Protecting Participants Is Not the Top Priority in Clinical Research.

This Viewpoint discusses the need to protect participants in clinical research and the opportunity to address this issue as the World Medical Association works to revise its Declaration of Helsinki, which governs medical research ethics.

The Belmont Report at 40: Reckoning With Time.

It was the summer of 1972 when a stunned nation first learned of the infamous Tuskegee Syphilis Study, during which hundreds of poor, disease-stricken black men from Macon County Alabama, had been deliberately left untreated for 40 years. Coming on the heels of multiple, earlier examples of unethical human experimentation, the Tuskegee Syphilis Study made it plain that the moral foundation of human subject research was in desperate need of repair. Blind reliance on the Nuremberg Code and the Declaration of Helsinki was no longer going to suffice. It was against this backdrop that Congress resolved to act. Numerous hearings and multiple spirited discussions later, an agreement was struck to constitute the "Commission." The outgrowth of a retreat held at the Smithsonian Institution's Belmont Conference Center, the Belmont Report lays out a principled analytical framework to "guide the resolution of ethical problems arising from research involving human subjects." Durable and ever-present, the Belmont Report, which is the foundational document that reset the ethics of human subject research, must now reckon with all-important novel issues of the day that could not have been foreseen by its drafters.

Biospecimen research and the law.

In the well-known case of Henrietta Lacks, cells from her tumor were taken without consent and used more than 70 years ago to create the first immortal human cell line ("HeLa" cells). That event led to many scientific breakthroughs and to the debate about the ethics of consent and requirements for compensation. May 2024 saw two decisions by US federal courts-one related to Lacks-that could narrow the scope of research allowed on tissues obtained without consent and on nonidentified tissues, with implications for biomedicine.

Ethically cleared to launch?

Rules are needed for human research in commercial spaceflight.

Streamlining ethical review.

The review system for human subjects research in the United States has been widely criticized in recent years for requirements that delay research without improving human subject protections. Any major reformulation of regulations may take some time to implement. However, current regulations often allow for streamlined ethics review that does not jeopardize-and may improve-protections for research participants. The authors discuss underutilized options, including research that need not be classified as human subjects research, categories of studies that can be exempt from ethical review, studies that need only undergo expedited review by 1 institutional review board (IRB) member, and simplifying reviews of multicenter research by using the IRB of 1 institution. The authors speculate on multiple reasons for the underuse of these mechanisms and exhort IRBs and researchers to take advantage of these important opportunities to improve the review process.

Protecting Research Subjects During a Pandemic.

This commentary discusses twelve stories in which people who are involved in institutional review board (IRB) administration or serve as IRB members tell the stories of how the COVID-19 pandemic affected their work and lives. Among the aspects of these stories it highlights are the need to focus on the well-being of the institution's employees, and how issues involving protecting vulnerable subjects might relate to current policy debates about underserved communities. The final portion of this commentary focuses in particular on how one might measure success for a program in protecting its research subjects during a pandemic.

The use of human biospecimens for research.

This discussion presents many of the ethical, legal, and financial issues that underlie the contemporary regulatory framework for research with human biospecimens. Some considerations, such as claims of donor control over their biospecimens, could potentially constrain researchers' freedom of action. We first consider concepts underlying consent to donate biospecimens for research. A requirement to obtain consent for donation of a biospecimen could conceptually be based upon the autonomy of the donor, or on property rights of the donor, or a combination of both concepts. If these concepts affect how consent is implemented, it could have significant downstream consequences for research and researchers. We present elements of the revision of the common rule that affect the use of human biospecimens including the current consent regulations based on transparency and autonomy, and the distinction between consent for, and ownership of, biospecimens. One of the major judicial opinions that denied property rights for biospecimens is described together with some implications for the research community of attributing ownership of biospecimens to their donors. We then consider transactional aspects of biospecimen donation. Considering biospecimens as a negotiable commodity presents both constraints and opportunities for donors and researchers. Compensation for biospecimens can be negotiated under contract law. Allowing donor control of the secondary research use of deidentified biospecimens could have an inhibiting effect on research. If donors possessed such control, even deidentification would not necessarily eliminate their ability to influence future research. Accordingly, new models of biospecimen donation are appearing in which the research community will have a substantial interest.

The vulnerability of the very sick.

When seriously ill patients for whom existing treatments are inadequate are invited to participate in clinical trials that offer a new treatment, should those persons be considered "vulnerable"? And if so, what additional protections should they be accorded? This article attempts to provide some answers.

Use of PRO Measures to Inform Tolerability in Oncology Trials: Implications for Clinical Review, IND Safety Reporting, and Clinical Site Inspections.

Cancer therapeutics frequently lead to symptomatic adverse events (AE) that can affect treatment tolerability. The NCI has developed the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to assess symptomatic AEs by direct patient self-report. Although longitudinal assessment of patient-reported symptomatic AEs holds promise to better inform treatment tolerability, using patient-reported outcome (PRO) measures to assess symptomatic AEs has raised several regulatory and good clinical practice issues among those who conduct cancer clinical trials. These include concerns regarding trial monitoring, clinical review of PRO results by investigators and delegated clinical staff, whether PRO data on symptomatic AEs require investigational new drug (IND) safety reporting, and how the trial conduct and resultant PRO data will be assessed during clinical investigator site inspections. This article addresses current thinking regarding these issues in cancer clinical trials from the FDA, the NCI, and the Office for Human Research Protections. PRO measures, such as PRO-CTCAE, that assess symptomatic AEs in cancer trials are considered similar to other PRO assessments of symptoms, function, and health-related quality of life and can generate complementary data that may inform tolerability. Clarity on operational concerns related to incorporating PRO measures to inform tolerability is critical to continue the advancement of rigorous PRO assessment in cancer clinical trials. Clin Cancer Res; 24(8); 1780-4. ©2017 AACRSee related commentary by Nipp and Temel, p. 1777.