Dr Pramesh, you have been an investigator on clinical trials in India for 11 years. What keeps you motivated?
| Dr C S Pramesh |
Clinicians who stick on at academic institutions like Tata Memorial Centre, or KEM or CMC Vellore choose to stay on because we want to do more than just patient care.
I can speak for cancer but I am sure it’s true for most other diseases as well that the kind of cure rates we are able to offer patients, as a result of clinical research, are far better (than in normal practice). And I guess that is what motivates us: trying to find something better for our patients.
Especially in diseases like cancer, there is always scope for improvement. And numerous clinical trials have given us better treatment options than we’ve ever had before. Having said that, in clinical research there is always the possibility of the experimental treatment being only as good as the current treatment (that’s the reason it’s called research!) but the only way we can look for something better is to try it in a trial. So we won’t know unless we test the new treatment in a rigorously conducted clinical trial.
In fact cancer is one area where personalised treatment really works because we have to try to fit the treatment to the patient rather than giving a standardised drug to all patients.
What are the vulnerabilities that you face as an investigator and how do you handle them; both your own as well as that of patients?
There is always the possibility that a drug might not work and that is something that both the investigator and patient have in mind. So what we typically do is see what other preliminary research has been done on this treatment; has it shown some success in preclinical animal studies, does it have a sound biological rationale, has it shown some promise in earlier phase human studies, etc. So you are looking for some kind of signal that it might actually work. So if you see some kind of signal of such success, then we are more comfortable trying it out in a larger trial.
Secondly, what happens in a trial is that there are so many safety mechanisms built into the process that we would not miss out on a drug that is not working for too long. Nor would we miss out on important side effects for too long. And typically in a cancer trial, new treatment is usually tried as an add-on to the current treatment or in a situation where the patient has already exhausted all available options.
What changes would you like to see?
There are a few things that I would like to see changed. One, I’d like biomedical researchers to introspect – I think the medical profession needs to change a lot as far as research goes. Some doctors get into clinical research for the wrong reasons. They are not adequately trained for clinical research. Unfortunately, even today there is no formal training in medical research at either the under graduate (UG) or post graduate (PG) level. This is a shame because a lot of them do end up doing research and they are not very well trained to do it. Training in research methodology should be a mandatory part of UG and PG training.
Another thing that I think needs to change is the level of public awareness about medical research. And by public, I don’t just mean patients on clinical trials but the general public.
The most aggravating thing about this situation is that in the developed countries like the US and the UK, medical research is being driven by the lay public. They are demanding that their governments spend more on medical research. In fact, the “war against cancer” in the US came into being because of public pressure on the Federal government to increase funding for cancer research. In many cases, public charity groups are actually funding trials. That is the way it should be.
On the other hand, here in India, you have the press as well as the general public up in arms. So forget about being a positive push, these activities are becoming a deterrent to medical research. I strongly feel that the general public has to be more proactive when it comes to clinical trials. We all want better medical treatment for ourselves. How can better treatment be ever discovered if we don’t participate in medical research? I feel it is a moral imperative for all of us to participate in medical research. Every pill that we pop today for a headache, for high blood pressure, for cancer, is available to us only because someone, somewhere has participated in a clinical trial to prove that the pill works.
How are we justified in expecting better treatment if we don’t participate in research ourselves?
Lay public in India are guided by what the media portrays and unfortunately the negative publicity in the recent past leads them to equate medical research with experimenting on guinea pigs. This is unfair because you have bad apples in all professions. Just like you have bad engineers, bad lawyers and bad accountants, you have bad medical researchers. Unfortunately the problem created by the small proportion of bad researchers is amplified and projected onto the whole profession.
This is not fair because there are so many checks and balances that for instance, in most academic institutions, a maverick researcher going wayward would be found out in just a few days. The data and safety monitoring committees and ethics committees are so stringent that they would be picked out in days. So it’s very unusual that bad research and a bad researcher go unnoticed for too long. The public needs to get this message. It is actually in the interest of pharmaceutical companies (the sponsors) and lead investigators to choose good researchers on their trials because all you need is just one bad researcher to spoil the reputation of the trial. Pharma companies and CROs are always extra careful when they are selecting sites because it is in their own interest to select good researchers.
How has your role as an investigator helped you over the years?
One major thought is that you are actually contributing to medical research and this is very gratifying. Especially in a disease like cancer where disease outcomes are not very encouraging, even a small improvement in clinical outcomes is very welcome. For example, lets take advanced lung cancer. 1995 was the first time we got proof that chemotherapy gave better outcomes in advanced lung cancer over the standard of care. If you did not give chemotherapy, the average lifespan was six months but with it, it was eight months. Even though the improvement in clinical outcomes was only two months, it was then considered an important improvement in survival rates. Today, there are some targeted treatments for advanced lung cancer which can improve survival to 24 months. Two years may not seem a big deal but for a cancer patient and his family, it is an improvement in survival by 400 per cent when you consider the baseline survival of six months. So that’s how much medical treatment has progressed thanks to cutting edge clinical research.
If we had stopped trials of that ‘experimental’ treatment in 1995, we would still have a survival of just six months. This is just one example – there are numerous others in practically all branches of medicine.
How do you counsel a patient that he needs to be on a clinical trial?
We do not try excessively hard to convince a patient to join a trial. We have three types of patients.
One group, the most problematic one, is the one who says, “Doctor, we authorise you to do whatever you feel is best for me … we trust you” without understanding anything of the trial. The second type is at the other extreme end; patients who understand everything about the trial and then make and then take a decision whether to participate or not in the trial. The third group of patients are those in the middle, who seem to understand the study when you are explaining it to them and may sign up to the study but may not actually understand all the details of the study. This could be a dangerous situation.
The first group should never be part of a trial because they do not understand anything of it. It would not be a truly informed consent. So I would be extremely wary about taking them on a trial. The second category I respect completely because theirs is an informed decision, whether to participate or not. With the third group, it usually comes down to a judgement call by the investigator who needs to take a call. We need to understand that it is practically impossible for a patient to understand every single minute detail of a trial. What is important is that he/she understands the basic information that this is part of research and not routine medical care, the types of treatment involved, the possible side effects, the possible benefits and risks of participating. I would not be comfortable trying too hard to convince a patient to join a trial when the patient is ambivalent.