How Can We Build a Clinical Research Infrastructure in India for India?

We must resolve to fund at least a few large clinical studies every year that address critical healthcare issues in the country, and the solutions for which can also only ever emerge from within the country.

Outside the Tata Memorial Cancer Hospital in Mumbai. Credit: Wikimapia

Outside the Tata Memorial Cancer Hospital in Mumbai. Credit: Wikimapia

The last century has seen tremendous improvements in human health. From the eradication of smallpox to the improvements in maternal and neonatal health, there is much to be happy about. This has translated to an improvement in average life expectancy; in India for example, the life expectancy in 1915 was 24 years and recent estimates put it at 66 years and these gains are largely driven by the major advances in clinical research.

India today represents a sixth of the global population and therefore a substantial proportion of the global health problems. Many of these are challenges faced elsewhere in the world but there are also issues that are unique to India and the solutions to these problems can come from India alone. Take for instance cervical cancer. In 2012 alone, 266,000 women worldwide died from cervical cancer. The overwhelming majority (close to 90%) of these women were from less developed nations.

Cervical cancer is now increasingly uncommon in high income countries, largely attributed to the introduction of universal screening programs based on cytology-based (‘pap smear’) techniques. Unfortunately such screening programs have been deemed impractical and not cost-effective in most of the low and middle income countries – including in India. There is an urgent need for affordable and practical screening programs in countries like India. A challenge such as this will not be addressed by the rest of the world; its solution must come from within and would require sustained clinical research efforts. Efforts to develop a low cost screening technique have been in development for many years. A promising approach was using visual inspection of the cervix with acetic acid (VIA) as a screening tool. Previous studies (conducted in India and elsewhere) have looked at using trained nurses and healthcare providers to implement this test. While effective, a national screening program using this technique would be near impossible, given the lack of adequately trained healthcare providers necessary for such a program.

A group of oncologists at Tata Memorial Centre in Mumbai recently presented the results of their landmark research study that could potentially address this issue. Dr. Surendra Shastri and colleagues initiated this clinical trial in 1998; they selected women with up to 10th grade education and provided training as primary health workers – an intensive four week for performing the visual inspection with acetic acid tests followed by an annual one-week refresher course. They conducted a cluster-randomised trial, wherein 20 geographically distinct clusters in Mumbai belonging to lower socioeconomic groups were selected by simple random sampling from 70 clusters. From them, 151,538 women aged 35-64 years were numbered and randomly assigned to screening or control groups. One group (of 75,360 women) received four rounds of cancer education and VIA screening in 24-month intervals while the other group (of 76,180 women) received cancer education at enrolment and standard medical care and follow-up.

Fifteen years after the study was initiated, Dr. Shastri presented the results of this research effort at a plenary session of the annual meeting of American Society of Clinical Oncology. They showed convincingly that this screening approach could reduce cervical cancer mortality by half. Consider the herculean efforts involved with this study: the wide array of healthcare professionals and others involved in the study, the long years and substantial funding required for conducting the trial. But here at last is a low-cost, feasible and effective screening strategy that could potentially prevent 22,000 deaths related to cervical cancer in India annually.

This study by Shastri and colleagues exemplifies the type of high quality research that India can and must conduct. This was a trial that addressed an important healthcare issue that is relevant to low resource settings and evaluated an intervention that was effective and feasible.

Developing the necessary infrastructure for clinical research

A key first step in building a clinical research infrastructure would include the identification and training of motivated medical personnel with interest and aptitude in clinical research. Currently, there are 21,738 postgraduate medical training positions in India, all required to submit a research thesis prior to graduation. That is an impressive number of research studies to be completed and which, in principle, should be a cause for celebration. Unfortunately, in practice, only a few (if any) address questions of clinical relevance and only a handful are published in peer-reviewed medical journals. This is at the heart of the crisis facing the clinical research infrastructure in India.

We have a system that values quantity over the quality of research studies. There is little reason to mandate doctoral theses from individuals who are training to be future medical specialists. This is not a requirement for postgraduate trainees in countries that have a productive research output like the US. There are likely a proportion of trainees with a true interest and aptitude for clinical research; we need to identify these individuals early on and provide adequate training and resources for a successful research career. We may not have 20,000 research studies every year but the ones we do have will likely be clinically relevant.  

We also need to identify the clinical research issues that need to be tackled; despite our many advances, medicine still has innumerable unanswered questions. It is of course not practical or feasible for us to tackle all of them in India. We have the necessary expertise and mechanisms in India to identify the important clinical questions that need to be addressed. A quick review of the list of active cancer clinical trials registered in the Clinical Trial Registry of the Indian Council of Medical Research (ICMR) reveals that the majority of active trials are industry-sponsored studies of drugs or devices. No doubt these are important studies addressing important questions but the relatively small number of those with public or institutional funding speaks of an inherent malaise in the system. The guiding principles must be to address problems that are unique or critical to India (or low-resource settings in general), identifying potential interventions that might be feasible and providing adequate resources to complete the research efforts. We must resolve to fund at least a few large clinical studies (like the one from Tata Medical Centre discussed earlier) every year that address critical healthcare issues in India. This is really the only way to make meaningful advances in the health of our people.

Yet another issue is the regulatory challenges to conducting clinical trials in India. The ethics of clinical trials and possible exploitation of clinical trial participants has been in the news recently (criticism of the cervical cancer screening trial described above: here and here; our perspective on such studies; and concern and criticism on the conduct of clinical trials in India: here and here). The Supreme Court and the Government of India have both appropriately taken notice of these issues and instituted measures to address them.

However, has the pendulum has swung too far? The new regulations are onerous, bordering on draconian. We must protect the interests of clinical-trial participants without paralysing the clinical research infrastructure in the country. Take for instance the HIV/AIDS program in Haiti and South Africa or the malaria clinical trials in sub-Saharan Africa. These are just a few examples of outstanding clinical research programs that are conducting ethical high-quality research in resource constrained settings and addressing important health-care challenges. We must encourage and provide funding for multi-institutional academic cooperative groups that have institutional mechanisms in place to conduct clinical trials that are relevant and ethical in a relatively short period of time. This model has worked very well (examples here and here) in other parts of the world including several European nations and the United States.

A final challenge is to provide adequate funding for clinical research studies. Clinical research is undoubtedly expensive and resource-intensive, but with some effort it is possible to fund the next generation of high-quality studies. The funding can come from government agencies like the ICMR, non-profit organisations as well as philanthropic support. The recently established Wellcome Trust-Department of Biotechnology (DBT) India Alliance clinical and public health research fellowship is a good example for identifying and funding promising clinical research efforts in India. It is critical for us to continue providing consistent and incremental funding for clinical research efforts (as it is for funding all research activities in the country).

The last two decades have seen sustained development in India in almost all areas, including in healthcare. India now has the capacity to leverage our economic growth to build a world class clinical research infrastructure in the country. These efforts must be driven by various stakeholders: the political leadership, our bureaucracy, physician leaders and practicing doctors must all contribute to this effort. As a final note: the clinical research efforts can be only as useful as our commitment to implement the results. It is important that the results from the studies like the cervical cancer screening trial must be implemented through a national screening program. Only then can we translate the academic achievements to meaningful healthcare outcomes. Together we can establish a clinical research infrastructure in India that can tackle some of the most important health challenges of our time.

Sham Mailankody is a hematologist and medical oncologist, cancer researcher and assistant attending physician at the Memorial Sloan Kettering Cancer Center in New York.