Responsible Research A Systems Approach to Protecting Research Participants (2003) / Chapter Skim
Currently Skimming:
5 Improving Protection Through Oversight and Data and Safety Monitoring
5 Improving Protection Through Oversight and Data and Safety Monitoring
Pages 136-161
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 136... ...
to be named and referred to within research organizations by a title reflective of their focus on the ethics underlying participant protection activities. The committee has adopted the term "Research Ethics Review Board" (Research ERB)
|
From page 137... ...
to direct IRBs, investigators, and sponsors in reporting and evaluating adverse events, confusion remains. Moreover, other entities not consiclereci in the fecleral regulations, such as Data and Safety Monitoring Boards/ Data Monitoring Committees (DSMB/DMCs)
|
From page 138... ...
Plans and resources for data and safety monitoring within an individual study should be commensurate with the level of risk anticipated for that particular research protocol. This chapter aciciresses the following topics surrounding the protection program's responsibilities for oversight and data and safety monitoring: government, industry, and local oversight; internal tracking mechanisms; data and safety monitoring within the program; the role of the Research ERB; clata security; privacy and confidentiality provisions; reporting information to participants; .
|
From page 141... ...
, which was created in 1972 within NIH and charged with the protection of research participants involved in all DHHS-funded research, including NIH's intramural and extramural research programs. In Tune 2000, OPRR was replaced with OHRP, which was moved out of NIH and charged with protecting human research subjects in biomedical and behavioral research across DHHS and other federal agencies that follow the Common Rule (DHHS, 2000b)
|
From page 142... ...
Other OHRP initiatives include a new system for IRB registration, a quality improvement program directed to research organizations, and the sponsorship of the Award for Excellence in Human Research Protection.5 The latter two initiatives are particularly significant, as they represent a shift in the manner that OHRP and its predecessor agency, OPRR, have traditionally conducted business. Although ensuring compliance through monitoring and site visits is essential to maintaining the integrity of the system, to maximize its impact, OHRP should expend more resources on facilitating the work of protection programs to meet compliance goals.
|
From page 143... ...
found that half of the IRBs seldom or never reviewed interim reports from investigators (Cooke and Tannenbaum, 1978~. The National Commission recommended, at a minimum, annual continuing review for research studies involving more than minimal risk or vulnerable populations (1978~.
|
From page 144... ...
The most extensive system of data and safety monitoring exists in the area of clinical trials subject to FDA review and approval. FDA inspects investigators, IRBs, and occasionally sponsors, to verify compliance with GCP.
|
From page 145... ...
To improve the Research Ethics Review Board's (Research ERB's) capability to oversee participant protection, the committee recommends that any monitoring report for studies under a board's purview be shared with that board.
|
From page 146... ...
ERBs to also see the investigator's response to the deficiency warning (and that of the research organization, as applicable) , as the response often sheds light on the inspection findings and clarifies how future problems can be averted.
|
From page 147... ...
. Sponsors regularly monitor investigator compliance with GCP and with specific study protocol, including the degree of participant protection achieved.
|
From page 148... ...
Pharmaceutical companies, or a CRO acting on behalf of the sponsor, generally send monitors to visit each participating site every 6 to 10 weeks to monitor the progress of the study, verify the accuracy and completeness of data submitted in case report forms, and assess investigator compliance with regulations and GCP. The Need for Collaboration and Harmonization of Federal Monitoring Activities Although FDA retains its enforcement authority for participant protect~ons in FDA-regulated drug, biologic, and medical device clinical trials, it is hoped that the increased centralized oversight provided by OHRP will lead to more consistent and effective guidance in human participant protections across federal agencies.
|
From page 149... ...
The appreciation and recognition of adverse events is particularly important in the context of clinical research, specifically in early phase clinical trials when little is known about the action of a test compound during initial exposure in humans and the determination of the safety profile is a critical marker. Indeed, the recognition and reporting of adverse events, coupled with appropriate intervention strategies, may constitute the most important function for research personnel in protecting research participants from harm and the population at large from subsequent exposure to a toxic or dangerous device or agent.
|
From page 150... ...
Training in these areas should be offered as part of an institution's ongoing continuing education program for relevant research staff, as only research staff that have the appropriate training and education should be evaluating research participants for adverse events. Clinical investigators should receive specific instruction about assigning a causal relationship of an adverse event to the drug, biologic, or device under investigation; Research ERBs should be provided guidance on how to interpret and respond to such reports; and clinical trial participants should be instructed on how to recognize and report adverse events to study personnel.
|
From page 151... ...
NIH's Office of Biotechnology Activities oversees gene transfer clinical trials through its management of the NIH Recombinant DNA Advisory Committee, which ensures additional safeguards on the conduct of gene transfer clinical trials. The committee endorses NIH's requirement for DSMPs for all clinical trials, and further supports its extension to all studies involving more than minimal risk.
|
From page 152... ...
The investigator is responsible for ensuring that any study conducted is scientifically sound and implemented according to standards of ethical conduct and, as appropriate, GCP, by a trained and knowledgeable research team. It is the responsibility of the research organization to ensure that policies and SOPs are written and updated for study conduct and participant protection.
|
From page 153... ...
The Research ERB could assign a risk category to each study reviewed, and this assessment would provide oversight guidance for the program. Studies classified as "high-risk" would require more intensive and frequent monitoring of data and compliance with human participant protections.
|
From page 154... ...
DATA AND SAFETY MONITORING BY AN INDEPENDENT BODY Recommendation 5.6: All studies involving serious risks to participants, enrolling participants with life-threatening illnesses, or employing advanced experimental technologies (e.g., gene transfer) should
|
From page 155... ...
12It is also noted that further guidance regarding expectations, oversight, and funding for data and safety monitoring plans is needed from the relevant agencies.
|
From page 156... ...
Recent Guidance from the Food and Drug Administration In November 2001, FDA issued draft guidance entitled "Guidance for Clinical Trial Sponsors: On the Establishment of Clinical Trial Data Monitoring Committees" (2001a)
|
From page 157... ...
In addition, individuals who have completed a study or who have chosen not to continue their participation should also continue to be informed of any new findings, particularly new toxicology data from animal studies or serious adverse events that could have an effect on a participant's current or future the appropriate oversight and monitoring of the conduct of clinical trials to ensure safety of participants and the validity and integrity of the data for all NIH-supported or conducted clinical trials" (NIH, 1998)
|
From page 158... ...
Sponsor Communication with Regulatory Agencies, Investigators, Monitors, and Data and Safety Monitoring Boards/Data Monitoring Committees The regulations for FDA-regulated products during IND development studies detail specific sponsor reporting requirements to the agency.16 These include periodic progress and annual IND and Investigational Device Exemption (IDE) reports of safety data and protocol amendments.
|
From page 159... ...
DATA SECURITY: PROTECTING CONFIDENTIALITY All research with identifiable research participants involves issues related to the protection of confidentiality and privacy. lust as the protection program should monitor studies to ensure that risks are minimized and participant safety is assured, it also should take precautions to protect the privacy and confidentiality of participants during and after the study.
|
From page 160... ...
Research organizations and Research ERBs need to review their policies regarding exempt review in light of these regulations because they will affect organizational practices concerning the waiver of the requirement for informed consent and the need for ethics review. The regulations codify privacy standards throughout the United States and will have an effect on medical and behavioral research (see Chapter 7~.
|
From page 161... ...
Federal agencies also need to standardize their adverse event definitions and reporting requirements so that these reports can be more effectively used by Research ERBs to ensure participant safety. To protect research participants as fully as possible, it is essential that the relevant program mechanisms communicate with one another effectively.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.