In my last post on this issue, I had written on the scope of situations, in which a clinical trial participant/subject is entitled to compensation for trial-related death or injury under the new Rule 122DAB of the Drugs and Cosmetics Rules, 1945 (“D&C Rules”) notified in January, 2013.
Sub-rule 5 of the same rule exhaustively lists the specific instances/causes which shall be considered to have caused clinical trial-related injury or death. They are as follows:
A. Adverse effect of investigational product(s)
B. Violation of the approved protocol, scientific misconduct or negligence by the Sponsor or his representative or the investigator
C. Failure of investigational product to provide intended therapeutic effect
D. Use of placebo in a placebo-controlled trial
E. Adverse effects due to concomitant medication excluding standard care, necessitated as part of approved protocol
F. For injury to child in-utero because of participation of the parent in the clinical trial
G. Any clinical trial procedures involved in the study.
Situation C which envisages payment of compensation in the event of injury or death due to “failure of investigational product to provide for intended therapeutic effect”, in my opinion, is unreasonable for it expects every clinical trial to succeed. After all, the very purpose of the trial is to evaluate the efficacy of the investigational product, and to saddle the Sponsor with a compensation for failure to succeed beats logic and common sense.
The inclusion of Situation C in the new Rule 122DAB is probably reflective of the Establishment’s need to appear to have taken stringent action, and to shore up its reputation after the rap it received on its knuckles from the Supreme Court last year. But in the process, the new Rule could have the effect of deterring Sponsors from undertaking clinical trials in India, thereby adversely affecting the fortunes of CROs in India, who already face stiff competition from China.
Apart from issues relating to Rule 122DAB, CROs in India seem to be of the opinion that the timeline prescribed for payment of financial compensation in Rule 6 of Appendix XII of the D&C Rules is impractical and unreasonable.
Under Rule 6 of Appendix XII, within 24 hours of the occurrence of a serious and unexpected adverse event, the Investigator must report the occurrence of the event to:
(a) the Drug Controller General of India (DCGI, the Licensing Authority under the D&C Rules),
(b) the Sponsor or its representative who obtained permission from the DCGI for the clinical trial, and
(c) the Ethics Committee.
Rule 6 prescribes two sets of procedures, one in the event of death, and another for injury.
Procedure in the Event of Clinical Trial-related Death
In the event of a clinical-trial related death, the procedure envisages the mandatory constitution of an Independent Expert Committee by the DCGI which shall submit its report on the cause of death and proposed financial compensation. The procedure does not throw light on the composition of the Expert Committee.
Within 10 calendar days of the death, the Sponsor/its representative and the Investigator shall each submit their own reports to (a) the DCGI, (b) Chairman of the Ethics Committee, (c) Chairman of the Expert Committee and (d) Head of the institution where the clinical trial was conducted.
Within 21 calendar days of the death, the Ethics Committee shall then forward its own report on the cause of death and opinion on the compensation to (a) the Expert Committee and (b) the DCGI.
Within 30 days (the procedure does not mention “calendar”) of receiving the report from the Ethics Committee, the Expert Committee shall examine the report and give its opinion on the cause of death and also recommend the quantum of compensation to be paid by the Sponsor/its representative. In formulating its recommendations, the Expert Committee may consider the report of the Investigator and the Sponsor/its representative.
Within 3 months of the serious event being reported by the Investigator (not from the receipt of the final report of the Expert Committee), and after considering the recommendations of the Expert Committee, the DCGI shall determine the cause of death, decide the quantum of compensation for and pass necessary orders.
Within 30 days of the receipt of the order passed by the DCGI, the Sponsor/its representative shall pay the compensation to the nominee of the deceased trial participant.
Procedure in the Event of Clinical Trial-related Injury
The timeline for the procedure in this situation remains the same, with the difference being that the constitution of an Expert Committee by the DCGI in the case of a serious event other than death is optional. Here too, the DCGI is expected to pass an order within 3 months of the serious event being reported by the Investigator, and payment of the financial compensation by the Sponsor/its representative is to be made within 30 days of receipt of the order passed by the DCGI.
Criticism from Stakeholders
Stakeholders are of the opinion that the window of 24 hours for reportage of Serious and Adverse Event (SAE) by the Investigator is unreasonable and that it takes longer to document and report the serious event.
The SAE report is to be prepared in accordance with Appendix XI of the amended Schedule Y. Under this format, apart from patient identification details, details of suspected drugs and other treatments, the Investigator is supposed to include the following:
“4. Details of Suspected Adverse Drug Reaction(s):
Full description of reaction(s) including body site and severity, as well as the criterion (or criteria) for regarding the report as serious. In addition to a description of the reported signs and symptoms, whenever possible, describe a specific diagnosis for the reaction.
Start date (and time) of onset of reaction
Stop date (and time) or duration of reaction
Dechallenge and rechallenge information
Setting (e.g., hospital, out-patient clinic, home, nursing home)
Information on recovery and any sequelae; results of specific tests and/or treatment that may have been conducted
For a fatal outcome, cause of death and a comment on its possible relationship to the suspected reaction; Any post-mortem findings.
Other information: anything relevant to facilitate assessment of the case, such as medical history including allergy, drug or alcohol abuse; family history; findings from special investigations etc.”
I am given to understand that given these details which need to be included in the SAE Report, 24 hours is inadequate. I am not sure of the rest of the timeline, but the 24-hour window does appear to cut it too fine.
It also appears that a section of stakeholders had advocated the inclusion of an arbitral mechanism to decide the quantum of compensation. But given the nature of the issue and manifest public interest involved, it is probably for the best that the Licensing Authority/DCGI has retained its jurisdiction over the issue. This also helps CROs, Sponsors and Investigators avoid allegations of exercising undue influence over the patient/his nominee or for short-changing the patient/his nominee in any manner under the garb of arbitration which would have been expensive and time-consuming for the patient/nominee.
Comments and Corrections are Welcome!
(Image from here)
(Image from here)