{"id":221,"date":"2019-11-08T15:40:24","date_gmt":"2019-11-08T15:40:24","guid":{"rendered":"https:\/\/www.socra.org\/blog\/?p=221"},"modified":"2019-11-27T16:25:38","modified_gmt":"2019-11-27T16:25:38","slug":"the-changing-landscape-of-human-subjects-research","status":"publish","type":"post","link":"https:\/\/www.socra.org\/blog\/the-changing-landscape-of-human-subjects-research\/","title":{"rendered":"The Changing Landscape of Human Subjects Research"},"content":{"rendered":"\n
\"\"<\/figure>\n\n\n\n

Amy Waltz, JD, CIP<\/strong>
Associate Director – Regulatory Affairs, Reliance, Outreach<\/strong>
Indiana University<\/strong> <\/p>\n\n\n\n

Abstract<\/em><\/strong>:<\/em> <\/em>Understanding context is key to understanding the\nregulations and complying with regulatory requirements. This article explores\nthe historical context and events that shaped the current human subjects\nprotection regulations and how changes in human subjects research and public\nperception have impacted the proposed revisions to the human subjects\nprotection regulations. The 2017 revisions to the Common Rule (45CFR46) and the\nimpact of these revisions on government funded research are also addressed.<\/em><\/p>\n\n\n\n\n\n\n\n

Introduction<\/strong><\/h2>\n\n\n\n

Research compliance is one of\nthe few areas within the United States regulatory system that demonstrates a\ndirect correlation between real-life events, public opinion, and changes in\nregulatory policy. In 2017, the Common Rule, the set of regulations that defines\nhuman subject protection in the United States, was revised for the first time\nin more than twenty-five years, beginning a new regulatory era in research\ncompliance. <\/p>\n\n\n\n

It is extremely important for\nthe research community to understand the context behind those regulations and\nthe recent changes. Understanding the historical context helps researchers and\ninstitutional review board (IRB) administrators appropriately balance potential\nadministrative burden with ensuring the highest ethical conduct of research. While\nthe Common Rule, and IRBs, are often seen by researchers as simple\nadministrative burden, they are based in a historical context rife with ethical\nviolations, even when the violators meant well. <\/p>\n\n\n\n

The research community is in\nan excellent position right now, being given the revised Common Rule and the regulatory\nflexibility that it provides, to use the past to define the future of research.\n<\/p>\n\n\n\n

Early examples of human subjects research<\/strong><\/h2>\n\n\n\n

Research in the early years\nof medical experimentation looked very different than it does today. Those who\nparticipated in research, unwittingly or not, were not categorized as \u201chuman\nsubjects\u201d and specifically protected. Today, the lines between research and\nclinical care are carefully drawn. Research and clinical care are explained\ndifferently to subjects, and logistics, such as billing, is handled separately\nin many cases. In the early days of medical experimentation, no formal\ndistinction between research and clinical care was made, and human subjects\nresearch was not considered a separate scientific discipline as it is today.\nInstead, research was simply conducted alongside clinical treatment.  <\/p>\n\n\n\n

For example, the great Sidney\nFarber created chemotherapy at Boston Children\u2019s Hospital. At that time, there\nwere no treatment options for pediatric cancer patients, who almost always succumbed\nto their disease. As those who work in rare and difficult diseases today can\nunderstand, serving as a treating provider for pediatric cancer patients, knowing\nthere was little to be done, was exceedingly difficult. Dr. Farber and his\ncolleagues developed chemical compounds to try to help children with leukemia.\nDr. Farber\u2019s work was methodical, ground breaking, and ultimately defined the\ntreatment of cancer; however, the informed consent document as we know it today\ndid not exist for Dr. Farber\u2019s experiments. <\/p>\n\n\n\n

Another example of early\nhuman subjects research has captured the interest of Americans in recent years.\nIn 1951, George Gey created the first immortal cell line from cells removed\nfrom an African-American woman named Henrietta Lacks, who had been diagnosed\nwith a violent form of cervical cancer. The cancer spread extremely rapidly and\nshe passed away within a few months of diagnosis. Dr. Gey was a researcher at Johns\nHopkins University who had been searching for an immortal cell line, or a group\nof cells that would grow for prolonged periods, which he hoped would allow bench\nscientists to conduct better research. He had asked colleagues at the University\nand affiliated hospitals to take an extra swab of cells from cancer patients\nfor testing by Dr. Gey. The cells taken from Henrietta Lacks were collected\nwith that request in mind, and no one thought to obtain consent. At that time,\nthe concept of informed consent for research as we know it simply did not exist\nyet.  <\/p>\n\n\n\n

Henrietta Lacks\u2019 immortal\ncells have changed the face of medical research. Her cells are used throughout\nthe medical and research world; however, neither Henrietta Lacks nor her family\nconsented to the original or ongoing use of her cells. The story became widely\nknown in 2010 when Rebecca Skloot published The\nImmortal Life of Henrietta Lacks,<\/em> which became a New York Times bestseller.\nThe book resulted in the first public acknowledgment of the contribution of the\nLacks\u2019 family to medical science and sparked a national public discussion about\nthe ethical use of biospecimens for research, including how biospecimens are\ncollected, and the information people should have when their biospecimens are\nused for medical research. Today, the Lacks family is involved in discussions\nof how some of Henrietta Lacks\u2019 cells are used. The book changed the way the research\nworld treated the Lacks family.  The\ndiscussion in the research community about biospecimens has changed the regulatory\nperspective on research requirements. <\/p>\n\n\n\n

The worst-case scenario<\/strong><\/h2>\n\n\n\n

These examples took place\nwell before research regulations existed. The first consideration of human\nsubjects as we know it today did not occur until after the global public\nlearned of Nazi experimentation during World War II. Before and during World\nWar II, the Nazis committed terrible atrocities in the name of medical science\nusing prisoners of war, Jews, and children. Nazi doctors conducted systematic investigations\ndesigned to test very specific hypotheses. Many of the experiments were focused\non the war effort and attempted to create a better soldier or lessen the\neffects of the body\u2019s reaction to cold, hunger, altitude, and pain. The\ninfamous Nazi doctor, Josef Mengele, conducted genetic research on more than 700\npairs of twins.<\/p>\n\n\n\n

The world did not hear about\nthese atrocities until the Allied forces entered Nazi Germany toward the end of\nthe war and found evidence of carefully-documented medical experimentation in\nconcentration camps and Nazi strongholds around Europe. After the war, hundreds\nof Nazis were tried for war crimes and crimes against humanity, including\nmedical experimentation, at the Nuremburg Trials. <\/p>\n\n\n\n

Like most legal trials, the\njudgments rendered at the Nuremberg Trials, and the rationale for those\njudgments, were documented in the judges\u2019 opinions about the cases. The Nuremberg\njudges who oversaw the medical experimentation cases thought carefully about the\nethics of medical research and how medical research should be conducted. They discussed\nit extensively in their opinions. The judges eventually wrote the first ethical\ndoctrine for conducting medical research, which became known as the Nuremburg\nCode. The document is often considered the basis for other ethical doctrines\nworld-wide.<\/p>\n\n\n\n

The worst-case scenario here at home<\/strong><\/h2>\n\n\n\n

After the Nuremberg Code, unethical research practices were a topic of global debate. Unfortunately, there were examples of ethical violations in medical research here in the United States as well. The Tuskegee syphilis studies brought ethical issues in research with human subjects to the forefront of the public eye. These studies were conducted from the 1930sthrough the 1970s, and they were funded by the United States Public Health Service. The Tuskegee syphilis studies were designed to study the natural progression of untreated syphilis over time. When the research began, syphilis was prevalent in African-American men, especially those in poverty, so study doctors focused on that population, offering recruitment incentives which would be especially attractive to the target participants: free medical care, meals, and burial insurance. Given the participants\u2019 need for these things, many now consider those incentives to be unduly influential. <\/p>\n\n\n\n

Undue influence was not the only ethical issue in the Tuskegee syphilis studies. Conduct of the study led to a lack of informed consent and failure to mitigate further risk to participants. For example, when the researchers began having trouble recruiting participants, they simply stopped telling potential subjects that they were studying syphilis. Many of the participants never knew that they had syphilis and were never told, despite participating in the syphilis studies for years. Furthermore, study doctors never offered participants a treatment for their disease, despite the fact that a viable treatment became available in the 1940s, while the studies were ongoing. <\/p>\n\n\n\n

It is difficult to imagine\nresearch being conducted in this way under the current regulatory environment. Subsequent\nregulatory oversight of human subjects research in the United States focused on\navoiding and mitigating the types of issues demonstrated by the Tuskegee\nsyphilis studies. <\/p>\n\n\n\n

Development of the regulations <\/strong><\/h2>\n\n\n\n

This historical context drove\nthe development of the regulations in the United States (Table 1). The major\nethical violations that occurred in the Tuskegee syphilis studies – coercion, lack\nof informed consent or understanding, failure to treat, and harming research participants,\nled regulators to directly address such issues in the Belmont Report and the\nsubsequent regulations. <\/p>\n\n\n\n

In the mid-1970s, the\nNational Commission for the Protection of Human Subjects of Biomedical and\nBehavioral Research set out to develop a set of regulations to ensure that unethical\nconduct of research no longer happened. After years of work, the Commission\ndeveloped an ethical guideline, the Belmont Report, which describes the guiding\nprinciples for ethical conduct of research in the United States. The Belmont\nReport outlined three main tenants: respect for persons, beneficence, and justice.\n<\/p>\n\n\n\n