Good Clinical Practice: A Question & Answer Reference Guide - May 2018 - 40

GCP: A Question & Answer Reference Guide
A. This is an interesting question that comes at an equally interesting point in the evolution of clinical trials.
At the very time that the FDA is suggesting that industry sponsors must do more to verify the qualifications of
clinical investigators and others involved in their clinical trials (even in their home countries), drug companies are
using increasing numbers of clinical investigators and trial sites in "nontraditional" markets, in which they might
understand less about local qualifications and medical degrees. This issue was even acknowledged in a November
2009 speech by the Deputy Commissioner for International Programs Mac Lumpkin, MD, M.Sc., in which he
conceded that the globalization of clinical trials has made "assessing qualifications" more of a challenge in which
there must be "increased knowledge of various medical qualifications and medical practice legislation."
In a November 2009, informal response to this question, the FDA stated that, "as you note, it is left to the sponsor
to determine the necessary qualifications for an individual to conduct a particular study. However, FDA regulations
do impose a requirement on sponsors to choose clinical investigators qualified by training and experience (21
CFR 312.53(a) and 812.43(a)). This is important for studies conducted in the US as well, where we have seen
that inappropriate investigators do conduct studies if sponsors are not truly diligent in setting and maintaining
appropriate requirements. If international studies are not conducted under FDA regulations, there is still a need to
choose appropriate investigators, as acceptance of data for review in support of research and marketing applications/
submissions from non-US sites is dependent on the sponsor ensuring the proper conduct of the study. With studies
increasingly international in scope, the burden to determine who is qualified becomes more difficult as you say.
That is why sponsors need to carefully consider these issues before choosing to place a study in a new country/area.
"As you are aware, there is presently no FDA guidance relevant to this area. Therefore, sponsors need to be
guided by common sense approaches. Collecting information from countries as to the minimum requirements
for licensing for personnel to perform various levels of medical procedures/examinations would seem to be the
first step when it comes to determining investigator qualifications. In areas where education/licensing/certification
may be from across national boundaries, increased efforts may be necessary to collect such information from
several neighboring countries prior to inquiring about staff in a clinic/medical center that a sponsor is considering.
Sponsors can also hold pre-study conferences where study specifics are explained and an opportunity to ask
carefully fashioned questions of the potential study staff can reveal much about their knowledge and expertise.
Collaboration of site personnel with medical staff educated and/or licensed in countries with established medical
credentials is another factor to consider."
While the FDA acknowledges that the effort and resources necessary to verify the qualifications of clinical
investigators and staff in certain countries may undermine some of the short-term advantages of conducting trials
in those locations, the agency maintains that the effort is necessary. "These, like any innovative methods, require
time and expense upfront, when at least part of the incentive to conduct studies internationally is the lower cost and
broader subject base available," the agency noted in its response. "However, it would seem [to be] the only way a
sponsor can hope to determine who is qualified and thus most likely to conduct studies that will be acceptable for
review by FDA."
2.3

Q. Can non-physicians, such as Ph.Ds., Pharm.D.s, DOs, or DDSs, be considered qualified to serve as
principal investigators?

A. The FDA has answered this question on many occasions in the past. "The regulations do not require that the
investigator be a physician," the agency confirmed in addressing this question most recently-in a May 2010
guidance titled, "Frequently Asked Questions-Statement of Investigator (Form FDA 1572)."
Although the FDA's GCP regulations make no reference to a medical degree or other specific education or
training necessary to qualify as an investigator, the ICH GCP guideline is somewhat more definitive. In Section
2.7 of "The Principles of ICH GCP," the guideline states that "the medical care given to, and medical decisions
made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a
qualified dentist."
In recent informal correspondence on this question, the FDA stated that, although a clinical investigator need
not be a physician, such cases have implications for the qualifications of other individuals involved in the study.
"While technically a non-physician can be a principal investigator, this requires that the non-physician be qualified
to personally conduct or personally supervise all aspects of the study. In practice, we have found it very rare that a
non-physician can comply with this requirement. In general, where we have seen non-physicians listed on the 1572
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Table of Contents for the Digital Edition of Good Clinical Practice: A Question & Answer Reference Guide - May 2018
