September 4, 2001|
VOL. 31, NO. 1
External Review Committee Submits Report
Hopkins releases findings and addendum to the public
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
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
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.
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
Web-based instruction for faculty and staff on use of humans
in research by presenting at Hopkins the nationally
acclaimed PRIMIR course IRB 101.
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.
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
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
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
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.
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
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.
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