Characterization of key information sections in informed consent forms posted on ClinicalTrials.gov.

Introduction: Recent revisions to the US Federal Common Rule governing human studies funded or conducted by the federal government require the provision of a "concise and focused" key information (KI) section in informed consent forms (ICFs). We performed a systematic study to characterize KI sections of ICFs for federally funded trials available on ClinicalTrials.gov. Methods: We downloaded ICFs posted on ClinicalTrials.gov for treatment trials initiated on or after the revised Common Rule effective date. Trial records (n = 102) were assessed by intervention type, study phase, recruitment status, and enrollment size. The ICFs and their KI sections, if present, were characterized by page length, word count, readability, topic, and formatting elements. Results: Of the 102 trial records, 76 had identifiable KI sections that were, on average, 10% of the total length of full ICF documents. KI readability grade level was not notably different from other sections of ICFs. Most KI sections were distinguished by section headers and included lists but contained few other formatting elements. Most KI sections included a subset of topics consistent with the basic elements of informed consent specified in the Common Rule. Conclusion: Many of the KI sections in the study sample aligned with practices suggested in the preamble to the revised Common Rule. Further, our results suggest that some KI sections were tailored in study-specific ways. Nevertheless, guidelines on how to write concise and comprehensible KI sections would improve the utility and readability of KI sections.

Terms and conditions apply: an ethical analysis of mobile health user agreements in research.

Mobile health (mHealth) technologies raise unique risks to user privacy and confidentiality that are often embedded in lengthy and complex Privacy Policies, Terms of Use, and End User License Agreements. We seek to improve the ethical review of these documents ('user agreements') and their risks in research using mHealth technologies by providing a framework for identifying when these risks are research risks, categorizing the key information in these agreements under relevant ethical and regulatory categories, and proposing strategies to mitigate them. MHealth user agreements typically describe the nature of the data collected by mHealth technologies, why or for what purposes user data are collected and shared, who will have access to the different types of data collected, and may include exculpatory language. The risks raised by data collection and sharing typically increase with the sensitivity and identifiability of the data and vary by whether data are shared with researchers, the technology developer, and/or third-party entities. The most important risk mitigation strategy is disclosure of the key information found in user agreements to participants during the research consent process. In addition, researchers should prioritize mHealth technologies with favorable risk-benefit balances.

Ensuring the Scientific Value and Feasibility of Clinical Trials: A Qualitative Interview Study.

BACKGROUND: Ethical and scientific principles require that clinical trials address an important question and have the resources needed to complete the study. However, there are no clear standards for review that would ensure that these principles are upheld. METHODS: We conducted semi-structured interviews with a convenience sample of nineteen experts in clinical trial design, conduct, and/or oversight to elucidate current practice and identify areas of need with respect to ensuring the scientific value and feasibility of clinical trials prior to initiation and while ongoing. We used a priori and grounded theory to analyze the data and constant comparative method to induce higher order themes. RESULTS: Interviewees perceived determination of scientific value as the responsibility of the investigator and, secondarily, other parties who review or oversee research. Interviewees reported that ongoing trials are rarely reevaluated due to emerging evidence from external sources, evaluation is complex, and there would be value in the development of standards for monitoring and evaluating evidence systematically. Investigators, IRBs, and/or data monitoring committees (DMCs) could undertake these responsibilities. Feasibility assessments are performed but are typically inadequate; potential solutions are unclear. CONCLUSIONS: There are three domains where current approaches are suboptimal and in which further guidance is needed. First, who has the responsibility for conducting scientific review, whether it be the investigator, IRB, and/or DMC is often unclear. Second, the standards for scientific review (e.g., appropriate search terms, data sources, and analytic plan) should be defined. Third, guidance is needed on the evaluation of ongoing studies in light of potentially new and evolving evidence, with particular reference to evidence from outside the trial itself.

The oversight of autonomous artificial intelligence: lessons from nurse practitioners as physician extenders.

The development of autonomous artificial intelligence (A-AI) products in health care raises novel regulatory challenges, including how to ensure their safety and efficacy in real-world settings. Supplementing a device-centered regulatory scheme with a regulatory scheme that considers A-AI products as a 'physician extender' may improve the real-world monitoring of these technologies and produce other benefits, such as increased access to the services offered by these products. In this article, we review the three approaches to the oversight of nurse practitioners, one type of physician extender, in the USA and extrapolate these approaches to produce a framework for the oversight of A-AI products. Under the framework, the US Food and Drug Administration would evaluate A-AI products and determine whether they are allowed to operate independently of physician oversight; required to operate under some physician oversight via a 'collaborative protocol' model; or required to operate under direct physician oversight via a 'supervisory protocol' model.

When Is a Change Significant? The Update Problem of Apps in Medical and Behavioral Research.

Digital applications (apps) are commonly used across the research ecosystem. While apps are frequently updated in the course of clinical and behavioral research, there is limited guidance as to when an app update should trigger action related to human research participant protections and who should be responsible for monitoring and reviewing these updates. We term this the "update problem" and argue that, while it is the principal investigator's duty to track all relevant updates, the level of involvement and re-review by the institutional review board (IRB) of an approved research protocol should vary depending on whether the update may be classified as minor, not minor, or significant. Minor updates require at most annual notification of the IRB, updates that are not minor require prompt notification of the IRB, and significant updates may require full board re-review or another response. We also suggest how these policies might be implemented.

Evaluating the frequency of English language requirements in clinical trial eligibility criteria: A systematic analysis using ClinicalTrials.gov.

BACKGROUND: A number of prior studies have demonstrated that research participants with limited English proficiency in the United States are routinely excluded from clinical trial participation. Systematic exclusion through study eligibility criteria that require trial participants to be able to speak, read, and/or understand English affects access to clinical trials and scientific generalizability. We sought to establish the frequency with which English language proficiency is required and, conversely, when non-English languages are affirmatively accommodated in US interventional clinical trials for adult populations. METHODS AND FINDINGS: We used the advanced search function on ClinicalTrials.gov specifying interventional studies for adults with at least 1 site in the US. In addition, we used these search criteria to find studies with an available posted protocol. A computer program was written to search for evidence of English or Spanish language requirements, or the posted protocol, when available, was manually read for these language requirements. Of the 14,367 clinical trials registered on ClinicalTrials.gov between 1 January 2019 and 1 December 2020 that met baseline search criteria, 18.98% (95% CI 18.34%-19.62%; n = 2,727) required the ability to read, speak, and/or understand English, and 2.71% (95% CI 2.45%-2.98%; n = 390) specifically mentioned accommodation of translation to another language. The remaining trials in this analysis and the following sub-analyses did not mention English language requirements or accommodation of languages other than English. Of 2,585 federally funded clinical trials, 28.86% (95% CI 27.11%-30.61%; n = 746) required English language proficiency and 4.68% (95% CI 3.87%-5.50%; n = 121) specified accommodation of other languages; of the 5,286 industry-funded trials, 5.30% (95% CI 4.69%-5.90%; n = 280) required English and 0.49% (95% CI 0.30%-0.69%; n = 26) accommodated other languages. Trials related to infectious disease were less likely to specify an English requirement than all registered trials (10.07% versus 18.98%; relative risk [RR] = 0.53; 95% CI 0.44-0.64; p < 0.001). Trials related to COVID-19 were also less likely to specify an English requirement than all registered trials (8.18% versus 18.98%; RR = 0.43; 95% CI 0.33-0.56; p < 0.001). Trials with a posted protocol (n = 366) were more likely than all registered clinical trials to specify an English requirement (36.89% versus 18.98%; RR = 1.94, 95% CI 1.69-2.23; p < 0.001). A separate analysis of studies with posted protocols in 4 therapeutic areas (depression, diabetes, breast cancer, and prostate cancer) demonstrated that clinical trials related to depression were the most likely to require English (52.24%; 95% CI 40.28%-64.20%). One limitation of this study is that the computer program only searched for the terms "English" and "Spanish" and may have missed evidence of other language accommodations. Another limitation is that we did not differentiate between requirements to read English, speak English, understand English, and be a native English speaker; we grouped these requirements together in the category of English language requirements. CONCLUSIONS: A meaningful percentage of US interventional clinical trials for adults exclude individuals who cannot read, speak, and/or understand English, or are not native English speakers. To advance more inclusive and generalizable research, funders, sponsors, institutions, investigators, institutional review boards, and others should prioritize translating study materials and eliminate language requirements unless justified either scientifically or ethically.

Navigating the ethics of remote research data collection.

COVID-19 has accelerated broad trends already in place toward remote research data collection and monitoring. This move implicates novel ethical and regulatory challenges which have not yet received due attention. Existing work is preliminary and does not seek to identify or grapple with the issues in a rigorous and sophisticated way. Here, we provide a framework for identifying and addressing challenges that we believe can help the research community realize the benefits of remote technologies while preserving ethical ideals and public trust. We organize issues into several distinct categories and provide points to consider in a table that can help facilitate ethical design and review of research studies using remote health instruments.

Online Research Participant Communication: Balancing Benefits and Risks.

Online communication has emerged as an important vehicle for participant interaction during the course of clinical research. At the same time, such communication has been identified as a source of risks both for participants and the scientific integrity of clinical trials. Although strategies for mitigating these risks have become a focus in the research community, missing from the discussion has been a sustained and sympathetic effort to understand the various benefits of online communication for participants themselves. In this article, we provide a taxonomy of the benefits of online communication for participants and argue that attempts to mitigate the risks of online communication by discouraging or placing limits on such communication are generally unadvisable. Instead, we advance a context-sensitive approach that emphasizes education and several actionable recommendations for preserving the benefits of online participant communities while mitigating the risks.