The Office for Human Research Protections (OHRP) has posted a series of six webinars explaining the recent Notice of Proposed Rulemaking (NPRM) regarding revisions to the Common Rule (the federal policy for human subjects protection). The presentations by policy experts can be viewed anytime; they cover the following topics:
- Overview of the NPRM
- Exclusions and exemptions
- Informed consent
- IRB review and operations
- Research with biospecimens
- Secondary research use of data
For more information on the NPRM, visit the OHRP website. The deadline for comments on the proposed revision has been extended to January 6, 2016.
A new series of 12 articles published in a special issue of the journal Clinical Trials addresses ethical and regulatory challenges particular to pragmatic clinical research. Pragmatic clinical trials are designed to efficiently provide answers to important clinical questions, yet they present special challenges in conforming to the ethical and regulatory guidelines that were developed for more traditional clinical research. The special issue describes these challenges and begins to outline possible solutions that will protect the rights and welfare of research participants while allowing pragmatic clinical trials to gather much-needed evidence for informing healthcare decisions. An introductory article is followed by 11 articles addressing individual topics, such as alteration of informed consent, privacy, gatekeepers, and defining minimal risk research. The effort was funded by the NIH Health Care Systems Research Collaboratory, with additional support from the Patient-Centered Outcomes Research Institute (PCORI), and involved diverse groups of stakeholders, including researchers, patient advocates, bioethicists, and regulatory experts. Robert M. Califf, MD, and Jeremy Sugarman, MD, MPH, were editors of the special issue.
For more information:
In a forthcoming article in Healthcare, Dr. Eric Larson and colleagues present practical advice based on case studies from the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. Physician–scientists, health services researchers, and delivery system leaders provide insight from their experience launching a pragmatic clinical trial (PCT) as part of the Collaboratory.
The authors make 5 recommendations:
- Establish a partnership from the get-go
- Do a pilot project
- Take advantage of existing hospital and health system infrastructure
- Minimize the impact on clinical workflow
- Remember that even high-priority research questions must be balanced with the systems’ greatest priority: providing good healthcare to patients.
The authors note that researchers need to be flexible and prepared to adjust the study design to the workflow and culture of the system.
Reference: Larson E, Tachibana C, Thompson E, et al. Trials without tribulations: Minimizing the burden of pragmatic research on healthcare systems. Healthcare. 2015; in press. doi:10.1016/j.hjdsi.2015.07.005
Watch Dr. Larson’s Grand Rounds Presentation from June 2013: Trials, Not Tribulations: Minimizing the Burden of Research on Health Care Systems
In a commentary published this week in Modern Healthcare, Eric Larson, MD, MPH, and Karin Johnson, PhD, of Group Health Research Institute, argue that greater collaboration is needed between clinical researchers and healthcare system executives to address a “a gap between research approaches and delivery system needs.” Perspectives gathered through a survey and Institute of Medicine workshop with healthcare executives indicated that research is not conducted fast enough or designed in a way that facilitates translation of evidence into clinical practice. The NIH Collaboratory and National Patient-Centered Clinical Research Network (PCORnet) are cited as examples of effective partnerships between researchers and healthcare leaders; these research programs are addressing high-priority clinical questions and generating actionable knowledge. According to Drs. Larson and Johnson, pragmatic clinical trials and big data offer opportunities to create a learning health system, but this will require combining the perspectives and expertise of researchers and stakeholders from healthcare delivery systems. Drs. Larson and Johnson are part of the NIH Collaboratory’s Health Care Systems Interactions Core, a working group that “aims to support and facilitate productive collaboration between researchers, clinicians, and health system leaders.”
In a study recently published in JAMA Oncology, researchers found that patient reporting of adverse events of cancer treatment using a new scale gave valid and reliable assessments that correlated with standard measures of functioning and quality of life. The National Cancer Institute (NCI) developed a patient-reported outcome (PRO) version of its Common Terminology Criteria for Adverse Events (CTCAE), which is the standard system for reporting toxicities of cancer treatment in clinical trials. The PRO-CTCAE was then tested among more than 900 patients undergoing treatment at 9 cancer centers. As described in a commentary by Benjamin Movsas, MD, these results are encouraging for PROs to be integrated in informing treatment recommendations, symptom management, and even labeling decisions.
Read more about PROs in the Living Textbook chapter on this topic.
A new article published this week in JAMA describes the cluster randomized trial design. The article is part of JAMA’s Guide to Statistics and Methods series, which publishes explanations of analytic and methodologic approaches used in current research articles to help clinicians better understand the research.
In “Cluster Randomized Trials: Evaluating Treatments Applied to Groups,” Drs. William J. Meurer and Roger J. Lewis define cluster randomization, describe its advantages and limitations, and provide guidance on interpreting cluster randomized trials. The article discusses aspects of a recent cluster randomized trial, the RESTORE trial, as an example.
In RESTORE, pediatric intensive care units were randomized to assess the effects of a nurse-implemented sedation protocol for children with acute respiratory failure on mechanical ventilation. As Meurer and Lewis point out, “interventions that involve training multidisciplinary health care teams are practically difficult to conduct using individual-level randomization, as health care practitioners cannot easily unlearn a new way of taking care of patients.” Cluster randomized designs are therefore often used for this type of research, and it is important for clinicians to be able to understand and evaluate these studies.
Meurer WJ, Lewis RJ. Cluster randomized trials: evaluating treatments applied to groups. JAMA. 2015;313:2068-2069. PMID: 26010636. doi:10.1001/jama.2015.5199.
The Clinical Trials Transformation Initiative (CTTI) has released new recommendations encouraging adoption of a central institutional review board (IRB) model for multicenter clinical trials. The recommendations are based on results from its Central IRB Advancement Project. Along with the recommendations, CTTI offers tools, including evaluation checklists and an IRB authorization agreement template, to help organizations implement a central IRB model.
Read the complete announcement on the CTTI blog.
A new feature on the FDA.gov website allows you to search for FDA guidance documents on all topics from one convenient location:
FDA Guidance Document Search Feature
Guidance documents represent the FDA’s current thinking on particular topics and are used by stakeholders to understand the agency’s interpretation of regulations and policies.
There are approximately 3,000 guidance documents available on the site, which can be searched by keyword or filtered by date issued, FDA organizational unit, subject, draft or final status, and comment period.
The search feature was implemented in January 2015 in response to site visitor feedback.
The 2015 edition of the International Compilation of Human Research Standards is now available. Compiled by the U.S. Department of Health and Human Service’s Office for Human Research Protections, the document indexes more than 1,000 laws, regulations, and guidelines governing human subjects research in over 100 countries.
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:
2. Drugs and Devices
3. Research Injury
4. Privacy/Data Protection
5. Human Biological Materials
7. Embryos, Stem Cells, and Cloning
This month’s issue of the Journal of General Internal Medicine features a systematic review of stakeholder engagement in comparative effectiveness research and patient-centered outcomes research. Thomas W. Concannon, PhD, and coauthors identified 70 peer-reviewed articles since 2003 that reported on this topic.
Key results included:
- Patients were the most commonly engaged group, followed by modest engagement of clinicians, and infrequent engagement of other stakeholders across the healthcare system.
- Stakeholders were more often engaged in earlier stages of research (evidence prioritization and generation) than in later activities such as evidence interpretation and application.
Overall, reporting of stakeholder activities and the effects of engagement were highly variable in the literature. To address this, the authors developed a 7-item questionnaire for the reporting of stakeholder engagement in research. A suggested plan for future research on stakeholder engagement is also outlined.