Volume 33, Issue 4, October 2023, Pages 349-357Author links open overlay panel, ,

The concept of informed consent has evolved considerably over the course of the 20th century, leading to its establishment as a foundational ethical principle for the conduct of biomedical research in the United States. Even though it is now a highly regulated part of cancer research, the process of obtaining informed consent is often impeded by systemic, clinician, and patient factors that require both small- and large-scale intervention. New challenges and considerations continue to emerge due to innovations in clinical trial design, increases in utilization of genomic sequencing, and advances in genomic editing and artificial intelligence. We present a review of the history, policy, pragmatic challenges, and evolving role of the central ethical tenet of informed consent in clinical trials.

Section snippetsA Look Back: History and Policy

Informed consent, a pivotal ethical concept in biomedical research, has undergone significant development over the 20th century (Fig. 1). In the middle of the century, revelations about shocking human experimentation in Nazi Germany led to the codification of the rights of human participants in research. Nazi physicians violated the human rights of thousands of victims as they conducted medical studies without participant consent, some of which resulted in sterilization, considerable morbidity,

Exemptions and Waivers

Despite the legal requirements for documented informed consent, even in the modern era, many studies are done without informed consent. In one systematic review of the top 500 most highly cited randomized, controlled trials published from 2014 to 2018, researchers found that almost 10% did not obtain complete informed consent.9 In another systematic review of 103 pragmatic and comparative effectiveness randomized controlled trials published in 2014 or 2017, 22% similarly did not obtain informed

Informed Consent in Practice

Even in cancer research involving human subjects where prospective written informed consent is obtained without exemption or waiver, it is often imperfect. There are a range of different factors that can inhibit high-quality informed consent, ranging from the systemic level to that of the individual clinician or individual patient and their families or caregivers (Fig. 2).13 On the systemic level, large obstacles include time, infrastructure, and resources, which may make it difficult for

Consent in an Era of Novel Trial Designs

As the lines between research and clinical care are blurred within learning health systems, many studies that meet Common Rule criteria and pose minimal risk may not legally require specific informed consent processes.31 Large quality improvement studies that satisfy the 4 Common Rule criteria would not otherwise be practicably able to be carried out, and thus qualify for informed consent waivers. Low-risk pragmatic trials, or trials where standard-of-care alternatives are compared with

Genomic Sequencing

New challenges are emerging for informed consent with the development of advanced technologies. The 2018 revision to the Common Rule, for the first time, addresses some considerations associated with ethical research involving genomic sequencing. These studies, which are felt to pose no more than minimal risk, are often conducted with broad consent, in which a person might consent to their biospecimens being collected and stored as part of an effort to build a “biobank.” Biobank specimens might

Conclusions

Throughout the 20th century, informed consent became established as a central ethical principle in biomedical research in the United States. Although not perfectly executed in practice, it has become a highly regulated part of cancer research. Potential best practices for informed consent in cancer clinical trials include improving use of novel audio-visual aids and teach-back methods, patient navigation, increasing readability of consent forms and materials, and tailored training and

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