PRINCETON, N.J.—March saw the publication of an Ethics Tool Kit in the Journal of Medical Ethics (JME) for clinical trial protocols, a co-written effort by 20 clinical research experts, including Dr. Lindsay McNair and David Forster, chief medical officer/president of consulting services and chief compliance officer, respectively, for WIRB-Copernicus Group (WCG). The toolkit was developed by the Multi-Regional Clinical Trials (MRCT) Center of Harvard and Brigham and Women’s Hospital working group. The experts for this effort, according to the JME article, included members of “academic institutions (6), pharmaceutical companies (4), non-profit organizations (4), law firms (3) and ethics committees (3), with backgrounds in clinical trials, medicine, bioethics and law.”
The MRCT paper, “Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees,” details “11 Essential Elements” that should be considered for a dedicated ethics section in a clinical research protocol. The 11 Essential Elements of the kit cover the following topics: addressing a relevant question, choice of control and standard of care, choice of study design, choice of subject population, potential benefits and harms, informed consent, community engagement, return of research results and incidental findings, post-trial access, payment for participation and study-related injury.
“We recommend including a dedicated ethics section in every protocol, because it will help ethics teams to proactively articulate ethical considerations associated with the protocol. That step should improve the dialog between ethics committees and clinical research teams, and among the research team members themselves,” McNair remarked in a news release.
Forster added that such discussions “will enhance consistency and transparency between clinical trial protocols and ethical committee reviews, and may in turn expedite the review process by anticipating the concerns of those reviewers.”
The MRCT Center team assessed 100 clinical trial protocols that had been reviewed and approved by ethics committees to see if the Essential Elements were included and discussed from an ethics perspective. All the selected protocols were from multicenter intervention trials (medical, social/behavioral or device) in which at least one site was outside of the United States. All protocols involved greater than minimal risk, and informed consent forms, if available, were also reviewed.
The team found that the first Essential Element, addressing a relevant question, was included in 96 percent of protocols. Other criteria appeared far less often; community engagement and post-trial access were featured in only 9 percent and 22 percent of protocols, respectively. Potential benefits and harms were not properly discussed in 24 percent of protocols, while challenges in informed consent were lacked discussion in 44 percent of protocols.
The JME paper makes a point to note that “no regulation presently requires explicit discussion of ethical issues in written clinical trial protocols or informed consent forms.” While it admits the sample size was limited and cautions that the findings should not be “overinterpreted,” it also says that “Nonetheless, these findings suggest that critical ethical issues typically of serious concern to ethics committees are often not addressed explicitly in submitted clinical trial protocols.”
In collaboration with colleagues at the Global Health Network at Oxford University, the MRCT Center is also aiming to make this Ethics Tool Kit more accessible for researchers in low- and middle-income countries. In line with those efforts, the organizations have made an online course that teaches the Essential Elements via a series of 11 modules.
The MRCT Center is also furthering its work in clinical trial ethics with the launch of a new initiative, the Bioethics Collaborative, which was announced in March. According to the organization’s website, this initiative “is a forum to encourage the discussion of bioethical issues among stakeholders in global clinical trials for drug and device development. Our meetings will bring together scholars, executives and scientists from academia and industry to share, define, study and propose ethical frameworks for topics including human subject protections, biospecimens and research integrity. We will look at real-life settings as well as develop approaches to address emerging and unanticipated issues as the pace of research continues to accelerate. The Collaborative will be a neutral forum to provide ethical guidance on global clinical trials concerns.”