The Johns Hopkins Gazette: September 4, 2001
September 4, 2001
VOL. 31, NO. 1


External Review Committee Submits Report

Hopkins releases findings and addendum to the public and OHRP

Johns Hopkins Gazette Online Edition

The external review committee appointed by university President William R. Brody to help evaluate Hopkins' research policies and procedures has submitted a report with some substantial criticisms of research oversight at the institution, along with an addendum that affirms the corrective action plan advanced by Hopkins following the tragic death of a research volunteer.

"Oversight of clinical research at Johns Hopkins must be significantly strengthened," the report said, while also endorsing in its addendum actions Hopkins already has taken or planned. In addition, the document encouraged further "collaborative behavior" between research institutions and the federal agencies involved in funding and oversight.

"We are pleased with the corrective action plan submitted to the OHRP [Office for Human Research Protections] and their acceptance of it," the report addendum stated, adding that "the external review committee is confident that these actions will correct and improve clinical research at Johns Hopkins as well as provide a model for other academic medical centers." It further commended Hopkins for its rapid embrace of corrective actions, reflecting "commitment to the highest level of protection of human subjects of clinical research."

The main report, rigorous in its sometimes unsparing language, essentially echoed the criticisms already made in the Hopkins internal review committee report on July 16 and in findings by the OHRP. That is, it focused on procedures and organization of Hopkins' institutional review boards, the content of consent forms, Food and Drug Administration requirements, the role of regulatory agencies in general and oversight policies needed especially to ensure the safety of volunteers in studies with no therapeutic potential.

Describing what it termed defects and inadequacies in the asthma study review process, literature search used to support the research, the consent form signed by volunteers, record keeping and the preparation of the chemical used in the asthma research, the committee report called on Hopkins to both tighten research study oversight and lead efforts to "collegially develop appropriate standards" for the use of nonapproved drugs in human studies.

The five-person committee, convened by Brody in July and chaired by physician Samuel Hellman, A.N. Pritzker Distinguished Service Professor at the University of Chicago, was asked both to review the facts and circumstances surrounding the death of a healthy volunteer, Ellen Roche, after her participation in a Hopkins asthma research study and to recommend any alterations to policies that would reduce the likelihood of such an event in the future.

While critical of some practices and policies at Hopkins, the report also noted that "some of the issues that we identified apply to all" academic medical centers.

"I am grateful to Dr. Hellman and the members of the external review committee, as well as to its predecessor, our internal review committee, for the extraordinary time and effort that have gone into these careful evaluations and recommendations," Brody said. "These reports, together with suggestions by OHRP and the FDA, offer valuable guides for improving our institutional processes.

"At Johns Hopkins," Brody added, "we have taken immense pride in our scientists and in their ability consistently to produce the highest level of peer-reviewed, government-funded research. The results of their work have contributed to life-saving advances against disease and disability. Now there is a consensus that significant growth in the volume of research must be matched by growth in infrastructure allocated to oversight of such research. We are pledged to do that.

"Our first goal, always, " Brody said, "is to protect our patients and volunteers. Ellen Roche's death was a tragedy, and we grieve for her family, but one way we can redeem the tragedy is to seize the opportunity to strengthen and improve our commitment to safety."

The Hellman committee report and its addendum, already sent to OHRP; a list of the committee's members; and a summary of corrective actions taken or planned by the university can be found at

Actions Taken to Strengthen Research Oversight at Hopkins

On Aug. 29, Johns Hopkins Medicine released the following statement:

Research conducted at Johns Hopkins produces life-saving and life-enhancing discoveries. To ensure the safety of those who participate in this research, Johns Hopkins is putting in place significant new safeguards that have been endorsed by the federal government and an external review committee. These safeguards include:

Expanding the number of institutional review boards charged with research oversight. Hopkins has added three IRBs, increasing the total used for the re-review process to six, and pledged at least four permanent IRBs.

Intensifying training for all IRB members, in cooperation with the Office for Human Research Protections. Six hours of on-site OHRP instruction have taken place for IRB members and staff. The sessions were videotaped for viewing by future staff and IRB members.

Supplementing Web-based instruction for faculty and staff on use of humans in research by presenting at Hopkins the nationally acclaimed PRIMIR course IRB 101.

Requiring prior academic review of research protocols before they are submitted to IRBs. This review will include examination of scientific worth, validity of study design and safety.

Implementing the full convened IRB meeting review process to ensure full IRB review, discussion and documentation of each protocol.

Working with OHRP to develop an approved checklist to guide re-review of protocols, as well as discussion of new and renewal protocol review.

Establishing a committee chaired by Ruth Faden, executive director of the Johns Hopkins Bioethics Institute and a national authority on the ethics of human participation in research, to review and revise policies for participation of employees and students as normal volunteers in research.

Taking steps to ensure timely, written documentation of IRB deliberations.

Designating a staff member as consent form reviewer to aid investigators in developing consent forms that provide all necessary information regarding the purpose, risks and benefits of the research.

Requiring investigators to collaborate with a librarian and a pharmacist to strengthen literature searches regarding previous studies for any substances for which the FDA does not require an IND. The goal of the collaboration is for both the librarian and pharmacist to help search appropriate databases for potential side effects.

Establishing a policy of querying the FDA in all instances when a nonapproved substance is specified in a protocol to determine if an IND is required. If the FDA does not require an IND, the investigator must provide sufficient evidence that the substance in question is safe for human use, including safety data generated by an outside organization, when pertinent, regarding animal studies, purity of the substance and whether the material meets requirements for human use.

Reminding all Hopkins faculty of institutional policies regarding IRB notification of changes in protocols and adverse events.

To further ensure sufficient oversight of studies that administer drugs or other substances into humans in research studies, initiating policies requiring wider use of the Investigational Drug Service by faculty based at both Hopkins Hospital and the Johns Hopkins Bayview Medical Center. The new policy requires that a pharmacist be involved in the preparation of any materials to be used in humans in such studies.

Increasing random quality-control checks of ongoing research protocols to ensure safety and adherence to best practices.

Beyond these specific actions, Johns Hopkins recognizes the need for a broad and long-term educational effort, at all levels of the institution, to ensure a full appreciation of the ethical obligations inherent in research involving humans. This broader effort will be pursued aggressively in the coming academic year.

In the wake of the tragedy of the death of a healthy volunteer in a Hopkins research study, we are fully engaged in improving our processes and strengthening our safeguards to reduce the chance of such an event occurring again. We are very proud of the Hopkins research that has done so much to improve health and extend life here in the United States and around the world. As we raise the bar on research safety, we believe these changes will enhance our research efforts.