Mark Barnes

Preparing for Responsible Sharing of Clinical Trial Data

The authors review the potential benefits and unintended consequences of the broad sharing of participant-level data from clinical trials. Several options for governance structures that could be implemented to provide expanded access to clinical trial data are discussed.

A Global, Neutral Platform for Sharing Trial Data

Brigham and Womens Hospital–Harvard Universitys Multi-Regional Clinical Trials Center, along with partners, is designing a platform to link existing data-sharing platforms and communities and host data from investigators who want to share data but lack the resources to do so.

Financial Conflicts of Interest in Human Subjects Research: The Problem of Institutional Conflicts

n both academic literature and the media, financial conflicts of interest in human subjects research have I come center-stage. The cover of a recent edition of Erne magazine features a research subject in a cage with the caption “human guinea pigs,”’ signifying perhaps that human research subjects are no more protected from research abuses than are laboratory animals.* That magazine issue highlights three well-publicized cases of human subjects research violations that occurred at the University of Oklahoma, the University of Pennsylvania, and Johns Hopkins University. At St. John Medical Center in Tulsa, Oklahoma, a study that was co-sponsored by the University of Oklahoma Health Sciences Center investigated an experimental vaccine for malignant melanoma. In that case, the chair of the university’s institutional review board (IRB) the committee within each medical institution charged with ethics review of human research projects undertaken at that institution -and the dean of the University’s College of Medicine allegedly concealed from both the IRB and the United States Food and Drug Administration (FDA) a report by an outside consulting firm that had found severe deficiencies with the melanoma vaccine study being conducted at the medical center. The outside consulting firm had been engaged by the IRB chair and dean of medicine after the research nurse of the investigator3 in charge of the study reported to them substantial variations from the research protocol, such as improper storage of the melanoma vaccine, inadequate recordkeeping, and failure to report adverse side-effects to the IRB. In response to the outside report, the IRB chair and dean of medicine halted the trial, but the IRB chair stated in an annual report that there were no significant safety issues related to the melanoma vaccine. A letter was sent to all trial participants

Revised ‘Common Rule’ Shapes Protections For Research Participants

Investigators and institutions have begun to prepare for new federal protections of study participants set to take effect in 2018.

Protecting Research Participants While Reducing Regulatory Burdens

THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (HHS) has proposed sweeping revisions to the federal regulations for the protection of human research participants. The goal is to “enhance protection while simultaneously eliminating unreasonable burdens.” Although the goal is admirable, some changes intended to remove unnecessary regulatory burdens may allow serious risks (ie, the probability of harm is significant, not merely possible or conceivable), particularly to highly vulnerable participants (ie, participants’ ability to give free and informed consent is seriously compromised). In this Commentary, 3 major issues in the Advance Notice of Proposed Rule-Making (ANPRM)—ensuring riskbased protections, institutional review board (IRB) reviews of multisite studies, and informed consent—are discussed. New policies to reduce regulatory burdens should be coupled with procedures to protect participants if research poses serious risks, involve highly stigmatizing conditions, or include significantly vulnerable participants.

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees

A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Womens Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval.

Responsibilities of Data Monitoring Committees Consensus Recommendations

Background: A data monitoring committee (DMC) has special responsibilities for protecting the safety of clinical trial participants. Few guidance documents are available that address the operations and mechanics of establishing, serving on, or reporting to a DMC. This article provides a practical guide to sponsors, institutions, and individuals responsible for, or serving on, a DMC. Methods: A workgroup of professionals from academia and not-for-profit and commercial organizations that included investigators, statisticians, patient advocates, and ethicists met to define the essential elements of planning, coordinating, and populating a DMC. All members of the group have formed, served on, advised, or worked with DMCs. Results: The group outlined the objectives and mechanics of running a DMC, including operational and practical considerations, membership characteristics, roles, members’ liability, and indemnification. Further, it delineated the roles and responsibilities of each DMC member. Conclusions: The group recommended practices for each phase of the DMC process from inception through execution of a clinical trial, with appropriate considerations for confidentiality. The group’s practical guidance should assist in comprehensive oversight of appropriate clinical trials and should help DMC members execute their obligations with greater assurance.

Federal Research Regulations for the 21st Century

The proposed changes to regulations for human-subjects research fail to anticipate that ongoing innovations will necessitate future changes, and they fail to build on available empirical evidence and current technology to improve protections for research participants.

Chevron v Echazabal: Public Health Issues Raised by the “Threat-to-Self” Defense to Adverse Employment Actions

In June of 2002, the US Supreme Court upheld a regulation that allows employers, under the Americans with Disabilities Act, to make disability-related employment decisions based on risks to an employees own personal health or safety. Previous judicial decisions had allowed employers to make employment decisions based on the threat that a workers medical condition posed to others but had not addressed the issue of risk posed to an employees health by his or her own disability. The authors comment on the potential effects of the courts decision for occupational health practitioners charged with assessing the degree of risk and harm of a particular workplace environment and for public health efforts aimed at curbing workplace injury and sickness.

Research Misconduct Involving Noncompliance in Human Subjects Research Supported by the Public Health Service: Reconciling Separate Regulatory Systems

Over the past three decades, two separate federal regulatory structures have emerged, each seeking to assure separate aspects of the integrity and ethics of research conducted using federal funding. One set of regulations is described in the Public Health Service Policies on Research Misconduct and relates to research misconduct, defined as consisting of fabrication of data or results, falsification of data and results, or plagiarism, in accordance with the federal-wide definition adopted by the Office of Science and Technology Policy. The second set of regulations, set forth in the Department of Health and Human Services regulations on the protection of human subjects (known as the “Common Rule”), prescribes a set of ethical and procedural protections for research involving human subjects. These two sets of research regulations are distinguished from each other by having different foci of enforcement, priorities of protection, oversight officials, oversight procedures, seizure of evidence, standards of proof, expectations of privacy, and appeal procedures for researchers who are subject to adverse findings and penalties. These differences are significant and fundamental. They complicate the process of compliance for institutions and researchers, who are expected to adhere to both sets of standards for the same federally funded research activities in research with human subjects. Compliance is especially complicated when suspected violations of both sets of standards must be investigated and resolved concurrently. This document represents an effort to provide institutions and individuals with practical suggestions as they try to comply with both sets of regulations.