Show Me the Documentation

Clinical Researcher—March 2019 (Volume 33, Issue 3)


Jan S. Peterson, MS, CCRA, RAC, ASQ CBA, ACRP-CP

Q: My institution is currently in the process of amending its standard operating procedure (SOP) for CITI Program training. We have been having trouble keeping key personnel compliant, and are wondering what the federal requirement is for training in research. I was under the impression that training in Good Clinical Practice (GCP) and human subjects protection (HSP) was required, but another member on my team thinks only GCP is required. I am not able to find any guidelines/regulations that specify exactly which training is needed.

A: Even a diligent search for specific U.S. Food and Drug Administration (FDA) “requirements” for GCP and HSP training will not provide a clear answer, as there are none. Don’t be shocked! Even the broader Common Rule (45 CFR 46 in the Code of Federal Regulations), in effect at all federally funded institutions like universities and most hospitals, says nothing about specific investigator training requirements for clinical research activities. If you are conducting clinical studies funded by any institute in the National Institutes of Health (NIH), there is a Human Subjects Education Policy that requires individuals involved in the design or conduct of the studies (i.e., “key personnel”) to receive education on the protection of human subjects. But the institution that receives the grant or contract must determine what is adequate to meet the education requirement, and NIH does not specify or endorse any particular program. The U.S. Department of Health and Human Services, under which both NIH and FDA are organized, has a directive that calls for “appropriate research bioethics training and human subjects research training” for investigators, but again, no specifics about what is appropriate are provided.

However, there is a recognized cascade of responsibilities for documented training that do stem from specific FDA regulations and guidance documents, including the International Council for Harmonization (ICH) E6(R2) Guideline for GCP, which is endorsed by the FDA. In addition, there are what some would call accepted “industry practices” not published by FDA or ICH. For example, you may find the TransCelerate Biopharma “Minimum Criteria for ICH E6(R2) GCP Investigator Site Personnel Training” document as a useful resource, but I reiterate that those criteria do not constitute a regulatory requirement.

Comprehensive GCP training often covers most, if not all, of the topics many also consider as HSP (or what CITI refers to as Human Subjects Research, or HSR) training. So, you have to see the various course curricula to assure you are getting what you want/need without unneeded overlap. Separation of GCP and HSP/HSR courses can be useful to isolate topics more useful for different personnel, and also to break up the learning modules into more digestible portions.  Many institutions have their own requirements, of course, independent of commercial clinical study sponsors. This is most common at institutions like universities and hospitals receiving federal funding, and the relevant institutional review board (IRB) for the institution may provide (or at least review) the specific minimum education requirements.

If you start with regulatory obligations, all sponsors of FDA-regulated clinical studies are responsible for “selecting qualified investigators” (see regulations at 21 CFR 312.50 as a base starting point for drug studies; medical device studies have parallel regulations to quote, like 812.43(a)). At 312.53(a) a bit more detail is given, as drug study sponsors “shall select only investigators qualified by training and experience as appropriate experts to investigate the drug.” Not so helpful yet, right? What training? What experience? What is an “expert”? What about everyone else on the research team?

Note: If you prefer the ICH E6(R2) GCP citations (I often do), please look at Sections 2.8, 3.2.1 (for IRB members), 4.1.1, 5.0.4 (this section is new in the E6(R2) update and here the “risk control” concept is noted as a sponsor decision process), 5.5.3(b) Addendum (for computerized systems), 5.6.1, 5.7, 5.18.7 (also an R2 update section), and 5.19.2(b) (which relates to auditors). If you/your sponsor claim to be following GCP (it probably says this in most protocols or the sponsor’s SOPs), then you have to consider what it says in these GCP sections about training and experience for study personnel.

Back to the FDA obligations: What is meant by “qualified,” being an “expert,” or “training and experience” is not detailed in the regulations, GCP, or in FDA guidance. Nor is what might be considered specifically as adequate documentation for these (other than in an investigator’s CV “or other statement of qualifications” as quoted in 312.53(c)(2)).

So, we (i.e., everyone in the clinical research enterprise) all are faced with both determining what is appropriate training for study personnel (like, just the basic concepts or more of the details of GCP, HSP/HSR, and research ethics) and how to document that training so someone else can evaluate it upon review—and hopefully they will then consider it adequate. (The contemporary approach is to use “risk-based” methodologies to assess and plan for your training/documentation requirements. That’s a longer and separate discussion, though in reality, everyone has always been using risk-based methods to some extent, whether they called them that or not.)

Further on in the FDA drug regulations at 312.53(c)(1)(vi)(g), an investigator’s responsibility is extended to the study team, as the investigator will “ensure that all associates, colleagues, and employees assisting in the conduct of the study(ies) are informed about their obligations…”. This “ensuring” part, as well as the need for them to be “informed,” is what most recognize as creating a generalized training requirement for study personnel at the site level.

Now, exactly what constitutes adequate training to “ensure” things will be done right (you know, things like the sponsor’s and investigator’s obligations to conduct the study according to the investigations plan and protect the rights, safety, and welfare of study participants, etc.) and what constitutes adequate documentation for this, is in general left to the sponsor and investigator, respectively, or according to the institution’s policies. Some would say ultimately this always rests with the study sponsor. Fine—and many commercial sponsors (and institutions) will tell you explicitly what they consider “their” requirements for training and the requisite documentation.

Sponsors and contract research organizations (CROs) should not be claiming their specific training requirements are “FDA requirements” per se (as I mentioned, these are nonexistent), but they certainly can be the institution’s, sponsor’s, or CRO’s own requirements. Each party must consider how others (in particular, FDA or other regulatory body inspectors, monitors, and auditors) will look at this training issue through some future review of documentation as they seek evidence that the involved study personnel were indeed trained and qualified to perform their study-related activities. It’s always a “show me the documentation” situation.

Depending on the role of the study personnel (investigator, receptionist/scheduler, nurse, physician, scribe, coordinator, data clerk, technician examiner, clinical lab chemist, research lab chemist, pharmacist, IRB member…the list is quite long) someone needs to evaluate what aspects of GCP and HSP/HSR, in addition to protocol-specific instructions, are needed to meet the “ensuring” target for those various personnel. Some sponsors take a broad approach (perhaps unnecessarily so) and say “everyone at the site involved in our study needs comprehensive GCP and HSP/HSR training” and it must meet minimum criteria for the training time commitment and obtaining a passing score on some evaluation. Other sponsors are willing to scale the requirements according to levels of responsibility, roles, or involvement.

Perhaps the training needs to meet some “industry standard,” like a curriculum outlined by TransCelerate or another body, or be sourced through specific vendors, like CITI, or through the institution. Even if you use CITI, many participating institutions can and do tailor the basic CITI GCP course modules collection (by addition or subtraction of specific modules) making their GCP course institution-specific.

Some sponsors give no useful instructions for training at all. Other sponsors may direct investigators to be more selective (as some FDA guidance documents suggest) and focus more comprehensive training on “key personnel” (as NIH policy implies) who really need a stronger, more comprehensive GCP and HSP/HSR training experience. This routinely applies to the lead investigator and their coordinators, most subinvestigators, and the research pharmacist. Policies may allow those in other, less research-responsible roles at the site to receive less comprehensive GCP training but keep at least the HSP/HSR privacy modules if they handle the research data or subject medical charts, for example.

How sponsors/investigators/institutions choose the type and extent of the training they require for site study staff is also an enforcement issue, to be sure. Does training ever expire? Is re-training needed at some interval? For which staff members? Why? (I had someone ask me once if re-training was needed to update training documentation that had just expired after all the last study visits were completed and close-out was occurring. I said no; be sensible.)

Not all sponsors are very good about explaining their desires and requirements clearly (through SOPs or the investigator contracts, for example). So, when monitors report that staff training and the related documentation are inadequate, what is to be done? What standards are being applied to judge noncompliance? Whether training is completely lacking or perhaps out-of-date, we know sponsors are still stuck with their obligations to bring sites back into “compliance.”

Compliance, it should be noted, has two primary masters: regulatory compliance for FDA and compliance with the sponsor’s own SOPs (and often the site’s SOPs, as well) and protocol. Few sponsors are very good at the compliance side of this issue, despite their monitors’ reports describing lack of adequate and documented training or re-training for study staff, assuming the requirements were clear to begin with.

When sites are noncompliant with the stated training requirements, the hammer never seems to fall often enough on the investigator/site in a way to risk investigator payments from the sponsor, or stopping shipments of study drug and termination of study participation at the site. (This is about the only leverage the sponsor really has, according to the regulations at 312.56(b). Institutions may have other enforcement options, as does NIH.) I’m complaining here, but in my opinion, this section of the regulation is exercised too rarely by sponsors. Perhaps because their investment has already been high, clearly many noncompliant sites are allowed to continue on in a state of noncompliance for a variety of reasons (not just lack of appropriate training, to be sure).

I’ll stop here. As you can see, the sponsor and/or the institution should be driving this training/training documentation issue using clear, written requirements. I hope sponsors in particular (perhaps through their CRO and monitors) provide reasonable instructions about their “requirements” for investigator and relevant staff training, in advance, and are willing to enforce what they consider really necessary for study quality, safety, and overall ethical human research. I also hope sponsor requirements are thoughtfully considered (in conjunction with any institutional policies), and not so onerous for everyone at a site that they inhibit qualified investigator participation in clinical research.

I have observed (as perhaps you feel) that many investigators and research staff are not provide adequate time for GCP and HSP/HSR training, or are somehow resistant to re-training, as our question writer noted. But if research staff, including the investigator, are not given (or refuse to accept) adequate time to be trained properly, I feel the site in general should not become a research site. You can base this decision on the need for sites to have adequate resources (see ICH E6(R2) GCP Section 4.2), which includes not only the necessary facilities but also having properly trained personnel. This commitment to adequate training is a part of the high (but necessary) costs of time and expenses associated with clinical research, and something that must not be ignored by sponsors or investigators.

In Conclusion…

As I have mentioned in other writings, being a good study site with qualified investigators and staff requires a significant expansion of understanding, skills, and procedures beyond the “good clinical practice” associated with routine clinical care. Good Clinical Research Practice (GCRP) is the way we should think of the clinical research endeavor, and as the complexity and regulatory controls for GCRP continue to increase, what we now call GCP and HSP/HSR training becomes even more important each year.


Some of the above details on training requirements and the role of IRBs were adapted from information posted to the ACRP Online Community by Erica Heath, MBA, CIP, in response to the author’s feedback on an Open Forum thread which serves as the basis for this column.

Jan S. Peterson, MS, CCRA, RAC, ASQ CBA, ACRP-CP, ( is a consultant and Vice President of Regulatory Affairs and Quality for Global Regulatory Partners, Inc., and a former Chair of the ACRP Regulatory Affairs Committee.