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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)
5.
Outcome
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)
