Good Clinical Practice: A Question and Answer Guide2024/2025 Edition - 44

GCP: A Question & Answer Reference Guide
regarding disposition of the product under study, to attempt to find out why a subject has stopped coming to the
study site for his/her scheduled visits.
" There may also be specific reasons as to why it might NOT be advisable for a subject to abruptly terminate his/
her participation in a study. For example, would sudden discontinuation of the study product pose risks to subjects?
Do alternative therapies need to be considered or arranged for any subjects who discontinue the study drug? In such
cases, attempting to contact the subject may be more urgent. (Of course, any such circumstances in which it might
not be advisable for a subject to abruptly terminate use of the product under study should be clearly stated in the
informed consent document signed by and given to the subjects.)
" FDA's official guidance, the ICH E6 'Good Clinical Practice: Consolidated Guidance,' also supports delving
further into a subject's withdrawal. ICH E6 states in section 4.3.4: 'Although a subject is not obliged to give his/
her reason(s) for withdrawing prematurely from a trial, the investigator should make a reasonable effort to ascertain
the reason(s), while fully respecting the subject's rights.' "
In its informal response, the agency notes that, " at the very least, it would be reasonable to attempt to contact a
subject at the last known address/telephone number. However, there is no official guidance on methods to be used
in attempting to contact study subjects (e.g., phone calls, registered mail, e-mail, visit to the subject's address by a
social worker), nor is there guidance on the number of times that such attempts should be made before the subject
is 'lost to follow-up.' Clinical trial sites, thus, may develop (and follow) their own procedures to follow up with
subjects who miss study visits or seem to have dropped out of a study. "
Typically, the industry standard for addressing subject dropouts involves the following:
* Documented phone calls to the subject; the phone log should describe the outcome of these calls (e.g., " left
message on recorder " ).
* A certified letter (with return receipt requested) sent to subject; the letter should express the site staff's concern
for the subject's well-being.
* A subsequent certified letter sent to subject stating that he or she has been officially dropped from the study;
the letter should specify if the subject has any further obligations, such as returning unused study medications.
Some study coordinators go even further in attempting to contact potential dropouts. They visit the subjects'
homes, hoping to have a face-to-face discussion about the situation. Unannounced visits to the subject's home may
carry certain risks, however. A mutually arranged home visit to perform a check of vital signs and collect unused
study medication is probably less risky but suggests that the subject probably could have come to the study facility
for a visit.
Some study coordinators attempt to negotiate with potential dropouts over the phone. In some cases, the offer of
carfare or childcare removes an obstacle for a return visit and prevents an unnecessary dropout. In other cases, it is
helpful for the principal investigator to discuss the situation with the subject.
There is one other circumstance that should be considered when discussing potential dropouts: If the subject in
question has experienced an unresolved serious adverse event, this subject's clinical course must be followed to its
resolution. The same principle applies for pregnancies that occur while on study. In both instances, the site must
make every reasonable effort to obtain medical records and ensure the subject's safety.
2.27 Q. What type of documentation should an investigator maintain related to delegation of specific duties to
other members of the study team?
A. ICH E6 (R3) Draft states that " the investigator should ensure a record is maintained of the persons and parties
to 474 whom the investigator has delegated significant trial-related activities. In situations 475 where the clinical
trial activities are performed in accordance with routine clinical 476 care, delegation documentation may not be
required. " The MHRA Good Clinical Practice Guide states that in order to properly document they have authorized
appropriately trained and qualified individuals to perform certain trial related tasks, a delegation of authority log
is used. In the EMA GCP Q&A forum, an informal question was asked related to the investigator responsibility in
addressing situations where contractors undertake some investigator responsibilities. The EMA responded " great
care is ... needed in ensuring that the distribution of tasks is clearly documented and agreed, that each party has the
control and access to data and information that their legal responsibilities require and that the ethics committees
and regulatory authorities approving trials have been properly informed of these activities as part of the clinical
trial application process.
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Good Clinical Practice: A Question and Answer Guide2024/2025 Edition

Table of Contents for the Digital Edition of Good Clinical Practice: A Question and Answer Guide2024/2025 Edition