The Integration of Clinical Trials With the Practice of Medicine: Repairing a House Divided.

Importance: Optimal health care delivery, both now and in the future, requires a continuous loop of knowledge generation, dissemination, and uptake on how best to provide care, not just determining what interventions work but also how best to ensure they are provided to those who need them. The randomized clinical trial (RCT) is the most rigorous instrument to determine what works in health care. However, major issues with both the clinical trials enterprise and the lack of integration of clinical trials with health care delivery compromise medicine's ability to best serve society. Observations: In most resource-rich countries, the clinical trials and health care delivery enterprises function as separate entities, with siloed goals, infrastructure, and incentives. Consequently, RCTs are often poorly relevant and responsive to the needs of patients and those responsible for care delivery. At the same time, health care delivery systems are often disengaged from clinical trials and fail to rapidly incorporate knowledge generated from RCTs into practice. Though longstanding, these issues are more pressing given the lessons learned from the COVID-19 pandemic, heightened awareness of the disproportionate impact of poor access to optimal care on vulnerable populations, and the unprecedented opportunity for improvement offered by the digital revolution in health care. Four major areas must be improved. First, especially in the US, greater clarity is required to ensure appropriate regulation and oversight of implementation science, quality improvement, embedded clinical trials, and learning health systems. Second, greater adoption is required of study designs that improve statistical and logistical efficiency and lower the burden on participants and clinicians, allowing trials to be smarter, safer, and faster. Third, RCTs could be considerably more responsive and efficient if they were better integrated with electronic health records. However, this advance first requires greater adoption of standards and processes designed to ensure health data are adequately reliable and accurate and capable of being transferred responsibly and efficiently across platforms and organizations. Fourth, tackling the problems described above requires alignment of stakeholders in the clinical trials and health care delivery enterprises through financial and nonfinancial incentives, which could be enabled by new legislation. Solutions exist for each of these problems, and there are examples of success for each, but there is a failure to implement at adequate scale. Conclusions and Relevance: The gulf between current care and that which could be delivered has arguably never been wider. A key contributor is that the 2 limbs of knowledge generation and implementation-the clinical trials and health care delivery enterprises-operate as a house divided. Better integration of these 2 worlds is key to accelerated improvement in health care delivery.

Managing community engagement in research in Uganda: insights from practices in HIV/AIDS research.

BACKGROUND: Community engagement (CE) in research is valuable for instrumental and intrinsic reasons. Despite existing guidance on how to ensure meaningful CE, much of what it takes to achieve this goal differs across settings. Considering the emerging trend towards mandating CE in many research studies, this study aimed at documenting how CE is conceptualized and implemented, and then providing context-specific guidance on how researchers and research regulators in Uganda could think about and manage CE in research. METHODS: We conducted qualitative interviews and focus group discussions involving forty-one respondents who were experienced in HIV/AIDS biomedical research involving CE. Thirty-eight of these were directly or indirectly associated with Uganda's leading research institution in the field of HIV/AIDS. They included Principal Investigators, Community Liaisons Officers, Research Ethics Committee members and Community Advisory Board Members. Three respondents were from Uganda National Council for Science and Technology. Data were collected between August 2019 and August 2020, using audio-taped focus group discussions and key informant interviews, transcribed and analyzed manually to generate themes and subthemes. RESULTS: Three major themes emerged: goals or value of CE; the means of CE, and, the evaluation of CE. Goals or value of CE generated four subthemes representing the overarching goals of CE: (1) Promote communities' agency; (2) Generate and sustain trust; (3) Protect and promote communities' rights and interests; and, (4) Help studies optimize participation in the form of enrolment and retention of participants. What usually comes under the nomenclatures of methods, strategies, and approaches of CE, such as town-hall meetings, sports events, drama, and the like, should simply be understood as the means of CE, and it is not desirable to hold pre-conceived and fixed ideas about the best means to conduct CE in research since a lot depend on the context. Finally, the study found that despite CE's critical importance, which suggests the need to track and evaluate it, CE is currently intermittently evaluated, and for inadequate motivations. CONCLUSIONS: Existing guidance on how to conduct robust CE in research is no substitute for creativity, flexibility, and reflexivity on the part of both researchers and research regulators.

Immunity certification for COVID-19: ethical considerations.

Restrictive measures imposed because of the coronavirus disease 2019 (COVID-19) pandemic have resulted in severe social, economic and health effects. Some countries have considered the use of immunity certification as a strategy to relax these measures for people who have recovered from the infection by issuing these individuals a document, commonly called an immunity passport. This document certifies them as having protective immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes COVID-19. The World Health Organization has advised against the implementation of immunity certification at present because of uncertainty about whether long-term immunity truly exists for those who have recovered from COVID-19 and concerns over the reliability of the proposed serological test method for determining immunity. Immunity certification can only be considered if scientific thresholds for assuring immunity are met, whether based on antibodies or other criteria. However, even if immunity certification became well supported by science, it has many ethical issues in terms of different restrictions on individual liberties and its implementation process. We examine the main considerations for the ethical acceptability of immunity certification to exempt individuals from restrictive measures during the COVID-19 pandemic. As well as needing to meet robust scientific criteria, the ethical acceptability of immunity certification depends on its uses and policy objectives and the measures in place to reduce potential harms, and prevent disproportionate burdens on non-certified individuals and violation of individual liberties and rights.

Les restrictions imposées dans le cadre de la lutte contre la pandémie de maladie à coronavirus 2019 (COVID-19) ont eu de lourdes conséquences économiques, sociales et sanitaires. Certains pays ont envisagé la mise en place d'une stratégie visant à alléger ces restrictions pour les individus guéris en leur octroyant un document communément appelé «passeport d'immunité¼. Ce document atteste qu'ils ont développé une immunité protectrice contre le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2), le virus à l'origine de la COVID-19. L'Organisation mondiale de la Santé a déconseillé l'usage du certificat d'immunité pour l'instant, car l'incertitude demeure quant à l'existence réelle d'une immunité à long terme pour ceux qui se sont remis de la COVID-19. En outre, la fiabilité des tests sérologiques censés déterminer si l'individu est immunisé n'est pas avérée. Un tel certificat ne peut être instauré que si les seuils scientifiques en matière d'immunité sont respectés, qu'ils soient fondés sur les anticorps ou sur d'autres critères. Néanmoins, même si le certificat d'immunité est désormais bien accepté par la science, il s'accompagne de nombreuses questions d'ordre éthique en ce qui concerne la limitation des libertés individuelles et la mise en œuvre. Dans le présent document, nous examinons les principales considérations à prendre en compte pour garantir l'acceptabilité éthique du certificat d'immunité visant à lever les mesures de restriction pour certaines personnes durant la pandémie de COVID-19. Cette acceptabilité éthique dépend non seulement de son degré de conformité à des critères scientifiques stricts, mais aussi de son usage, des objectifs politiques ainsi que des mesures mises en place pour atténuer les préjudices potentiels et éviter d'imposer une charge disproportionnée sur les individus dépourvus de certificat, ou de bafouer les droits et libertés de tout un chacun.

Las medidas restrictivas impuestas a causa de la pandemia de la enfermedad coronavirus de 2019 (COVID-19) han tenido graves efectos sociales, económicos y sanitarios. Algunos países han considerado la posibilidad de utilizar la certificación de inmunidad como estrategia para flexibilizar dichas medidas para las personas que se han recuperado de la infección mediante la expedición a dichas personas de un documento, comúnmente denominado pasaporte de inmunidad. Este documento certifica que han desarrollado inmunidad protectora contra el coronavirus-2 del síndrome respiratorio agudo severo (SARS-CoV-2), el virus que causa la COVID-19. La Organización Mundial de la Salud ha desaconsejado la aplicación de la certificación de la inmunidad en la actualidad debido a la incertidumbre sobre si existe realmente una inmunidad a largo plazo para quienes se han recuperado de la COVID-19 y a las preocupaciones sobre la fiabilidad del método de prueba serológica propuesto para determinar la inmunidad. La certificación de la inmunidad solo puede considerarse si se cumplen los umbrales científicos para asegurar la inmunidad, ya sea que se basen en anticuerpos o en otros criterios. Sin embargo, incluso si la certificación de la inmunidad llegara a estar bien respaldada por la ciencia, tiene muchas cuestiones éticas en cuanto a las diferentes restricciones de las libertades individuales y su proceso de aplicación. Examinamos las principales consideraciones sobre la aceptabilidad ética de la certificación de la inmunidad para eximir a los individuos de las medidas restrictivas durante la pandemia de la COVID-19. Además de necesitar cumplir criterios científicos sólidos, la aceptabilidad ética de la certificación de inmunidad depende de sus usos y objetivos de política y de las medidas que se apliquen para reducir los posibles daños y evitar que se impongan cargas desproporcionadas a las personas que no cuenten con dicha certificación y se violen las libertades y derechos individuales.

Randomized comparison of two interventions to enhance understanding during the informed consent process for research.

BACKGROUND/AIMS: Many investigators have tested interventions to improve research participant understanding of information shared during the informed consent process, using a variety of methods and with mixed results. A valid criticism of most consent research is that studies are often conducted in simulated research settings rather than ongoing clinical studies. The present study rigorously tested two simple and easily adoptable strategies for presenting key consent information to participants eligible to enroll in six actual clinical trials (i.e. six parent studies). METHODS: In collaboration with the study team from each parent study, we developed two consent interventions: a fact sheet and an interview-style video. The content of each of the intervention was based on the information shared in the consent form approved for each parent study. Participants were randomized to the standard consent process, or to one of the two interventions. Once exposed to the assigned consent mode, participants were asked to complete an assessment of understanding. The study was powered to determine whether those exposed to the fact sheet or video performed better on the consent assessment compared to those exposed to the standard consent. We also assessed participant satisfaction with the consent process. RESULTS: A total of 284 participants were randomized to one of the three consent arms. Assessments of understanding were completed with a total of 273 participants from July 2017 to April 2019. Participants exposed to the video had better understanding scores compared to those exposed to the standard consent form process (p value = 0.020). Participants were more satisfied with the video when compared to the standard consent. Participants who received the fact sheet did not achieve higher overall understanding or satisfaction scores when compared to the standard consent process. CONCLUSION: This randomized study of two novel consent interventions across six different clinical trials demonstrated a statistically significant difference in participant understanding based on overall scores among those exposed to the video intervention compared to those exposed to the standard consent.

Ethics challenges and guidance related to research involving adolescent post-abortion care: a scoping review.

INTRODUCTION: An increase in post abortion care (PAC) research with adolescents, particularly in low- and middle-income countries, has brought to attention several associated research ethics challenges. In order to better understand the ethics context of PAC research with adolescents, we conducted a scoping review of published literature. METHODS: Following a systematic search of PubMed, HINARI, and Google Scholar, we analysed articles meeting inclusion criteria to determine common themes across both the ethical challenges related to PAC research with adolescents and any available guidance on the identified challenges. RESULTS: The literature search identified an initial 3321 records of which 14 were included in analysis following screening. Several ethical challenges stem from abortion being a controversial, sensitive, and stigmatized topic in many settings. Ethical dilemmas experienced by researchers conducting adolescent PAC research included: difficulties in convincing local health providers to permit PAC research; challenges in recruiting and seeking consent due to sensitivity of the subject; effectively protecting confidentiality; managing negative effects of interventions; creating a non-prejudicial atmosphere for research; managing emotional issues among adolescents; and dealing with uncertainty regarding the role of researchers when observing unethical health care practices. Suggested strategies for addressing some of these challenges include: using several sources to recruit study participants, using research to facilitate dialogue on abortion, briefing health workers on any observed unethical practices after data collection, fostering a comprehensive understanding of contextual norms and values, selecting staff with experience working with study populations, and avoiding collection of personal identifiers. CONCLUSION: Addressing ethical challenges that researchers face when conducting PAC research with adolescents requires guidance at the individual, institutional, community, and international levels. Overall, despite the documentation of challenges in the published literature, guidance on handling several of these ethics challenges is sparse. We encourage further research to clarify the identified challenges and support the development of formal guidance in this area.

A randomized study of multimedia informational aids for research on medical practices: Implications for informed consent.

BACKGROUND/AIMS: Participant understanding is a key element of informed consent for enrollment in research. However, participants often do not understand the nature, risks, benefits, or design of the studies in which they take part. Research on medical practices, which studies standard interventions rather than new treatments, has the potential to be especially confusing to participants because it is embedded within usual clinical care. Our objective in this randomized study was to compare the ability of a range of multimedia informational aids to improve participant understanding in the context of research on medical practices. METHODS: We administered a web-based survey to members of a proprietary online panel sample selected to match national US demographics. Respondents were randomized to one of five arms: four content-equivalent informational aids (animated videos, slideshows with voice-over, comics, and text) and one no-intervention control. We measured knowledge of research on medical practices using a summary knowledge score from 10 questions based on the content of the informational aids. We used analysis of variance and paired t-tests to compare knowledge scores between arms. RESULTS: There were 1500 completed surveys (300 in each arm). Mean knowledge scores were highest for the slideshows with voice-over (65.7%), followed by the animated videos (62.7%), comics (60.7%), text (57.2%), and control (50.3%). Differences between arms were statistically significant except between the slideshows with voice-over and animated videos and between the animated videos and comics. Informational aids that included an audio component (animated videos and slideshows with voice-over) had higher knowledge scores than those without an audio component (64.2% vs 59.0%, p < .0001). There was no difference between informational aids with a character-driven story component (animated videos and comics) and those without. CONCLUSION: Our results show that simple multimedia aids that use a dual-channel approach, such as voice-over with visual reinforcement, can improve participant knowledge more effectively than text alone. However, the relatively low knowledge scores suggest that targeted informational aids may be needed to teach some particularly challenging concepts. Nonetheless, our results demonstrate the potential to improve informed consent for research on medical practices using multimedia aids that include simplified language and visual metaphors.

A Journey in Public Health Ethics.

While medical ethics has a long history, and research ethics guidance emerged more formally in the 1960s and 1970s, frameworks for public health ethics began to appear in the 1990s. The author's thinking about public health ethics evolved from consideration of some of the ethics and policy questions surfacing regularly in the HIV/AIDS epidemic. This essay discusses some of the shared commitments of public health and ethics, as well as how one might apply an ethics lens to public health programs, both generally and in the contexts of public health preparedness and obesity prevention.

A pilot study of simple interventions to improve informed consent in clinical research: feasibility, approach, and results.

BACKGROUND: Research suggests that participants do not always adequately understand studies. While some consent interventions increase understanding, methodologic challenges have been raised in studying consent outside of actual trial settings. This study examined the feasibility of testing two consent interventions in actual studies and measured effectiveness of interventions in improving understanding. METHODS: Participants enrolling in any of eight ongoing clinical trials were sequentially assigned to one of three different informed consent strategies for enrollment in their clinical trial. Control participants received standard consent procedures for their trial. Participants in the first intervention arm received a bulleted fact sheet summarizing key study information. Participants in the second intervention arm received the bulleted fact sheet and also engaged in a feedback Q&A session. Later, patients answered closed- and open-ended questions to assess patient understanding and literacy. Descriptive statistics, Wilcoxon -Mann -Whitney and Kruskal-Wallis tests were generated to assess correlations; regression analysis determined predictors of understanding. RESULTS: 144 participants enrolled. Using regression analysis, participants receiving the second intervention scored 7.6 percentage points higher (p = .02) on open-ended questions about understanding than participants in the control, although unadjusted comparisons did not reach statistical significance. CONCLUSIONS: Our study supports the hypothesis that patients receiving both bulleted fact sheets and a Q&A session had higher understanding compared to standard consent. Fact sheets and short structured dialog are quick to administer and easy to replicate across studies and should be tested in larger samples.

Setting budgets and priorities at state health agencies.

CONTEXT: State health departments across the country are responsible for assuring and improving the health of the public, and yet financial constraints grow only more acute, and resource allocation decisions become even more challenging. Little empirical evidence exists regarding how officials working in state health departments make these tough allocation decisions. DESIGN: Through a mixed-methods process, we attempted to address this gap in knowledge and characterize issues of resource allocation at state health agencies (SHAs). First, we conducted 45 semistructured interviews across 6 states. Next, a Web-based survey was sent to 355 public health leaders within all states and District of Columbia. In total, 207 leaders responded to the survey (66% response rate). PARTICIPANTS: Leaders of SHAs. RESULTS: The data suggest that state public health leaders are highly consultative internally while making resource allocation decisions, but they also frequently engage with the governor's office and the legislature-much more so at the executive level than at the division director level. Respondents reported that increasing and decreasing funding for certain activities occur frequently and have a moderate impact on the agency or division budget. Agencies continue to "thin the soup," or prefer cutting broadly to cutting deeply. CONCLUSIONS: Public health leaders report facing significant tradeoffs in the course of priority-setting. The authorizing environment continues to force public health leaders to make challenging tradeoffs between unmet need and political considerations, and among vulnerable groups.

Ethics and obesity prevention: ethical considerations in 3 approaches to reducing consumption of sugar-sweetened beverages.

Obesity and overweight prevalence soared to unprecedented levels in the United States, with 1 in 3 adults and 1 in 6 children currently categorized as obese. Although many approaches have been taken to encourage individual behavior change, policies increasingly attempt to modify environments to have a more positive influence on individuals' food and drink choices. Several policy proposals target sugar-sweetened beverages (SSBs), consumption of which has become the largest contributor to Americans' caloric intake. Yet proposals have been criticized for unduly inhibiting choice, being overly paternalistic, and stigmatizing low-income populations. We explored the ethical acceptability of 3 approaches to reduce SSB consumption: restricting sale of SSBs in public schools, levying significant taxes on SSBs, and prohibiting the use of Supplemental Nutrition and Assistance Program (formerly food stamps) benefits for SSB purchases.

Budget- and priority-setting criteria at state health agencies in times of austerity: a mixed-methods study.

OBJECTIVES: We examined critical budget and priority criteria for state health agencies to identify likely decision-making factors, pressures, and opportunities in times of austerity. METHODS: We have presented findings from a 2-stage, mixed-methods study with state public health leaders regarding public health budget- and priority-setting processes. In stage 1, we conducted hour-long interviews in 2011 with 45 health agency executive and division or bureau leaders from 6 states. Stage 2 was an online survey of 207 executive and division or bureau leaders from all state health agencies (66% response rate). RESULTS: Respondents identified 5 key criteria: whether a program was viewed as "mission critical," the seriousness of the consequences of not funding the program, financing considerations, external directives and mandates, and the magnitude of the problem the program addressed. CONCLUSIONS: We have presented empirical findings on criteria used in state health agency budgetary decision-making. These criteria suggested a focus and interest on core public health and the largest public health problems with the most serious ramifications.

The value of unhealthy eating and the ethics of healthy eating policies.

Unhealthy eating can have value for individuals and groups, even while it has disvalue in virtue of being unhealthy. In this paper, we discuss some ways in which unhealthy eating has value and draw out implications for the ethics of policies limiting access to unhealthy food. Discussing the value and disvalue of unhealthy eating helps identify opportunities for reducing unhealthy eating that has little value, and helps identify opportunities for eliminating trade-offs between health and other values by making unhealthy food experiences healthier without eliminating their value. It also helps us think through when it is ethically acceptable, and when it might be ethically unacceptable, to limit valuable experience in order to promote health. Our discussion of the value and disvalue of eating is offered here as a necessary supplement to the familiar discussion of paternalism, autonomous choice, and public policy.

Tradeoffs in resource allocation at state health agencies.

BACKGROUND: Priority setting is at the core of resource allocation. In recent years, priority setting in public health has occurred in the context of a difficult authorizing environment, one in which politicians have shown increasing interest in reducing the footprint of government, even during times of increased demand for social services. In this context of austerity, tradeoffs abound. These tradeoffs may occur not only within a single programmatic area in public health (e.g., cutting an infant mortality program vs a "Children With Special Health Care Needs" program) but also at a broader, more abstract level (e.g., favoring programs that are relatively more efficient for one population vs less efficient for programs serving a population in greater need of services). OBJECTIVES: This project was undertaken to provide more insight into tradeoffs within state health agencies with regard to what types of tradeoffs exist and how often they occur. METHODS: To characterize these tradeoffs, we engaged in a mixed-methods project where we first conducted 45 semistructured interviews with public health leaders across 6 state health agencies. Tradeoffs were elicited through open-ended questions and probes and qualitatively coded and analyzed. Next, we conducted a national survey across all state health agencies, receiving 207 responses (66% response rate). Survey respondents were asked to rate how frequently they encountered particular tradeoffs and how difficult they were to resolve. RESULTS: The most frequently encountered tradeoffs were "insufficient funding for a program versus no funding for a program" (84% rating as frequently/very frequently encountered) and prioritizing "current versus future need" (80% rating as frequently/very frequently). More than 50% of respondents said that they encountered 7 of the 11 tradeoffs frequently or very frequently and found 10 of the 11 difficult or very difficult to resolve. Forty-two percent of respondents rated "services for younger groups versus services for older groups" as difficult/very difficult to resolve.

Ethics and informed consent for comparative effectiveness research with prospective electronic clinical data.

BACKGROUND: Electronic clinical data (ECD) will increasingly serve as an important source of information for comparative effectiveness research (CER). Although many retrospective studies have relied on ECD, new study designs propose using ECD for prospective CER. These designs have great potential but they also raise important ethics questions. AIMS: Drawing on an ethics framework for learning health care systems, we identify morally relevant features of prospective CER-ECD studies by examining 1 case of an observational study and a second of a pragmatic, randomized trial. We focus only on questions of consent and assume research has been subject to appropriate ethics review and oversight. RESULTS AND CONCLUSIONS: We conclude that a CER-ECD observational study that imposes no or minimal additional risk to or burden on patients may proceed ethically without express informed consent from participants in settings where: (a) patients are regularly informed of the health care institution's commitment to learning through the integration of research and practice; and (b) there are appropriate protections for patients' rights and interests. In addition, where (a) and (b) apply, some pragmatic, randomized trials that similarly impose no or minimal additional risk to or burden on patients may also proceed ethically without express consent, when certain additional conditions are satisfied, including: (c) the trial does not negatively affect patients' prospects for good clinical outcomes; (d) physicians have the option of using an intervention other than the one assigned if they believe doing so is important for a particular patient; and (e) the trial does not engage preferences or values that are meaningful to patients.

Evaluating institutional capacity for research ethics in Africa: a case study from Botswana.

BACKGROUND: The increase in the volume of research conducted in Low and Middle Income Countries (LMIC), has brought a renewed international focus on processes for ethical conduct of research. Several programs have been initiated to strengthen the capacity for research ethics in LMIC. However, most such programs focus on individual training or development of ethics review committees. The objective of this paper is to present an approach to institutional capacity assessment in research ethics and application of this approach in the form of a case study from an institution in Africa. METHODS: We adapted the Octagon model originally used by the Swedish International Development Cooperation Agency to assess an organization along eight domains in research ethics: basic values and identity; structure and organization; ability to carry out activities; relevance of activities to stated goals; capacity of staff and management; administrative, financing and accounting systems; its relations with target groups; and the national context. We used a mixed methods approach to collect empirical data at the University of Botswana from March to December 2010. RESULTS: The overall shape of the external evaluation Octagon suggests that strengths of the University of Botswana are in the areas of structure, relevance, production and identity; while the university still needs more work in the areas of systems of finance, target groups, and environment. The Octagons also show the similarities and discrepancies between the 'external' and 'internal' evaluations and provide an opportunity for exploration of these different assessments. For example, the discrepant score for 'identity' between internal and external evaluations allows for an exploration of what constitutes a strong identity for research ethics at the University of Botswana and how it can be strengthened. CONCLUSIONS: There is a general lack of frameworks for evaluating research ethics capacity in LMICs. We presented an approach that stresses evaluation from both internal and external perspectives. This case study highlights the university's rapid progress in developing research ethics capacity and points to some notable areas for improvement. We believe that such an empirically-driven and participatory assessment allows a more holistic measurement and promotion of institutional capacity strengthening for research ethics in LMICs.

Ethics of Adaptive Designs for Randomized Controlled Trials.

Over recent decades, adaptive trial designs have been used more and more often for clinical trials, including randomized controlled trials (RCTs). This rise in the use of adaptive RCTs has been accompanied by debates about whether such trials offer ethical and methodological advantages over traditional, fixed RCTs. This study examined how experts on clinical trial methods and ethics believe that adaptive RCTs, compared to fixed ones, affect the ethical character of clinical research. We conducted in-depth interviews with 17 researchers from bioethics, epidemiology, biostatistics, and/or medical backgrounds. While about half believed that adaptive trials are more complex and may thus threaten autonomy, these respondents also expressed that this challenge is not insurmountable. Most respondents expressed that efficiency and potential for participant benefit were the main justifications for adaptive trials. There was tension about whether adaptive randomization in response to increasing information disrupts clinical equipoise, with some respondents insisting that uncertainty still exists and therefore clinical equipoise is not disrupted. These findings suggest that further discussion is needed to increase the awareness and utility of these study designs.

Towards achieving transnational research partnership equity: lessons from implementing adaptive platform trials in low- and middle-income countries.

Background: Use of adaptive clinical trials, particularly adaptive platform trials, has grown exponentially in response to the coronavirus disease (COVID-19) pandemic. Implementation of these trials in low- and middle-income countries (LMICs) has been fostered through the formation or modification of transnational research partnerships, typically between research groups from LMICs and high-income countries (HICs). While these partnerships are important to promote collaboration and overcome the structural and economic disadvantages faced by LMIC health researchers, it is critical to focus attention on the multiple dimensions of partnership equity. Methods: Based on informal literature reviews and a meeting with leaders of one of the multinational COVID-19 adaptive platform trials, we describe some important considerations about research partnership equity in this context. Results: We organize these considerations into eight thematic categories: 1) epistemic structures, 2) funding, 3) ethics oversight, 4) regulatory oversight, 5) leadership, 6) post-trial access to interventions, data, and specimens, 7) knowledge translation and dissemination, and 8) research capacity strengthening and maintenance. Within each category we review normative claims that support its relevance to research partnership equity followed by discussion of how adaptive platform trials highlight new dimensions, considerations, or challenges. Conclusion: In aggregate, these observations provide insight into procedural and substantive equity-building measures within transnational global health research partnerships more broadly.