New Regulations and Code of Ethics for Research in the 21st Century

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Most of the changes to the Common Rule will go into effect in January 2018.
Most of the changes to the Common Rule will go into effect in January 2018.

Clinical trial research has formed the basis for medical advances and therapeutic developments since 1997, when the federal government passed legislation requiring registration of all human research. Although human trials had been conducted as far back as biblical times, James Lind is credited with the first clinical trial to use control subjects in 1747.1,2 But as medicine moved into the 20th century and more trials were initiated using larger numbers of "subjects," the ethics and procedures of these investigations were increasingly called into question.

The Legacy of the Tuskegee Syphilis Study

The tragedy of the Tuskegee Syphilis Experiment, conducted from 1932 to 1972 in uneducated blacks in Alabama, ultimately led to public exposure of the serious lack of ethics of clinical trial research of the time.3-5 During that trial, which was designed to study the effects of untreated syphilis in the American Negro male, patients were denied treatment as the disease progressed for decades, although penicillin was a known cure by 1947.3-5 The trial ultimately resulted in the deaths of 28 of 399 participants from syphilis, 100 from other causes, and the infection of 40 wives and 19 children.3

 

This trial spotlighted the need for ethical standards in the conduct of clinical trials moving forward, particularly with regard to informed consent. The Belmont Report came out in 1979, providing the first guidelines toward federal protection of participants in clinical trials and a basic set of standards for institutional review board (IRB) procedures in the design of clinical trial research.6,7 The Common Rule was proposed in 1981 by the US Department of Health and Human Services, along with 15 federal agencies, for the ethical conduct of research.

Two important reforms were introduced in late 2016 and early 2017 to address the ethical challenges of the future and drive research that can improve the quality of human life. The first was enactment of the 21st Century Cures Act by Congress, signed into law by President Obama in December 2016.8 This act provides funding for 3 major initiatives: the cancer "moonshot" project, brain research for Alzheimer's disease and other neurological disorders, and the Precision Medicine Initiative, designed to shift the attention of clinical treatment to targeted therapies for better individual outcomes.

The second reform was extensive revision to the Common Rule published on January 19, 2017, after 6 years of extensive review and public discussion, to further define safe and ethical conduct in the modern landscape that includes cloning, introduction of nonbiologic tissue, and the medical extension of life by multiple standards.7-9

The Common Rule Revisions

In the last 2 decades, new, digital technologies that vastly expanded the type and amount of data collected and stored, the rapidity of access to it, and the development of genetic research, biobanking of human tissue samples, and novel, nonbiologic therapies have presented unlimited potential directions for medical research.

The 2017 revisions to the Common Rule deal largely with improving the transparency and clarity of intended uses under the current standard of informed consent while introducing a new concept of "broad consent" that can significantly expand the reach of research that continues to yield new and important information.

Changes to the Common Rule include7-9:

1. Revised requirements for "informed consent," specifically targeting the understandability of the current language to direct that it must include "information that a reasonable person would want to have in order to make an informed decision" to participate in a trial.

2. New, "broad consent" guidelines for the use of identifiable information and samples in secondary research: This is designed to facilitate the continued expansion of primary research into areas that can continue to yield information from the original samples and data collected. To meet this requirement, an IRB must provide a general description of all types of research that may be conducted, what types of information and samples may be used, and how long these may be held in storage or in use. In addition, they must provide a statement telling the participant that they will not be informed of future research or the outcomes.

3. Directives to promote single-IRB oversight of multicenter clinical trials: The purpose of this is to reduce the significant waste of time and resources spent on multiple IRB reviews of the same study. The one concern is that university-based IRBs would not have the infrastructure to take on an expanded role, and so the implementation for this revision to the Common Rule has been pushed out to January 2020 to consider alternatives.

4. Expanded categories of research that are exempt from meeting guidelines, to include surveys, interviews, and other forms of free communication between investigators and adults: Additional exempted forms of study include aptitude testing, observation and recording of speech and behavior in schools and public places, implementation of benign behavioral interventions, secondary analysis of data, and other research activities deemed "low risk."

5. Removal of stipulations for continued annual review of low risk research.

It is hoped that these changes, most of which go into effect in January 2018, will help shape future research that opens the doors for the discovery of new therapies and reduces disease and its consequences for a new generation without undue harm to the participants of clinical trial research.

References

  1. ClinicalTrials.gov. History, policies and laws. https://clinicaltrials.gov/ct2/about-site/history#CongressPassesLawFDAMA. Accessed November 14, 2017.
  2. Avail Clinical Research. A historic timeline of clinical trials. https://www.availclinical.com/clinical-study/clinical-trials-history/ Accessed November 14, 2017.
  3. Explorable. Tuskegee Syphilis Study. https://explorable.com/tuskegee-syphilis-study. Accessed November 14, 2017.
  4. Centers for Disease Control and Prevention. Tuskegee Study, 1932-1972. https://www.cdc.gov/tuskegee/index.html. Updated December 30, 2013. Accessed November 14, 2017.
  5. Centers for Disease Control and Prevention. The Tuskegee timeline. https://www.cdc.gov/tuskegee/timeline.htm. Updated August 30, 2017. Accessed November 14, 2017.
  6. Department of Health, Education, and Welfare; National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report. Ethical principles and guidelines for the protection of human subjects of research. J Am Coll Dent. 2014;81:4-13.
  7. Hodge JG, Gostin LO. Revamping the US Federal Common Rule: modernizing human participant research regulations. JAMA. 2017;317:1521-1522.
  8. Burris JF, Puglisi JT. Impact of federal regulatory changes on clinical pharmacology and drug development: the Common Rule and the 21st Century Cures Act [published online October 5, 2017]. J Clin Pharmacol. doi: 10.1002/jcph.1026
  9. Hudson KL, Collins FS. Bringing the Common Rule into the 21st Century. N Engl J Med. 2015;373:2293-2296. 
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