Training, Site Selection and Human Subject Protection: Factors to Consider When Developing a Monitoring Plan

Transcription

1 Training, Site Selection and Human Subject Protection: Factors to Consider When Developing a Monitoring Plan Cynthia F. Kleppinger, M.D. Senior Medical Officer Office of Scientific Investigations Office of Compliance Center for Drug Evaluation and Research US Food and Drug Administration

2 Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. ( DIA ), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. For work prepared by US government employees representing their agencies, there is no copyright and these work products can be reproduced freely. Drug Information Association, Drug Information Association Inc., DIA and DIA logo are registered trademarks. All other trademarks are the property of their respective owners. 2

3 Objectives Describe the monitor and staff training requirements, site selection criteria and human subject protection practices reported by CTTI survey respondents Discuss strategies to address these factors in a monitoring plan 3

4 ICH E6: Monitoring The determination of the extent and nature of monitoring should be based on considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial.

5 And E6 says In general there is a need for on-site monitoring, before, during, and after the trial; however, in exceptional circumstances the sponsor may determine that central monitoring in conjunction with procedures such as investigators training and meetings, and extensive written guidance can assure appropriate conduct of the trial in accordance with GCP. Statistically controlled sampling may be an acceptable method for selecting the data to be verified.

6 Survey Results: Training

7 Assess study staff's understanding of the trial protocol and procedures

8 Reality he-heavy-burden-of-protocol-design/articlestandard/article/detail/513703

9 Verify, in an ongoing manner, the adequacy of site staff (resources and training)?

10 What does ICH E6 say? Each investigator should be qualified by training and experience and should have adequate resources Verifying that the investigator has adequate qualifications and resources and these remain adequate throughout the trial period

11 Minimum level of education monitors are required to have

12 Require that monitors have a minimum amount of experience

13 Require that monitors have continuing education in clinical research/monitoring

14 What does ICH E6 say? Monitors should be appropriately trained, and should have the scientific and/or clinical knowledge needed to monitor the trial adequately. Monitors should be thoroughly familiar with the investigational product(s), the protocol, written informed consent form and any other written information to be provided to subjects, the sponsor s SOPs, GCP, and the applicable regulatory requirement(s).

15 Survey Results: Site Selection

16 What are the most important factors impacting site quality? Quality of training of the research coordinator in GCP, quality of study-specific training provided by sponsor Presence of a qualified clinical coordinator with sufficient time to perform the trial related duties, qualified staff, site staff turnover and capacity Design of the protocol, simplicity of the study, complexity of protocol and procedures, clarity of protocol Investigator: qualification and experience, dedication, motivation, oversight, commitment to excellence, time Monitoring staff quality and experience, quality and availability of the monitor, early engagement of the monitor at the site, company staff experience/knowledge

17 Rationale for conducting evaluation of site facilities Regulatory/GCP requirements, SOPs Facilities & equipment can directly impact trial conduct quality To ensure they are qualified to conduct the study at their site (appropriate staff/equipment to conduct study procedures, availability of suitable patients to enroll in the study, knowledge of GCP, etc.) Commensurate with high study risk

18 Selection of qualified investigators who have experience with intervention or condition

19 Required documentation is obtained from participating investigators (e.g. CV, financial disclosure, regulatory documentation)

20 Clinical investigator and staff are appropriately trained on protocol or investigational plan

21 Verify, in an ongoing manner, the adequacy of protocol-required facilities and equipment

22 Factor geographic location of sites

23 Survey Results: Human Subjects Protection

24 Adequate Protection of the Rights of Human Subjects

25 Assuring the Protection of Subject Safety

26 Assure subjects adequately informed about the trial

27 Assure ability to obtain informed, written consent

28 Assure ability to maintain ongoing communication with participants

29 Require evidence of subjects identification verification (e.g. photo ID)?

30 Assess Understanding of IC

31 If so, is it formal testing?

32 Rationale for Assessment of Consent If it is an IRB requirement Under-resourced to observe consent process and assess participant understanding Have not found a scalable way to have sites (willingly) test trial participant understanding of consents Unreliable tools have been problem as has been translation/cultural barriers to assessing patient understanding of information

33 Back-translation of IC

34 Good News Does your organization confirm site informed consent forms are updated/modified when necessary: Always 91%

35 Conduct an assessment of risk prior to developing a monitoring plan for each protocol

36 Mapping Thoughts to Actions Evaluate critically monitor selection. Is it rationale. Is it consistent. What went wrong in the hiring of a poorly performing monitor? Is that monitor really qualified and well-versed on the protocol to be the only resource/teacher to site staff? How is GCP training at the site evaluated by the monitor?

37 Oversight of Monitors Are the staff truly qualified to critically read and assess the monitoring reports? Is anyone cross-checking the reports? Are you critically looking at poorly written reports to assess the reason? Are there on-site evaluations by supervisors and are they consistently done?

38 Site Selection Who is really making that decision and does the rationale map to your quality expectations? Have you critically reviewed a wrong site selection and corrected the reasons why it got selected? Are you reviewing the quality of the site staff? Are you re-assessing?

39 Human Subjects Protection Are your values being reflected in your actions? Are you really addressing the issues that come with the globalization of clinical research?

40 Final Thoughts A risk-based approach can only occur if the foundation is solid. Quote by EU inspector on a conference call Risk assessment is not the same as gambling.

41 Thank you for your attention.