Clinical Researcher—December 2018 (Volume 32, Issue 10)
IRBs IN FOCUS
Lindsay McNair, MD, MPH, MSB; David Forster, JD, MA, CIP
This year marks the 50th anniversary of the founding of Western Institutional Review Board (WIRB), the first established independent ethical review board in the United States. WIRB’s parent company, WIRB-Copernicus Group, has spent this year looking back at the last five decades, in recognition of what a remarkable achievement 50 years of human subjects protection really is. An important aspect of this commemoration—and an especially rewarding one for us—was to explore the origins of WIRB, and the woman who made it all happen.
Angela Bowen was born on a farm near Taylorsville, Miss. in 1932, and decided to become a physician early in life, at a time when only about 7% of physicians were female. After graduating from high school at 16, she worked as a nurses’ aide to save money to put herself through medical school. In 1951, when she first began attending Mississippi State University (125 miles from Taylorsville), it was the farthest she had ever been from home.
She graduated from the University of Washington School of Medicine in Seattle, Wash. in 1963, one of only four women in a graduating class of 81 students. After graduation, Dr. Bowen completed her medical training and a fellowship in endocrinology in Seattle. She was awarded funding from the National Institutes of Health (NIH) to support her research on diabetes at the Virginia Mason Medical Center in Seattle.
Nurturing the Seeds of an IRB
Dr. Bowen and her husband owned farmland in Olympia, Wash., a town about 40 miles southwest of Seattle. One of Dr. Bowen’s patients was Robert Schmidt, owner of the Olympia Brewing Company. In 1967, Mr. Schmidt asked Dr. Bowen to consider moving her medical practice from Seattle to Olympia, to increase the number of local medical providers for the Olympia community. However, moving into private practice would have meant giving up the research grants from the NIH, since the grants had to be awarded to an institution rather than to an individual.
Mr. Schmidt had a solution; he suggested that the Olympia Tumwater Foundation, the nonprofit that was founded by the Brewing Company, could act as the recipient institution for her NIH grants. In December 1967, the foundation’s board agreed. However, the foundation wasn’t experienced in overseeing medical research, and wanted to make sure that appropriate protections were in place both for the foundation and the research. Before agreeing to take receipt of the grants, the foundation required that Dr. Bowen establish a committee of local physicians to review her research, and that the committee had to find the research conduct ethical and acceptable.
In 1968, this research oversight committee was established. Meeting monthly in Dr. Bowen’s office over lunch, the committee members discussed the ongoing conduct of the clinical research studies being conducted under the NIH grants and provided research oversight for Dr. Bowen and soon, for other local physicians as well. Notably, the committee was formed six years before there were any regulations requiring the independent review of clinical research.
Crises and Response
The 1960s marked a critical period in research ethics. In 1962, the U.S. Food and Drug Administration (FDA) regulations for drug approval were greatly strengthened in response to the discovery that thalidomide was causing birth defects. FDA was given the power to approve a drug for marketing only if it was satisfied with the data demonstrating both the drug’s safety and efficacy.
Among the era’s cases of unethical research, in 1963, it was revealed that researchers at the Jewish Chronic Disease Hospital were injecting patients with live cancer cells to see if they would develop cancer, without consent of the patients. From 1956 to 1972, doctors at the Willowbrook State School for the Retarded in New York were injecting children with hepatitis so they could research treatments. Although consent was technically obtained from the children’s parents, admission to the overcrowded school was likely dependent on agreeing to allow the injections, with parents also told that infection was inevitable in the school setting in any case.
Most significant and impactful on research oversight was the publication on the conduct of the “Tuskegee Study of Untreated Syphilis in the Negro Male.” Started in 1932, the year Dr. Bowen was born and only 250 miles from her hometown, this Public Health Service study began as an effort to document the outcomes of untreated syphilis to support requests for funding treatments, although the available therapies were largely toxic and ineffective. The study continued for 41 years, despite the subsequent widespread availability of effective antibiotic therapies, which were withheld from study participants, with the continuing support of both the Public Health Service and medical organizations. In 1973, a reporter became aware of the study and wrote about it in the in the New York Times, bringing it to the attention of the public and Congress.
These incidents, among others, finally led to Congressional action. Congress passed the National Research Act of 1974. These issues also drove the Department of Health, Education, and Welfare (now the Department of Health and Human Services [HHS]) to adopt the first regulations for the protection of human subjects in research in the same year. These regulations required institutions to form a committee—an institutional review board (IRB)—to review and approve all research proposals before they were submitted for federal funding requests. Adopting this new terminology, Dr. Bowen incorporated her research oversight committee as the Western Institutional Review Board (Western IRB, or WIRB) in 1974.
Since these new regulations were part of the federal research funding process, they did not apply to research that was privately funded (such as by pharmaceutical companies) or conducted under the oversight of agencies such as the FDA. The National Research Act also led to the creation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The National Commission wrote a series of carefully deliberated reports on the ethical conduct of research, culminating in the Belmont Report in 1979.
In 1981, as a result of the National Commission recommendations, HHS modified its regulations. For the first time, the FDA adopted regulations requiring IRB review of FDA-regulated clinical research, whether it happened in an institution or in a private doctor’s office.
Many hospitals conducting research had already established IRBs for federally funded projects which could absorb the additional review of FDA-regulated research. However, anyone practicing medicine and doing research in private practice, or at an institution that didn’t already have an IRB in place, needed to find an IRB to review their work.
By that time, Dr. Bowen and WIRB were well-known to the FDA and to many pharmaceutical companies with which she or the other Olympia physicians had worked. Dr. Bowen had established a reputation as an ethical researcher, with an IRB that already had 13 years of research review experience. During the next several years, WIRB grew rapidly as it became the primary IRB for FDA-regulated research conducted in physicians’ practices and clinics. WIRB was the original model of a “central IRB” in the United States.
A Continuing Legacy
In subsequent years, WIRB has been prominent in many landmark events shaping the clinical research oversight and regulatory structure of the United States. For example, when regulatory lapses caused the shutdown of local IRBs at some major academic research centers in the late 1990s, Dr. Bowen and WIRB were asked to step in and provide the necessary research oversight to allow critical research studies to continue until the local IRBs could become compliant and be reopened.
Support of research institutions grew rapidly. WIRB now has formal agreements to act as the reviewing IRB for more than 2,700 institutions and academic medical centers. From those lunchtime meetings in Dr. Bowen’s office in Olympia, WIRB has grown into an organization that now reviews almost 3,000 new protocols each year, with oversight of more than 30,000 investigators.
WIRB’s central IRB structure also foreshadowed the significant changes in IRB oversight for all clinical research in the United States. In January 2018, the NIH implemented a policy mandating that all multicenter studies under NIH grants be overseen by a central, single IRB rather than multiple local IRBs. The revised Common Rule, which is currently expected to become effective in January 2019, also includes a single IRB requirement for multicenter research. The IRB system in the United States has steadily evolved during the past four decades to look more and more like Dr. Bowen’s original model of IRB oversight.
After retiring from WIRB in 2012, Dr. Bowen passed away at her home in Olympia in 2017. The organization she founded continues, celebrating its 50th anniversary this year. It is a privilege for all those at WIRB to be part of an organization which had played such a remarkable role in the facilitation of scientifically rigorous and ethically conducted clinical research during the last half-century.
Several of Dr. Bowen’s former colleagues share their memories of her compassion and determination in a video at https://wcgclinical.wistia.com/medias/evwue1d2uz.
To learn more about the history of WIRB, visit https://www.wcgirb.com/50.
Lindsay McNair, MD, MPH, MSB, is chief medical officer at WCG (WIRB-Copernicus Group).
David Forster, JD, MA, CIP, is chief compliance officer at WCG (WIRB-Copernicus Group).