For Pharmaceuticals and Biotechnology
In the last decade, clinical researchers have conducted clinical trials where their lack of knowledge of human subject protections embodied in Good Clinical Practices and ethical conduct for research (Belmont Report, Declaration of Helsinki) has resulted in clinical trial misconduct and subject deaths. Notably, these cases were reported in both our news media and professional publications.
These cases, Jesse Gelsinger (1999, University of Pennsylvania, Gene Therapy Program) and Ellen Roche (2001, Johns Hopkins Hospital), were inspected by both the FDA and the Office of Human Research Protections (OHRP) with the identification of a broken system of clinical research oversight and human subject protection. These findings document that our 'System of Shared Responsibilities' was gravely broken at these institutions. Granted, since these occurrences, these issues have been addressed by both institutions; however, the 'broken systems' could have been prevented with proper training on human subject protections, GCP training and additional topics.
Since these landmark events, clinical researchers continue to misunderstand their responsibilities and how to implement these responsibilities in clinical trials. Hence, we continue to see institutional and investigational site regulatory inspections identifying significant issues in the conduct of clinical research.
Clinical Research Training Equal to Medical PracticeEstablishing mandatory training for clinical research does have precedent in both U.S.-based medical practices and the U.S. product development regulations. Firstly, in the U.S. Code of Federal Regulations, training and training documentation are requirements in both Good Manufacturing Practices (21 CFR 201 and 210, QSR) and Good Laboratory Practices (21 CFR 58) for the activities and personnel employed in these non-clinical specialties. It is now time to bring the same level of requirements, standards, and performance to the GCP arena, which is much closer to ensuring subject safety than the production of investigational products and animal studies.
As a Registered Nurse, my nursing school training was multi-tiered before I was allowed to take a patient's vital signs, administer a medication, administer shots, perform venipunctures and take a patient's intake history for their medical record. This training including the following:
Therefore, clinical researchers need to be approaching clinical trials, and the care of our study participants—the 'subject'—as equal to medical practice and ensure that professionals designated to 'care for our subjects' are trained to the same standards as non-clinical research subjects (e.g. medical practice, clinics etc). Would a physician/PhD/dentist/nurse practitioner in private practice actually delegate these responsibilities to unqualified staff per state licensure requirements and professional liability standards? I believe not.
On the Job Training Critical for Subject SafetyAs a professional who has held positions as a Research Nurse, Clinical Research Associate (CRA), Clinical Trial Manager, as well as in Clinical Compliance - Standards and Training, and Clinical Research Training, I continue to be concerned at the inadequate knowledge and lack of practical training (how are staff trained to obtain informed consent, identify and report AEs/SAEs, perform study procedures, review an Investigator's Brochure for safety profile review, documentation, etc.), for institutions, IRBs, investigators, sub-investigators, study coordinators and study personnel ranging from standalone private practices to academic institutions. In the training of our health care professionals, the educational approach includes self-study, classroom learning and on-the-job-training. However, with the emergence of online/e-learning/computer-based training, many people believe that completion of such learning modules state that they are trained and qualified to conduct their role in clinical research. However, without the inclusion of on-the-job training, such online learning is merely the same as 'reading a textbook'. Such a training practice for either a doctor or a nurse would not be viewed as resulting in a competent skill level for patient care (i.e., qualified to care for the patient on the topic being 'read' online alone). Therefore, the industry needs to reconsider current methods and paradigms in educating and training clinical research personnel; specifically, the inclusion of 'on-the-job training' on specific topics and training documentation (i.e., training plans/curricula and training records) for deeming personnel 'qualified' to perform their assigned duties. (Wool, June 2008, Monitor magazine).
ConclusionRecommendations for training have been noted in OHRP Determination Letters and FDA Warning Letters over the past few years (e.g., GCP, investigator responsibilities, adverse events, case histories, investigational product management and accountability, informed consent, staff training on protocol/study procedures, corrective and preventive actions for errors in research execution, etc.). Requiring mandatory training for institutions, investigators, IRBs and study staff engaged in clinical trials and under the purview of GCP can be substantiated and benchmarked to current requirements in the U.S. CFR for GMP and GLP regulations, as previously discussed. This level of regulatory requirement is needed as well in the GCP arena. Clinical researchers governed by GCP are actually 'closest' to the care of the study subject of all three of these specialties (GMP, GLP, GCP); why not bring their training standards and requirements up to the same level as GLP and GMP?
Carneval AP, Gainer LJ. 1994. Trends in training on the job. Technical and SkillsTraining, p. 10 16.
Dubois D. 2004. Competency-based or a traditional approach to training? Training andDevelopment, p. 46-56.
Gupta, K., Sleezer, C. M., Russ-Eft D. 2007. A Practical Guide to Needs Assessment. San Francisco
Main R. 2002. Human Performance Essentials. Alexandria, Va.: ASTD Press.
Wool, Liz, Good Training Practice 101: A Primer for Employee Training Plans, June 2008, Monitor magazine, ACRP, Alexandria, Virginia
FDA Code of Federal Regulations: 21 CFR Part 58 Good Laboratory Practices; 21 CFRPart 211 Good Manufacturing Practices.
21 CFR 312 Investigational New Drug Application,
ICH E-6 Good Clinical Practices Guidelines.
21 CFR 812 Investigational Device Exemptions
About the Author
Liz Wool possesses 19 years in the product development industry inclusive of positions in biotech and pharmaceutical companies, investigational sites, CROs, and academia. This experience includes drugs, biologics and medical device clinical research. She has presented at industry meetings on clinical quality systems and Good Clinical Practices (GCP) for numerous professional organizations and industry training providers including the Association of Clinical Research Professionals (ACRP), Drug Information Association (DIA), Society of Quality Assurance and FDANews. She is also a faculty member for ACRP teaching the CRA and CRC Certification Exam Review Courses.
Liz's expertise is unique in that she has held positions as a Research Nurse at Johns Hopkins Hospital in Baltimore, Maryland, site monitor (CRA), CRA manager, study manager, Sr. Manager, West Coast Learning and Development, Head, Clinical Research Training, as well as, director-level positions in Clinical Compliance and Clinical Operations. This experience has been obtained through positions at Gilead, Quintiles, Johnson and Johnson Pharmaceutical Research and Development, Scios and The Henry M. Jackson Foundation. This comprehensive experience provides her with the ability to understand both the conduct and management of clinical trials from the site and sponsor perspective thereby providing consulting support that is global and comprehensive in nature. Her experience in quality systems development and management coupled with her experience with internal and external regulatory inspections (MHRA, FDA) and CAPA 'solutions' for her assigned departments influences the global focused 'solutions' that QD-Quality and Training Solutions, Inc. provides to our clients.
She holds faculty appointments at the University of California, Berkeley, University of California, Santa Cruz and San Francisco State University in the Clinical Research Conduct and Management Certificate Programs as well as serving as a Program Advisor to the UC Berkeley program. She volunteers her time to the Association of Clinical Research Professionals (ACRP) by serving as President of the Northern California Chapter, Editorial Advisory Board, ACRP Monitor Magazine and Member- Global ACRP Membership Committee. Liz's article, Good Training Practice 101: A Primer for Employee Training Plans was published in the June, 2008 Monitor magazine, for the Association of Clinical Research Professionals (ACRP).