Clinical research within developing countries

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Published: 20 Dec 2011
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Prof Sudeep Gupta - Tata Memorial Hospital, Mumbai, India

Prof Sudeep Gupta outlines the challenges of carrying out clinical trials in developing countries. A key problem is obtaining informed consent. Consent documentation can be very complicated and often do not consider the variations in levels of patient literacy. Although it is important that these documents contain all relevant information, researchers should be working to develop simpler documentation and to take extra time to talk forms through with patients.

Prof Gupta explains some other differences faced in studies within developing counties. These include the late stage at which patients first visit their doctor, unusual disease subtypes, a greater range of infections and the patient’s ability to pay for treatment. Work is being done to make treatments more affordable to patients in these areas but it is essential that governments and pharmaceutical companies to come together to address this issue.

2011 SABCS, San Antonio Breast Cancer Symposium, 6-10 December, San Antonio, USA

Clinical research within developing countries

Professor Sudeep Gupta - Tata Memorial Hospital, Mumbai, India

I presented a developing country perspective on clinical trials, especially pertaining to breast cancer clinical trials, and very specifically the challenges about conducting clinical trials in developing countries such as India. The most important challenge is the challenge of obtaining adequately informed consent from patients. We know that the informed consent documentation has become very detailed over the years. There is a rate of illiteracy that is substantial in many developing countries such as India, so it becomes a challenge to adequately convey the information that is contained in the informed consent documentation to subjects who participate in clinical trials. Plus there is also a language barrier. So many of these informed consent documents need translation into local languages, and while these translations can be literal, they often do not convey the essence of the study in a very appropriate manner to ordinary subjects in the developing countries.

Aside from informed consenting, there are several other challenges. The standards of care are different in developing countries, so for example, as it pertains to breast cancer, surgical standards, radiation standards, systemic therapy standards could be different. The kinds of tumours that we see, the kinds of patients that we see, are a little different. Patients present at a more advanced stage. The sub-types of breast cancer are different; it could be more of triple negative breast cancers. The patients’ ability to pay for their treatment is different, so the compensation guidelines, the reimbursement guidelines need to be different in developing countries. So those are some of the challenges of conducting clinical trials in developing countries.

What can be done to improve consent forms?

As far as I am concerned, I am a little uncomfortable with the kind of detail that is required, but I understand that that is required for regulatory purposes as well. I think what could be done is to, aside from serving them the informed consent document as it is prepared mostly in the western context, one could also serve them with a document that explains the study in a more digestible manner to the ordinary individuals in the developing countries. Plus, I think communication is the key. I have often found in my own practice and in my own experience that illiteracy is not so much of a barrier, so long as one is prepared to explain the nuances of the study to subjects and their families in adequate detail. It is just a question of time and taking the time out and taking the effort to actually convey the meaning of the study. It can be done, it just takes a little more effort.

The west is mostly interested as they look at developing countries, the sponsors of most of these trials have some drugs that they want to test. And the problem with conducting trials in developing countries is that most of the times these drugs, because of their cost, because of other financial implications, may not immediately be applicable to the developing countries. So one criticism of this sort of an activity is that the population of developing countries is being used to answer questions that are relevant to the west but not to the developing countries. But I think more is being done to improve the access of these populations to the drugs that are being researched in those countries; and many companies, many pharmaceutical companies and the non-governmental organisations have come forward with innovative schemes by which these drugs could be made available in the populations that they are researched in.

So the drug prices are exorbitant by developing country standards. And so which is why for example for a drug like Herceptin, in our own study less than 5% of patients who are HER-2 positive actually have access to that drug. But that’s not because the drug price is more than what it is in the west, it is just a question of the fact that the overwhelming majority of our patients do not have access to health insurance. So I don’t think there is predatory pricing, I don’t think there is exorbitant pricing, it’s just that the per capita income of most developing countries means that a large fraction of their populations will not have access to these drugs.

Should the onus be on pharmas to charge less in these situations?

So that’s a complex question, I don’t have a straightforward answer to that question. There can be many perspectives on that. So one perspective is that if a drug or if a device is being researched in a population, it is ethically, it will be kind of obligatory on the pharmaceutical company to make that device or that drug available at affordable prices in the developing country. But I also recognise the fact that these days drug development can be a very expensive venture, and you know you have a number of failed trials, pre-clinical, clinical, all phases of trial, and so therefore I understand that there is an economic logic to the pricing. So I don’t have a straightforward answer to your question. I think governments and pharmaceutical companies should come together to address that issue. I think there are several schemes, there are several programmes that the government of India, including both the federal governments and the state governments have started in order to increase the access of our patients to many of these drugs. Not necessarily the most expensive targeted drugs, but at least the basic chemotherapy drugs are increasingly available to the large majority of patients.

The conclusions of my talk were as follows. One is that there are several challenges in the conduct of trials and the implementation of trials, and I also mentioned some other challenges, such as the possibility of different kinds of infection in developing countries. So I suppose in San Antonio you’ve not had a case of malaria for many years, or maybe one case in the last four years. It’s a regular occurrence in Bombay where I sit. Infections can be unusual, infections can be more frequent and we know that infections are a very important adverse effect that needs to be captured. So the design of a trial has to be appropriate to the context in which it is going to be implemented. Dr Gradishar presented a clinical trial on sorafenib in metastatic breast cancer at San Antonio Breast Cancer Symposium in, I think, 2009. And there were a lot of adverse effects that had malaria, tuberculosis, other airborne illnesses and other kinds of tropical illnesses. So I think the design of the trials had to be contextual to the implementation challenges that are likely to be faced.

So my conclusions essentially were the fact that there are a number of challenges but that there are also a number of opportunities for breast cancer research in developing countries. I summarised the increasing incidence of breast cancer, especially in the urban populations of developing countries. I also emphasised the fact that case-fatality ratio of breast cancer is higher in developing countries. Even though the incidence is lower, the fraction of patients who die of breast cancer is higher and which points to deficiencies in the delivery of breast cancer care. I also emphasised the need for the delivery of evidence-based and multidisciplinary care for breast cancer in developing countries. And then I emphasised a few opportunities for breast cancer research including the large number of patients, the well-trained research staff in many emerging economies such as India, China, Brazil. And the fact that a number of clinical trials have been successfully conducted, and an increasing number of trials such as the ones that you see being presented at this symposium are being conducted globally, including in many developing countries.

In what ways do you work with other organisations?

There are several models for collaboration in Tata Memorial Hospital. One is that we undertake our own intra-mural projects. So the funding for those projects essentially comes from within Tata Memorial Hospital. There are projects that go on with extra-mural funding, and these are essentially investigatory initiated projects. And that funding could be, for example, obtained from Federal Indian organisations such as the Indian Council for Medical Research and other organisations, or from international organisations. We have sister institution agreements and other MOUs with a number of international organisations, research organisations. We also do a number of industry sponsored trials. So we have a number of collaborations, both national and international collaborations and research.

One challenge that I also mentioned only in passing was the challenge of trans-national transfer of biospecimens. And there are a number of restrictive guidelines on how you can transfer biological material between countries. So there is only a fraction of samples that you can export, and this sort of regulation is in place in many developing countries; I know for sure that it is there in India. So that is another challenge that needs to be surmounted, especially in this area of biomarker driven research.