Clinical Researcher—April 2019 (Volume 33, Issue 4)
Elizabeth Weeks-Rowe, LVN, CCRA
There are fundamental steps a physician who is interested in conducting clinical research can take to best prepare for his or her new role as a principal investigator (PI). These tasks are integral to understanding such research tenets as patient safety, critical data, and investigator oversight. These activities will help a new investigator discriminate between clinical research and clinical practice, which can be a stumbling block in the overall assimilation to clinical research. Finally, these steps will demonstrate the investigator’s due diligence in familiarizing with ALL responsibilities required for successful study conduct, and will give them a competitive edge (despite being new) when being evaluated for study participation.
To best prepare for the PI role:
1. Engage in complete, comprehensive Good Clinical Practice (GCP) training from a reputable industry vendor and/or a source recommended by an experienced research colleague. There are many credible online programs; however, this training should include more than basic human subjects protection by covering such topics as GCP, informed consent, institutional review boards (IRBs), investigator responsibilities, safety reporting/adverse events, investigational product handling, the Health Insurance Portability and Accountability Act, records/source document processes, and financial disclosure. This is not an all-inclusive list, but rather a guideline to ensure new investigator GCP training encompasses all required, impactful components of clinical trials.
2. Consider additional PI training; there are several online and/or classroom courses that include important, “behind-the-scenes” elements of the PI role, such as administrative and financial planning and strategizing for patient recruitment (i.e., other things critical to the PI role, outside the basic, participant-facing PI tasks).
3. Familiarize yourself with key portions of the Code of Federal Regulations: 21 CFR 50 (informed consent), 56 (IRBs), 11 (electronic records), 54 (financial disclosure), 312 (Investigational New Drugs), 314 (applications for U.S. Food and Drug Administration [FDA] approval to market a new drug).
4. Familiarize yourself with the International Council for Harmonization E6(R2) Guideline for GCP.
5. Familiarize yourself with the following FDA guidanances/information sheets (this is not an all-inclusive list—there are many insightful documents on the FDA website):
- Information Sheet Guidance for Institutional Review Boards (IRBs), Clinical Investigators, and Sponsors
- A Guide to Informed Consent
- Exception from Informed Consent Requirements for Emergency Research
- Recruiting Study Subjects
- Using a Centralized IRB Review Process in Multicenter Clinical Trials
- Oversight of Clinical Investigations: A Risk-Based Approach to Monitoring
- Use of Electronic Informed Consent: Questions and Answers
6. Review the FDA website for the contents of Warning Letters to familiarize yourself with what items are under specific scrutiny by the agency during an audit, and what are integral areas of compliance (https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm).
7. Align with an experienced PI for additional guidance, for such things as conduct of the first screening/baseline study visit for a subject, appropriate informed consent conduct/process, appropriate PI oversight, best training/communication practices for a research department, how to pick appropriate sub-investigators, etc. A strong mentor is imperative when learning to manage clinical trials, investigative staff, and patient safety.
8. Hire an experienced study nurse, study coordinator, or research administrator to facilitate the complicated regulatory and fiscal documentation associated with site activation and clinical trial conduct. Trying to expedite study start-up activities (contracts/IRB submissions are complicated enough for an experienced researcher) with a novice coordinator may set the investigator up for additional errors and submission delays. If both the PI and research coordinator/study nurse are new, it is critical to have an experienced research colleague or consultant to facilitate the activation process and meet the rapid and stringent timelines for study start-up chores.
During site selection:
1. During a pre-study/site evaluation visit, transparency is key regarding research experience. The investigator should disclose his/her new investigator status on feasibility questionnaires and to the clinical research associate (CRA) assessing the site. This honesty creates a platform from which investigators can stand out and strengthen their status by:
- capitalizing on all efforts to prepare for their role and thus study success;
- producing all documentation of training completed during their familiarization;
- informing the CRA of alliances with other experienced investigators to further understanding of investigator tasks/responsibilities; and
- hiring experienced study staff to support the activation and overall assimilation process.
2. Ensure the investigator’s CV reflects any study experience (in preclinical settings, as a sub-investigator, etc.), therapeutic expertise, and all study training completed.
3. Demonstrate access to the study population with redacted database reports of potential study patients. This can be done via a specific search from a practice database or a clinical trials management system.
These steps do MATTER, and following them will help mitigate any unease felt (by the sponsor) regarding a PI’s inexperience. A key factor to remember is that diligence, follow-through, integrity, and enthusiasm are strong investigator traits, and are not limited to those with research experience.
Elizabeth Weeks-Rowe, LVN, CCRA, (email@example.com) is a principal clinical research associate in study start-up based in San Diego, Calif. She last wrote for Clinical Researcher in January 2019’s “Hindsight, Foresight, and Coming Full Circle.”