The NIH Pragmatic Trials Collaboratory this week published a new chapter in its Living Textbook of Pragmatic Clinical Trials. Part of the Living Textbook’s new Ethics and Regulatory collection, the chapter discusses the logistics of using a single IRB (sIRB).
In 2016, the NIH issued a policy establishing the expectation that a “single IRB of record” will be used for all NIH-funded, multisite, human subjects research. The 2017 revision of the Common Rule likewise sets out a requirement for sIRB review of cooperative research.
The new chapter on sIRBs in the Living Textbook covers:
Joseph Ali, JD Assistant Professor, Dept. of International Health
Johns Hopkins Bloomberg School of Public Health
Core Faculty & Associate Director for Global Programs
Johns Hopkins Berman Institute of Bioethics
Tanya Matthews, PhD
HRPP Director
Kaiser Permanente Washington
Leslie J. Crofford, MD
Wilson Family Chair in Medicine
Professor of Medicine and Pathology, Microbiology & Immunology
Chief, Division of Rheumatology
Vanderbilt University Medical Center
Keywords
Ethics, IRB, FM-TIPS
Key Points
Trials are getting larger and collecting greater volumes of clinical data than ever before, often as part of Common Data Elements (CDEs). These data increasingly include info that might signal physical, mental health or behavioral health risks to patient-subjects (e.g. substance use, depression, anxiety, suicidality). This raises a lot of questions: Whose responsibility is it to monitor those risk factors? What should be monitored and how? Who can and should act/respond? What do patients and other stakeholders desire?
There are additional complexities with pragmatic clinical trials (PCTs), including overlapping roles and responsibilities of clinical and research staff; collection of broad sets of CDEs can make data monitoring more challenging; various and combined methods for data collection (e.g. extraction from health records and/or have treating clinicians or patients complete measures); and trials may operate under waivers of consent. There is a possible for risk-signaling data to “slip between the cracks.”
When trials collect risk-signaling data related to study outcomes, researchers and other stakeholders should understand and align stakeholder expectations; consider characteristics of the trial and study population to inform response; define triggers, thresholds, and responsibilities for action; identify appropriate response mechanisms and capabilities; integrate responses with clinical practices and systems; and address privacy demands. No single factor is more important than another.
Case Study: The Fibromyalgia Tens In Physical Therapy (FM-TIPS) trial was designed to demonstrate the feasibility of adding TENS to treatment of patients with FM in a real-world PT practice setting and determine if addition of TENS to standard PT for FM reduces pain, increases adherence to PT and allows patients with FM to reach their specific functional goals with less drug use.
FM-TIPS prospectively defined possible ethical concerns for the trial including concerns around mental health and substance use disorders, that led the study team to add language to the consent document about unexpected findings and the team decided to conduct monthly monitoring of data to identify any signals but to otherwise rely on clinicians to manage issues as is standard in PT practice.
Due to the low referral rates of fibromyalgia patents to PT (~30%), FM-TIPS had an emergent ethic issue related to patient recruitment and whether the study team could include the American College of Rheumatology criteria to screening to increase eligibility. In the end, the study team determined that making a new diagnosis unknown to the participant was beyond the scope of a PCT in a PT setting.
-Does it matter if the trial is being done at an integrated delivery system and a more traditional? There is a different level of decision making between the two cases Leslie described in the FM-TIPs trial. Setting is king when you are making some of these decisions; some settings are more academic and are used to these trials. Others are not used to doing trials. The setting really does matter, and it is a different way of thinking about the research enterprise.
–Actionable to whom by whom is a good question. Another way to think about this topic is when should or should not a trial take on a clinical role? In the FM-TIPS example, there was one case where the data collected by the trial team would also be collected by the clinical team. The timeliness of the response is also important; if the trial is monitoring something they need to be able to respond timely. In the second example, they were not able to. The context of the trial matters a lot in addition to actionability.
The compilation includes direct links to many of the laws, regulations, and guidelines, and serves as a resource for researchers, institutional review boards (IRBs), research sponsors, and others involved in human subjects research worldwide.
The 2015 edition includes hundreds of updates, including the addition of six new countries (Ghana, Guinea, Liberia, Malaysia, Saudi Arabia, and Sierra Leone).
Access the 2015 compilation here
Content is organized in the following topics:
1. General
2. Drugs and Devices
3. Research Injury
4. Privacy/Data Protection
5. Human Biological Materials
6. Genetic
7. Embryos, Stem Cells, and Cloning
The NIH Pragmatic Trials Collaboratory this week published a new chapter in its Living Textbook of Pragmatic Clinical Trials. Part of the Living Textbook’s new Ethics and Regulatory collection, the chapter discusses the logistics of using a single IRB (sIRB).