Why does one become an investigator for a trial, either self initiated or sponsored? An unanswered question, an inclination to conduct research, urge to gather firsthand knowledge of a new molecule, social status in the medical fraternity and also some financial gain in sponsored trials.
Earlier it was easy to recruit patients from amongst the rows in the outpatient department. The patient would be indebted to the investigator for including him in the trial. Trial related adverse reactions would be generally treated as part of the trial and none or minimal compensation paid.
The major issues were operational in nature; the performance of the research assistant, correction of errors, liaising with the sponsor and ethics committee, recruitment issues etc.
There has been an upheaval in the process of conducting clinical research over the past 4-5 years. The process is now better regulated and streamlined with stringent rules made mandatory. The atmosphere is now more patient friendly with an emphasis on his/her safety and rights. Rules have been laid down for the informed consent process, compensation for trial related injury or death, accreditation of Ethics committees and sites. These changes are affecting relationships between all stakeholders in a trial.
Something similar has been happening the worldover. Ciuman RR has the following to say about the investigator sponsor relationship in EU; “The increasing formal, legal and financial framework in the last decades directly resembled and had immediate impact on the complexity of the investigator-sponsor relationship and clinical trials conduct( 1).
What is the position of the investigator in India after all these positive changes for the patient? What are his pain areas? Let us list a few.
Informed consent process: The so called informed consent process in earlier days was simple. Often the investigator would request his patient to participate and the patient would oblige. The more conscientious of the investigators did try to explain things to the patient but it was still cursory. The new recommended process mandates that adequate time is spent in explaining the pros and cons to the patient including his rights, risks, risk mitigations and available compensation. The task can be delegated but the investigator has a vicarious responsibility. There is also the Damocles sword in the form of the law that any violation of the informed consent process will be dealt with as a serious lapse on the part of the Investigators, for which the Investigator can be debarred from clinical trials
Audio visual (AV) recording of the informed consent procedure: The earlier guidance was for AV recording of the whole informed consent process for every patient. The new guideline says AV recording is a must in case of vulnerable subjects in clinical trials of new molecules(2). Who is a vulnerable subject? What about vulnerable subjects in case of old already approved molecules? Due to lack of clarity on these issues, wise and cautious investigators tend to continue the earlier process although it is time consuming.
Accreditation of self: Accreditation of the investigator himself has been made mandatory. Draft guidelines are in circulation. These make an investigator’s job difficult as it involves lot of ongoing training, paperwork, SOP generation and document management. He has little time for these activities and will have to employ additional staff.
Accreditation of site: Along with accreditation of self, the site also has to be accredited. The first few investigators at a site will have the additional burden of assisting in this activity. This will force the institutions to have a separate site management group(3).
Not more than 3 studies: As per the Ranjit Roychoudhary expert panel report, the number of clinical trials that can be undertaken by an investigator have been limited to just 3. This had been accepted through an office order in July 2014 by the Drugs Controller General of India. How does an investigator decide which studies to accept? What happens if a study has been finalised through an investigator contract and then fails to start? What if a study which started recruiting patients remains incomplete? In such cases an investigator may lose out on studies regarding subjects that are close to his/her heart. Having more than 3 studies would disqualify him during accreditation. Clarifications are awaited, but till then decision making is like waking on a sword’s edge(4,5).
Reporting ADR causality, compensation: As per Appendix XII of Schedule Y, the Investigator shall report all serious and unexpected adverse events to the CDSCO, the Sponsor or his representative whosoever had obtained permission from the CDSCO for conduct of the clinical trial and the Ethics Committee, within twenty four hours of their occurrence(6). The rule book says that if there is a delay in reporting the investigator has to provide an explanation
The decision whether the adverse event is eligible for compensation will be taken by the Ethics committee but the investigator’s opinion is also sought. Since he is the primary physician it is a big responsibility.
In conclusion the investigator is now straitjacketed in a web of rules and regulations he must follow if he has to get the satisfaction of addressing a research question that has been bothering him or a subject close to his heart
1 Ciuman RR. Sponsor-investigator-relationship: challenges, recent regulatory developments and future legislative trends Health (2011) 3:772-781
2 Ministry of Health and family Welfare. GSR 611(E) July 31, 2015
3 NABH-Accreditation Standards for Ethics Committee, Investigator, Clinical Trial Site .1st ed, Nov 2014
4 DCG(I),Office Order. Limiting number of clinical trials an investigator can undertake. July 3, 2014
5 Report of the Ranjit Roy Chaudhury expert committee, july2013
6 GSR 53(E) Drugs and Cosmetics Rules, First amendment 2013, Jan 30,2013
|Dr Vishwas Sovani, Sep 2015|