufacturers of OPV in the Western world. The consequence was that several Secretaries and Joint Secretaries of the Department of Health of the Government of India, Directors of Medical and Health Services of the Government of India, and at least one Director-General of ICMR were given cushy jobs with WHO (Bhargava, 1999, 2008).