21 December 2007
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21
December 2007
VERSION: 1 2 3 4 5 6 7 8 9
21 December 2007
VERSION: 1 2 3 4 5 6 7 8 9
- Indemnification: The sponsor likes to
be held harmless for acts of negligence that the PI commits that are
solely the error of the treating physician. For example, if a PI treats a
subject's UTI during a study and the patient suffers an injury from this,
it is squarely the PI’s fault and it would not be proper for the sponsor
to sustain an injury by being held liable for it. However, we are aware of
a BP study where the PI followed the protocol and had the subject wash off
their BP medication and suffer a stroke from the lack of the proper BP
treatment. The sponsor forced the PI to use his medical malpractice
insurance to satisfy the claim for medical malpractice. Clearly, this was
an injustice as the PI was following the protocol precisely and even
though it is unusual for a stroke to occur during wash out, it certainly
does not immunize the subject from having a stroke. When a stroke occurs
during wash out it is important that the sponsor take responsibility for
the liability. This should be true of any injury ex officio of changing a
subject’s treatment while following the protocol. If this drug causes
respiratory depression, are you going to be fully liable?
- Study Fully Populated
Causing Premature Early Termination: As sites advertise for patients to
become research volunteers, the people that are good enough to step
forward to join, wash off of their existing treatment, come to our site
and devote a significant amount of their time with blood draws, signing
paperwork and allowing the experimental protocol to progress, should be
guaranteed that the sponsor will not prematurely shut down the study
because they have obtained the needed number of subjects. That is, it
should be the sponsor’s responsibility to do the number crunching early
enough not to allow subjects to sign consent and undergo early termination
just because the study is now considered full enough. This is not ethical
or in the patients best interest. All subjects who sign consent must be
allowed to continue thru the protocol if they are continuing to fulfill
criteria regardless of how many subjects are in the trial.
- Reimbursement for
Screen Failures: Sites are taking finincial risk in the name of enrolling only
those subjects who will successfully complete the trial. Sponsors need to
recognize that this significantly slows enrollment. When we see a subject
who may qualify but then again may not, we would be hesitant to enroll in
that study. Since the exclusivity clock starts clicking as soon as the
drug is patented it is imperative that the studies are done as quickly as
possible. Sites that are rewarded for each piece of work they legitimately
perform will have to enroll better. Sites with too high screen failure
rates can be turned off to ensure the proper motivation to enroll high
quality subjects is present.
- Initial Fasting Labs
and Informed Consent: Many trials have visit one with fasting labs and signing informed
consent on the same day. This is less desirable than having a visit one
where the subject presents non-fasting for the purpose of signing the
informed consent form and having the study discussed with them. The
potential problem is with a diabetic. If a diabetic patient answers an ad
and presents fasting for visit one, a research related procedure was done
prior to signing the ICF (Informed Consent Form). They could get a low
sugar reaction while driving to the site and suffer an MVA. They may also
feel pressured to sign the ICF quickly as they know when the do so they
will finally get something to eat. This can be most safely avoided by
allowing subjects to sign the ICF on a pre-visit one or by writing
protocols that don't have fasting labs as a visit one procedure. Although
I understand V1 labs are non-fasting for this trial.
- Recruitment: Too
often recruitment is an oversight thought to be the sites problem dealt with
at a time other than the beginning of the trial. It becomes the sponsor’s
problem after many sites under enroll. Wise sponsors address recruitment
up front at the investigator’s meeting and include recruitment agencies.
One budget neutral solution is for the sponsor to push to make available
an IRB approved ad for those using the central IRB at the very beginning
of the trial. In addition use of centralized recruitment agencies like Pi
and Acurian can very useful and cost effective. All our databases could be
larger. A small minority of people step forward to become research subject
volunteers. Planning for recruitment issues at the beginning is much
better than catch up at the end.
Investigator Meeting:
Maui