Need to take a pragmatic view of clinical trials

“I believe we need to address the issue of clinical trials not with blind emotion but with a rational understanding of the benefits and with greater compassion for those suffering for want of effective medicine.” Kiran Mazumdar Shaw CMD, Biocon

The drugs we use to treat any condition – from an innocuous cough to a life-threatening cancer – are the outcome of painstaking human clinical trials. These trials are the only way to credibly determine the safety and efficacy of drugs. Without trials there is no way pharmaceutical research can advance to improve disease management and the very quality of life.

Drugs go through several stages of development prior to human trials. The trials themselves are approved and regulated by government agencies and undertaken only after animal experiments prove their safety beyond any evidentiary doubt. Even then, the safety and efficacy of a drug on humans needs to be proven before it can go to market. Unpredictable outcomes are but natural in this process – no wonder then that they are known as ‘trials’! The successful outcomes are of vital significance – for they not only help the patients involved in the trial but also transform the lives of hundreds of thousands who benefit from the commercial launch of such experimental drugs. Take some recent life-changing cancer drugs which have helped overcome what was thought to be an incurable condition – two such that readily come to mind are Herceptin for the treatment of breast cancer and Gleevec for the treatment of leukaemia.

Freezing effect

The recent controversy over human clinical trials in India is worrisome as it has had a chilling effect on the clinical trial approvals in the country. Only six studies have been cleared by DCGI in 2013 so far, last year over 260 studies were approved. A series of articles in newspapers apparently aimed at tarnishing the entire clinical trials sector and some NGOs going to court with public interest litigations seem to be fuelling it. These individuals and entities are whipping up emotions by portraying only the darker side – showing how some terminally ill patients didn’t survive in a clinical trial. As the Indian Society for Clinical Research (ISCR) has said, those participating in trials are already afflicted. Their death, therefore, was not due to the drug. If they were terminally ill, the drug perhaps was not as effective as was anticipated.

It is important to note that many trials in India are phase III trials which are global trials with a stringent common protocol for already well-tested drugs. Hence, the risks to patients are minimal. In any case, without a trial it is impossible to determine if and how a drug works. Factors such as racial characteristics, genetic make-up, and individual biochemistry also have a bearing on the outcome of a trial. Using Herceptin as a case in point, without a clinical trial it would have been impossible to learn that the drug is only useful for patients who have tumours that are HER2 positive.

In this entire discourse, what is really frightening is that we are succumbing to a herd mentality. Instead of addressing specific issues that need fixing in some clinical trials, the effort seems to be to paint all clinical trials with the same brush.

The result is that the government is now penalising everybody for the non-compliance of a few instead of weeding out the bad elements.

The Government’s move is destroying the innovation culture in India and hindering access to affordable treatment options for patients in India. Such knee-jerk reactions will only make much-needed new drugs inaccessible to more Indians. Beyond the horror fiction, let us examine the reality of clinical trials in India.

Trials in India

All drugs need to be tested on ethnic populations to ensure their efficacy; so Indian patients must have representation in trials. Genetic variations can result in different levels of drug efficacy and hence the need for local clinical trials. For example, the cancer drug Iressa worked well in Japanese populations but not so in Caucasians which led to the identification of a gene mutation that determined response. Moreover, some diseases are more prevalent in India. These range from malaria and chikunguniya to tuberculosis, kala azar and head and neck cancer. Drugs for such diseases can be best tested in India.

For innovative drugs like Itolizumab, which Biocon has developed for the treatment of psoriasis, or the oral insulin drug that is under development, clinical trials in India are very critical to bring novel treatments for patients in India. If we do not have a conducive environment for clinical trials in India, companies like Biocon and others will be forced to conduct these studies in other parts of the world, which will be a huge setback not just to the Indian patients but also to Indian companies engaged in innovation.

The answer, therefore, is not in shackling clinical trials – it will only result in denying better and cheaper drugs to millions of Indian patients.

We must remember that trials are conducted with the highest degree of transparency and with the complete consent of patients and families, disclosing not just potential benefits but also risks involved. As in any industry, there may be some black sheep – and they must be dealt with utmost severity. But that does not mean that the entire industry is suspect. Industry is conducting ethical clinical research, and the term ‘guinea pigs’ being used for participating patients is a serious insult.

India advantage blunted

India was well placed to be the largest clinical research hub of Asia but due to shackling of clinical trials the CRO sector, is under huge pressure.

The genetic diversity of the Indian population makes India an attractive destination for companies to carry out tests. But currently just about two per cent of global trials take place in India. China, a relatively late starter, has over nine per cent share of the global clinical trials. Clearly, India is losing out this battle as well.

Pragmatic view paramount

The fact is that our current legal framework is strong enough to ensure transparency and ethical practices during the conduct of clinical trials. However, India has not been able to capitalise on its potential in clinical trials owing chiefly to a lack of effective implementation of regulation.

Additionally, the ill-informed and unfounded media reports are hindering the clinical progress in India. One writer in a recent newspaper article suggested that poor patients should be given a higher compensation. Does the writer realise that this is tantamount to inducement? All human life is equally precious, so how does one price it? Instead of dismissing clinical trials, we need to adopt a rational perspective of clinical trials – understand how they are run, realise their criticality to patients, and address issues objectively.

Putting clinical trial approvals on hold is not the solution, instead the government needs to efficiently monitor ongoing trials for regulatory compliance and penalise non-compliant companies, investigators and CROs. Existing laws need to be implemented stringently to ensure that trials are conducted ethically with utmost diligence and transparency. Compensation in case of adverse events should not just be fair but also equitable without discriminating between patients. A better way of compensation would be to provide patients who participated in a successful trial with free or subsidised drug.

If we curtail clinical trials and global pharma companies move to China, South Korea and other East and South Asian countries – as they are doing – we will only end up hurting Indian patients. We believe we need to address the issue of clinical trials not with blind emotion but with a rational understanding of the benefits and with greater compassion for those suffering for want of effective medicine.