From the study done so far by Jananeethi in this area, we would like to make following comments for your consideration.
- Flaws in informed consent process
The existing national (ICMR) and international guidelines on clinical drug trials make it mandatory that participants could be recruited to trials only after taking their informed consent. From our experience it is found that the participants are not even informed that they are recruited into a drug trial. The details of drug trials, risks and possible side effects of the trials are not communicated to the participants. One of the strange justifications put forward by a principal investigator is that if everything is communicated to the patients as required, they (patients) won’t agree to participate in the trial. He says, due to their low level of understanding in this area they will misinterpret the information and will hesitate to participate. Being a medical doctor he should know the after effects and possible consequences of the trial. Hence he gives only censored information that will amount to professional cheat as the patients totally confides in the doctor. The patients are not given the copy of the signed informed consent form depriving them any document to prove their participation in a given trial. It is also found that the doctor is recruiting his own patients without any monitoring by an independent doctor who is supposed to check the conflict of interests involved in such cases. The doctor is exploiting the trust reposed on him by the patient.
2- Absence of insurance coverage and compensation to the participants
The existing guidelines require ensuring proper insurance coverage or adequate compensation scheme for the trial participants. The truth is that there is no insurance coverage as such for the participants; in fact insurance coverage is available to the doctor who conducts the trial in order to meet any liability that may occur due to any serious adverse event during the conduct of clinical drug trial. It was also revealed that these poor patients are denied of their trial benefits including daily wages and traveling expenses. Where those who don’t know that they are recruited into a drug trial how we can expect the enforcement of basic rights available to trial participants?
3- Denial of post trial benefits
Good clinical practices require that once the trial drug found effective the trial participants of the drug trial are entitled to get that drug either freely or at a subsidized rate. But this beneficial clause is not observed by the persons responsible for the conduct of drug trials. Hence the participants are not getting the benefits. Here we would like to highlight an instance from our own experience. During an interview with a leading oncologist in Kerala who conducts several drug trials. One question asked to him was that why he should conduct clinical drug trials. His answer to the question was that he was actually doing a service to his patients by recruiting them in to drug trials because many of the patients were from poor background and they were not in a position to buy available standard treatment for their ailment. However, he had no answer to the question whether the trial subjects were getting those drugs at concessional rate once the trial was successfully completed. Here two issues come to surface; one – once the drug gets marketing license and comes to market these poor patients are not able to buy the same because of because of its exorbitant costs. Two- during the trial period most of the trials are done on Placebo method hence seriously ill cancer patients are denied of available standard treatment. So, ultimately these patients due to their poverty are becoming guinea pigs for giant pharmaceutical companies and their vulnerability is exploited in the name of service.
4- The ‘Ethics Committees’ are unethical/dysfunctional/totally ineffective
Maintenance of ethical standards and best practices in clinical drug trials are the most sacred duty of the Ethics Committees (Institutional Review Board). But from our experience it is found that the present ethics committees are in no way useful and effective to check the unethical and corrupt practices in drug trials. The reasons are manifold- starting from the composition it fails to bring any positive result. After interviewing the Chairmen and members of ethics committees of government and private medical colleges and hospitals, it was manifestly exposed that most of the members were totally ignorant about their role and responsibilities as a member of ethics committees. Many of the private hospital managements act like co-operatives helping each other, defeating the basic purpose of ethics committees. Committee meetings take place rather irregularly, and members other than doctors from the concerned hospital are not attending these meetings, hence the ethics committee’s approval becomes a mere sham on procedures. Most of the members are in someway related to hospital managements and close associates of the principal investigator.
Out of many members interviewed, only one member got some training in this field. As per the GCP Guidelines the members should get some basic training in the good clinical practices but it is not happening and in result they are not in a position to question the unethical trials that lead to gross violations of the rights of human participants.
5- Lack of Transparency
One of the most disturbing facts in clinical drug trials was the deliberate, willful denial of any information with regard to the drug trials. The area of drug trials remains completely dark, not even the names of Ethics Committee Members are not disclosed. Not even queries under RTI were duly answered. Concerned chief investigators behave with arrogance and disrespect to norms established in a civilized society. Everything is done in a clandestine manner. Many of our requests were turned down by the authorities raising the confidentiality clause. We honestly believe that the confidentiality clause, meant to protect the best interests of human participants actually works against the interests of participants and hence needs a review. The government departments and concerned institutions are abysmally ignorant or insensitive in this regard.
6- Questionable role of the CROs
The emergence of a new entity by name the Contract Research Organization (CRO) has caused much concern and alarm in the area of medical research. CRO is only a private business enterprise, concerned of sheer profits. With their entry in the fray, the pharmaceutical companies have gone behind the curtain. Now, the research institution does not come in the picture. Drug trial takes place based on a secret understanding between the agents of the CRO and the concerned chief investigator. Seldom only is the hospital management informed of such a trial on patients in the hospital. We also have information that the trials are being conducted in fairly large laboratories and post graduate departments of few colleges. Doctors practice drug trials in their private clinics too. Hospital managements and medical practitioners are offered huge incentives and remunerations for obliging for such trials. It means clinical drug trials with the advent of CROs have become merely a commercial enterprise, at the cost of the life mostly poor and illiterate and marginalized people. This amounts to sheer violation of international covenants and mandatory norms and guidelines. For these reasons, we honestly feel that the CROs should be banned forthwith. Let every drug trial be based on a MoU signed by the research institution and the concerned pharmaceutical firm, the terms and conditions should be clearly spelled, transparent and the stake holders are held liable to any possible adverse effects on the participant.
7- Placebo method
As per the existing national and international guidelines placebo based trial can be carried only when there is no available standard treatment for the disease. But the fact is that most of the drug trials are done on placebo that results in the denial of available treatment.
In the light of above mentioned observations we would like to make following suggestions-
- We need a specific legislation with stringent provisions to punish violators and to safe guard the rights of trial participants. From our experience so far and discussions with members of ethics committees and doctors who are actually conducting clinical drug trials make it obvious that at present protection of the rights of participants solely depends on the personal integrity and honesty of the doctor and his team who conduct drug trials. State governments are ignorant about huge number of drug trials that are being conducted in the state. So it is of paramount importance to have a state level mechanism apart from the DCGI and ICMR in order to have strong monitoring on drug trials that are being carried out in respective states.
- The composition, selection and function of ethics committee need a through revamping in order to make this body more effective. They should monitor the trial and must be allowed to meet trial participants on a random basis to ensure whether there is any serious adverse event reported or not. This will help to check the genuineness of the informed consent and to eliminate the chances of corruption in the process of recruitment. It must be ensured that members of the committee are independent and got sufficient training on GCP. The details of ethics committee members (name, address and contact numbers etc.) must be publicly exhibited in the hospitals, conducting clinical drug trials and the same has to be given to each trial participant. The decision of the ethics committee whether approved or disapproved must be published along with the reasons for the same and the same has to be shared among different ethics committees. It is also ideal to have a central authority to monitor the functioning of ethics committees. The name and contact details of ethics committees must also be given in CTRI Registry.
- Every participant must given an identity card apart from the signed copy of the informed consent form with necessary details regarding drug trials. This will serve as a strong evidence of participation and will be useful for claiming insurance / compensation for any adverse effects and also to ensure the availability of post trial benefits to trial participants.
- Insurance coverage to trial participants must be ensured before they are recruited in to a drug trial.
- Review the confidentiality clause; it is high time to review the confidentiality clause that goes against the interests of trial participants. In the name of protecting the commercial and trade interests of the company the confidentiality clause makes everything related to drug trials secretive. So, in our view except in case of disease like HIV and similar diseases which may invoke social stigmatization on patients the details of drug trials and patients must be made public.
- The details of drug trials including the patient’s details must be retained for a minimum period of five years. Because in many cases the principal investigator leaves the hospital after or in the middle the trial and the side effects of the trial may occur after the trial period. It is also necessary that the drug trial must be done by the doctor with the full knowledge of the hospital management so that even if the doctor leaves the hospital the management could be held responsible for the reparation of participant’s rights. Because during our study it was found that the doctor conducted a drug trail even without the knowledge of hospital management and once it was exposed there was no record available in the hospital.
- It is also necessary to have a contract or a memorandum of understanding between all the parties involved in the drug trial process i.e. between the pharmaceutical company, CRO if they are involved, the principal investigator and the hospital management. This will help to ensure better transparency and accountability in the conduct of clinical drug trials.
- The use of placebo must be avoided except where there is no alternative treatment available for the disease in question.