Evaluating ApoL1 Genetic Testing Policy Options for Transplant Centers: A Delphi Consensus Panel Project with Stakeholders.

BACKGROUND: Apolipoprotein L1 (ApoL1) variants G1 and G2 are associated with a higher risk of kidney disease. ApoL1 risk variants are predominantly seen in individuals with sub-Saharan African ancestry. In most transplant centers, potential organ donors are being selectively genetically tested for ApoL1 risk variants. Transplant programs have highly variable ApoL1 testing practices and need guidance on essential ApoL1 clinical policy questions. METHODS: We conducted a Delphi consensus panel focused on ApoL1 clinical policy questions, including who gets tested, who decides whether testing occurs, how test results are shared, who receives test results, and how test results are used. A total of 27 panelists across seven stakeholder groups participated: living kidney donors ( n =4), deceased donor family members ( n =3), recipients of a deceased donor kidney ( n =4), recipients of a living donor kidney ( n =4), nephrologists ( n =4), transplant surgeons ( n =4), and genetic counselors ( n =4). Nineteen panelists (70%) identified as Black. The Delphi panel process involved two rounds of educational webinars and three rounds of surveys administered to panelists, who were asked to indicate whether they support, could live with, or oppose each policy option. RESULTS: The panel reached consensus on one or more acceptable policy options for each clinical policy question; panelists supported 18 policy options and opposed 15. Key elements of consensus include the following: ask potential donors about African ancestry rather than race; make testing decisions only after discussion with donors; encourage disclosure of test results to blood relatives and organ recipients but do not require it; use test results to inform decision making, but never for unilateral decisions by transplant programs. CONCLUSIONS: The panel generally supported policy options involving discussion and shared decision making among patients, donors, and family stakeholders. There was general opposition to unilateral decision making and prohibiting donation altogether.

Principal Investigators' Priorities and Perceived Barriers and Facilitators When Making Decisions About Conducting Essential Research in the COVID-19 Pandemic.

At the onset of the COVID-19 pandemic in the United States, stay-at-home orders disrupted normal research operations. Principal investigators (PIs) had to make decisions about conducting and staffing essential research under unprecedented, rapidly changing conditions. These decisions also had to be made amid other substantial work and life stressors, like pressures to be productive and staying healthy. Using survey methods, we asked PIs funded by the National Institutes of Health and the National Science Foundation (N = 930) to rate how they prioritized different considerations, such as personal risks, risks to research personnel, and career consequences, when making decisions. They also reported how difficult they found these choices and associated symptoms of stress. Using a checklist, PIs indicated those factors in their research environments that made their decisions easier (i.e., facilitators) or more difficult (i.e., barriers) to make. Finally, PIs also indicated how satisfied they were with their decisions and management of research during the disruption. Descriptive statistics summarize PIs' responses and inferential tests explore whether responses varied by academic rank or gender. PIs overall reported prioritizing the well-being and perspectives of research personnel, and they perceived more facilitators than barriers. Early-career faculty, however, rated concerns about their careers and productivity as higher priorities compared to their senior counterparts. Early-career faculty also perceived greater difficulty and stress, more barriers, fewer facilitators, and had less satisfaction with their decisions. Women rated several interpersonal concerns about their research personnel more highly than men and reported greater stress. The experience and perceptions of researchers during the COVID-19 pandemic can inform policies and practices when planning for future crises and recovering from the pandemic.

Barriers to Using Legally Authorized Representatives in Clinical Research with Older Adults.

Background: Older adults are at increased risk of cognitive impairments including Alzheimer's disease dementia. Legally authorized representatives (LARs) can provide informed consent when a participant is no longer able to, but little is known about barriers to incorporating them in research. Objective: Explore reasons for not asking and documenting participant decisions to appoint LARs among researchers conducting clinical intervention trials studying older adults or individuals with cognitive impairments. Methods: Mixed method design consisting of a survey (N = 1,284) and qualitative interviews (N = 40) regarding barriers to incorporating LARs. Participants were principal investigators and clinical research coordinators. Results: 37% (N = 469) had not asked and documented participant decisions about appointing LARs in the prior year. They had significantly lower confidence in resources available to incorporate LARs and lower positive attitudes compared to their counterparts who had done so. The majority (83%) had no trials studying individuals with cognitive impairments and reported LARs were not applicable. A minority (17%) had at least one trial studying individuals with cognitive impairments and reported being unaware of LARs. Qualitative findings indicate discomfort broaching a sensitive topic especially with individuals who are not yet impaired. Conclusion: Resources and education to increase awareness and knowledge of LARs are needed. Researchers studying older adults should, at minimum, have the knowledge and resources to incorporate LARs when necessary. Stigma and discomfort discussing LARs will need to be overcome, as early proactive discussions before a participant loses decisional capacity could enhance participant autonomy and facilitate recruitment and retention of older adults to research.

A randomized implementation trial to increase adoption of evidence-informed consent practices.

Introduction: Several evidence-informed consent practices (ECPs) have been shown to improve informed consent in clinical trials but are not routinely used. These include optimizing consent formatting, using plain language, using validated instruments to assess understanding, and involving legally authorized representatives when appropriate. We hypothesized that participants receiving an implementation science toolkit and a social media push would have increased adoption of ECPs and other outcomes. Methods: We conducted a 1-year trial with clinical research professionals in the USA (n = 1284) who have trials open to older adults or focus on Alzheimer's disease. We randomized participants to receive information on ECPs via receiving a toolkit with a social media push (intervention) or receiving an online learning module (active control). Participants completed a baseline survey and a follow-up survey after 1 year. A subset of participants was interviewed (n = 43). Results: Participants who engaged more with the toolkit were more likely to have tried to implement an ECP during the trial than participants less engaged with the toolkit or the active control group. However, there were no significant differences in the adoption of ECPs, intention to adopt, or positive attitudes. Participants reported the toolkit and social media push were satisfactory, and participating increased their awareness of ECPs. However, they reported lacking the time needed to engage with the toolkit more fully. Conclusions: Using an implementation science approach to increase the use of ECPs was only modestly successful. Data suggest that having institutional review boards recommend or require ECPs may be an effective way to increase their use.

What Can State Medical Boards Do to Effectively Address Serious Ethical Violations?

State Medical Boards (SMBs) can take severe disciplinary actions (e.g., license revocation or suspension) against physicians who commit egregious wrongdoing in order to protect the public. However, there is noteworthy variability in the extent to which SMBs impose severe disciplinary action. In this manuscript, we present and synthesize a subset of 11 recommendations based on findings from our team's larger consensus-building project that identified a list of 56 policies and legal provisions SMBs can use to better protect patients from egregious wrongdoing by physicians.

Ethical, regulatory, and practical barriers to COVID-19 research: A stakeholder-informed inventory of concerns.

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused death and economic injury around the globe. The urgent need for COVID-19 research created new ethical, regulatory, and practical challenges. The next public health emergency could be worse than COVID-19. We must learn about these challenges from the experiences of researchers and Research Ethics Committee professionals responsible for these COVID-19 studies to prepare for the next emergency. MATERIALS AND METHODS: We conducted an online survey to identify the ethical, oversight, and regulatory challenges of conducting COVID-19 research during the early pandemic, and proposed solutions for overcoming these barriers. Using criterion-based, convenience sampling, we invited researchers who proposed or conducted COVID-19 research to complete an anonymous, online survey about their experiences. We administered a separate but related survey to Institutional Review Board (IRB) professionals who reviewed COVID-19 research studies. The surveys included open-ended and demographic items. We performed inductive content analysis on responses to open-ended survey questions. RESULTS: IRB professionals (n = 143) and researchers (n = 211) described 19 types of barriers to COVID-19 research, related to 5 overarching categories: policy and regulatory, biases and misperceptions, institutional and inter-institutional conflicts, risks of harm, and pressure of the pandemic. Researchers and IRB professionals described 8 categories of adaptations and solutions to these challenges: enacting technological solutions; developing protocol-based solutions; disposition and team management; establishing and communicating appropriate standards; national guidance and leadership; maintaining high standards; prioritizing studies before IRB review; and identifying and incorporating experts. DISCUSSION AND CONCLUSIONS: This inventory of challenges represents ongoing barriers to studying the current pandemic, and they represent a risk to research during future public health emergencies. Delays in studies of a pandemic during a pandemic threatens the health and safety of the public. We urge the development of a national working group to address these issues before the next public health emergency arises.

Understanding the Use of Optimal Formatting and Plain Language When Presenting Key Information in Clinical Trials.

Recent revisions to the Common Rule require that consent documents begin with a focused presentation of the study's key information that is organized to facilitate understanding. We surveyed 1,284 researchers working with older adults or individuals with Alzheimer's disease, supplemented with 60 qualitative interviews, to understand current use and barriers to using evidence-based formatting and plain language in key information. Researchers reported using formatting in 42% of their key information sections, and plain language in 63% of their key information sections. Perceived barriers included lack of knowledge, Institutional Review Board, other members of their team, and the burden associated with implementation. Education and training are required to increase adoption of the practices.

Perceived barriers to assessing understanding and appreciation of informed consent in clinical trials: A mixed-method study.

INTRODUCTION: Participants and research professionals often overestimate how well participants understand and appreciate consent information for clinical trials, and experts often vary in their determinations of participant's capacity to consent to research. Past research has developed and validated instruments designed to assess participant understanding and appreciation, but the frequency with which they are utilized is unknown. METHODS: We administered a survey to clinical researchers working with older adults or those at risk of cognitive impairment (N = 1284), supplemented by qualitative interviews (N = 60). RESULTS: We found that using a validated assessment of consent is relatively uncommon, being used by only 44% of researchers who had an opportunity. Factors that predicted adoption of validated assessments included not seeing the study sponsor as a barrier, positive attitudes toward assessments, and being confident that they had the resources needed to implement an assessment. The perceived barriers to adopting validated assessments of consent included lack of awareness, lack of knowledge, being unsure of how to administer such an assessment, and the burden associated with implementing this practice. CONCLUSIONS: Increasing the use of validated assessments of consent will require educating researchers on the practice and emphasizing very practical assessments, and may require Institutional Review Boards (IRBs) or study sponsors to champion the use of assessments.

Attitudes toward genomics and precision medicine.

PURPOSE: This paper reports on a novel measure, attitudes toward genomics and precision medicine (AGPM), which evaluates attitudes toward activities such as genetic testing, collecting information on lifestyle, and genome editing - activities necessary to achieve the goals of precision medicine. DISCUSSION: The AGPM will be useful for researchers who want to explore attitudes toward genomics and precision medicine. The association of concerns about precision medicine activities with demographic variables such as religion and politics, as well as higher levels of education, suggests that further education on genomic and precision activities alone is unlikely to shift AGPM scores significantly. METHODS: We wrote items to represent psychological and health benefits of precision medicine activities, and concerns about privacy, social justice, harm to embryos, and interfering with nature. We validated the measure through factor analysis of its structure, and testing associations with trust in the health information system and demographic variables such as age, sex, education, and religion. RESULTS: The AGPM had excellent alpha reliability (.92) and demonstrated good convergent validity with existing measures. Variables most strongly associated with higher levels of concern with precision medicine activities included: regular religious practice, republican political leanings, and higher levels of education.

Research Participant Views regarding Qualitative Data Sharing.

We found no studies in the United States that explored research participants' perspectives about sharing their qualitative data. We present findings from interviews with 30 individuals who participated in sensitive qualitative studies to explore their understanding and concerns regarding qualitative data sharing. The vast majority supported sharing qualitative data so long as their data were deidentified and shared only among researchers. However, they raised concerns about confidentiality if the data were not adequately deidentified and about misuse by secondary users if data were shared beyond the research community. These concerns, though, did not deter them from participating in research. Notably, participants hoped their data would be shared and may have expected or assumed this was already happening. While many could not recollect details about data-sharing plans for studies in which they participated, they trusted researchers and institutions to appropriately handle data sharing. If individuals view data sharing as an extension or integral part of their participation in qualitative research, then researchers may have a stronger obligation to share qualitative data than previously thought. Guidelines and tools to assist researchers and institutional review board members in ethical and responsible qualitative data sharing are urgently needed.

Assessing clinical research coordinator knowledge of good clinical practice: An evaluation of the state of the art and a test validation study.

This paper describes the development and validation of a new 32-item test of knowledge of good clinical practice (GCP) administered to 625 clinical research coordinators. GCP training is mandated by study sponsors including the US National Institutes of Health. The effectiveness of training is rarely assessed, and the lack of validated tests is an obstacle to assessment. The GCP knowledge test was developed following evaluation of two existing widely used GCP tests to ensure it accurately reflects the content of current training. The final GCP knowledge test demonstrated good reliability (α = 0.69). It is a valid and reliable instrument for measuring knowledge of GCP. The test will be useful in assessing the effectiveness of GCP training programs as well as individuals' mastery of GCP content.

Are we ready to share qualitative research data? Knowledge and preparedness among qualitative researchers, IRB Members, and data repository curators.

Data sharing maximizes the value of data, which is time and resource intensive to collect. Major funding bodies in the United States (US), like the National Institutes of Health (NIH), require data sharing and researchers frequently share de-identified quantitative data. In contrast, qualitative data are rarely shared in the US but the increasing trend towards data sharing and open science suggest this may be required in future. Qualitative methods are often used to explore sensitive health topics raising unique ethical challenges regarding protecting confidentiality while maintaining enough contextual detail for secondary analyses. Here, we report findings from semi-structured in-depth interviews with 30 data repository curators, 30 qualitative researchers, and 30 IRB staff members to explore their experience and knowledge of QDS. Our findings indicate that all stakeholder groups lack preparedness for QDS. Researchers are the least knowledgeable and are often unfamiliar with the concept of sharing qualitative data in a repository. Curators are highly supportive of QDS, but not all have experienced curating qualitative data sets and indicated they would like guidance and standards specific to QDS. IRB members lack familiarity with QDS although they support it as long as proper legal and regulatory procedures are followed. IRB members and data curators are not prepared to advise researchers on legal and regulatory matters, potentially leaving researchers who have the least knowledge with no guidance. Ethical and productive QDS will require overcoming barriers, creating standards, and changing long held practices among all stakeholder groups.

How do clinical research coordinators learn Good Clinical Practice? A mixed-methods study of factors that predict uptake of knowledge.

BACKGROUND: Good Clinical Practice is an international standard for the design and conduct of clinical trials to ensure ethical and scientific integrity. Recent National Institutes of Health policy mandates Good Clinical Practice training for all investigators and staff involved in National Institutes of Health-funded clinical trials, yet approaches to Good Clinical Practice training vary widely. There are limited data on Good Clinical Practice knowledge among the clinical trial workforce and no evidence regarding effective methods to learn Good Clinical Practice. METHODS: We used an exploratory sequential mixed-methods design. We conducted 18 exploratory qualitative interviews with clinical research coordinators to help inform the development of the quantitative survey. We then administered a validated 32-item, multiple-choice test of Good Clinical Practice knowledge with a survey of work and training experiences to 625 clinical research coordinators at three academic medical centers in the United States. Variables that were significantly associated with Good Clinical Practice knowledge were entered into a multiple regression analysis to identify unique predictors of Good Clinical Practice knowledge. We controlled for verbal-numerical reasoning and learning orientation. RESULTS: During qualitative interviews, clinical research coordinators reported that formal Good Clinical Practice training had value but they simultaneously emphasized the importance of experience, day-to-day practice, and observing colleagues and mentors as essential to supplement formal training. In our quantitative survey, five variables predicted a total of 22% of variance in Good Clinical Practice knowledge scores: years of experience as a clinical research coordinator, working on diverse types of trials, supporting industry-funded trials, being certified in clinical research coordination, and aggregated hours of online and face-to-face training (in that order). CONCLUSION: The duration and richness of experience as a clinical research coordinator were the strongest predictors of Good Clinical Practice knowledge, a finding consistent with our exploratory qualitative interview results. Our findings suggest that formal online and face-to-face training has a minimal influence on Good Clinical Practice knowledge. The type of training-whether online or face to face-does not make a significant difference in Good Clinical Practice knowledge scores. Much of the variance in Good Clinical Practice knowledge remains unexplained, calling for further research in this area.

What Explains Associations of Researchers' Nation of Origin and Scores on a Measure of Professional Decision-Making? Exploring Key Variables and Interpretation of Scores.

Researchers encounter challenges that require making complex professional decisions. Strategies such as seeking help and anticipating consequences support decision-making in these situations. Existing evidence on a measure of professional decision-making in research (the PDR) that assesses the use of decision-making strategies revealed that NIH-funded researchers born outside of the U.S. tended to score below their U.S. counterparts. To examine potential explanations for this association, this study recruited 101 researchers born in the United States and 102 born internationally to complete the PDR and measures of basic personal values, values in scientific work, discrimination between the seriousness of rules in research, exposure to unprofessional research practices, and acculturation to American culture. Several variables were associated with PDR scores-discrimination between types of rules in research, exposure to unprofessional research practices, acculturation, and the basic personal values of power, security, and benevolence. However, only security, benevolence, acculturation, and rule discrimination were also associated with nation of origin. In multivariate models, the variance explained by these variables in accounting for the association of nation of origin and PDR scores was somewhat overlapping, thus, only security and benevolence remained as unique, statistically significant predictors. Thus, this study identified some important variables in the association of nation of origin and PDR, but more research is needed. In a secondary analysis to examine the "clinical significance" (the practical importance) of scores on the PDR, this study examined aggregated PDR score data from the present sample and past samples of investigators. This analysis identified scores that may suggest a concern versus those scores that may be interpreted as excellent, proficient, or marginal. Implications for training and mentoring, along with considerations for future research are discussed.

Development and Preliminary Validation of a New Measure of Values in Scientific Work.

In this paper we describe the development and initial psychometric evaluation of a new measure, the values in scientific work (VSW). This scale assesses the level of importance that investigators attach to different VSW. It taps a broad range of intrinsic, extrinsic, and social values that motivate the work of scientists, including values specific to scientific work (e.g., truth and integrity) and more classic work values (e.g., security and prestige) in the context of science. Notably, the values represented in this scale are relevant to scientists regardless of their career stage and research focus. We administered the VSW and a measure of global values to 203 NIH-funded investigators. Exploratory factor analyses suggest the delineation of eight VSW, including autonomy, research ethics, social impact, income, collaboration, innovation and growth, conserving relationships, and job security. These VSW showed predictable and distinct associations with global values. Implications of these findings for work on research integrity and scientific misconduct are discussed.

The Role of Culture and Acculturation in Researchers' Perceptions of Rules in Science.

Successfully navigating the norms of a society is a complex task that involves recognizing diverse kinds of rules as well as the relative weight attached to them. In the United States (U.S.), different kinds of rules-federal statutes and regulations, scientific norms, and professional ideals-guide the work of researchers. Penalties for violating these different kinds of rules and norms can range from the displeasure of peers to criminal sanctions. We proposed that it would be more difficult for researchers working in the U.S. who were born in other nations to distinguish the seriousness of violating rules across diverse domains. We administered a new measure, the evaluating rules in science task (ERST), to National Institutes of Health-funded investigators (101 born in the U.S. and 102 born outside of the U.S.). The ERST assessed perceptions of the seriousness of violating research regulations, norms, and ideals, and allowed us to calculate the degree to which researchers distinguished between the seriousness of each rule category. The ERST also assessed researchers' predictions of the seriousness that research integrity officers (RIOs) would assign to the rules. We compared researchers' predictions to the seriousness ratings of 112 RIOs working at U.S. research-intensive universities. U.S.-born researchers were significantly better at distinguishing between the seriousness of violating federal research regulations and violating ideals of science, and they were more accurate in their predictions of the views of RIOs. Acculturation to the U.S. moderated the effects of nationality on accuracy. We discuss the implications of these findings in terms of future research and education.

Exploring unnecessary invasive procedures in the United States: a retrospective mixed-methods analysis of cases from 2008-2016.

BACKGROUND: Unnecessary invasive procedures risk harming patients physically, emotionally, and financially. Very little is known about the factors that provide the motive, means, and opportunity (MMO) for unnecessary procedures. METHODS: This project used a mixed-methods design that involved five key steps: (1) systematically searching the literature to identify cases of unnecessary procedures reported from 2008 to 2016; (2) identifying all medical board, court, and news records on relevant cases; (3) coding all relevant records using a structured codebook of case characteristics; (4) analyzing each case using a MMO framework to develop a causal theory of the case; and (5) identifying typologies of cases through a two-step cluster analysis using variables hypothesized to be causally related to unnecessary procedures. RESULTS: Seventy-nine cases met inclusion criteria. The mean number of documents or sources examined for each case was 36.4. Unnecessary procedures were performed for at least five years in most cases (53.2%); 56.3% of the cases involved 30 or more patients, and 37.5% involved 100 or more patients. In nearly all cases the physician was male (96.2%) and working in private practice (92.4%); 57.0% of the physicians had an accomplice, 48.1% were 50 years of age or older, and 40.5% trained outside the U.S. The most common motives were financial gain (92.4%) and suspected antisocial personality (48.1%), followed by poor problem-solving or clinical skills (11.4%) and ambition (3.8%). The most common environmental factors that provided opportunity for unnecessary procedures included a lack of oversight (40.5%) or oversight failures (39.2%), a corrupt moral climate (26.6%), vulnerable patients (20.3%), and financial conflicts of interest (13.9%). CONCLUSIONS: Unnecessary procedures usually appear motivated by financial gain and occur in settings that have oversight problems. Preventive efforts should focus on early detection by peers and institutions, and decisive action by medical boards and federal prosecutors.

Making Professional Decisions in Research: Measurement and Key Predictors.

The professional decision-making in research (PDR) measure was administered to 400 National Institutes of Health (NIH)-funded and industry-funded investigators, along with measures of cynicism, moral disengagement, compliance disengagement, impulsivity, work stressors, knowledge of responsible conduct of research (RCR), and socially desirable response tendencies. Negative associations were found for the PDR and measures of cynicism, moral disengagement, and compliance disengagement, while positive associations were found for the PDR and RCR knowledge and positive urgency, an impulsivity subscale. PDR scores were not related to socially desirable responding, or to measures of work stressors and the remaining impulsivity subscales. In a multivariate logistic regression analysis, lower moral disengagement scores, higher RCR knowledge, and identifying the United States as one's nation of origin emerged as key predictors of stronger performance on the PDR. The implications of these findings for understanding the measurement of decision-making in research and future directions for research and RCR education are discussed.

Professional Decision-Making in Research (PDR): The Validity of a New Measure.

In this paper, we report on the development and validity of the Professional Decision-Making in Research (PDR) measure, a vignette-based test that examines decision-making strategies used by investigators when confronted with challenging situations in the context of empirical research. The PDR was administered online with a battery of validity measures to a group of NIH-funded researchers and research trainees who were diverse in terms of age, years of experience, types of research, and race. The PDR demonstrated adequate reliability (alpha = .84) and parallel form correlation (r = .70). As hypothesized, the PDR was significantly negatively correlated with narcissism, cynicism, moral disengagement, and compliance disengagement; it was not correlated with socially desirable responding. In regression analysis, the strongest predictors of higher PDR scores were low compliance disengagement, speaking English as a native language, conducting clinical research with human subjects, and low levels of narcissism. Given that the PDR was written at an eighth grade reading level to be suitable for use with English as a second language participants and that only one-fourth of items focused on clinical research, further research into the possible roles of culture and research ethics training across specialties is warranted. This initial validity study demonstrates the potential usefulness of the PDR as an educational outcome assessment measure and a research instrument for studies on professionalism and integrity in research.

A Mixed-Method Analysis of Reports on 100 Cases of Improper Prescribing of Controlled Substances.

Improper prescribing of controlled substances contributes to opioid addictions and deaths by overdose. Studies conducted to-date have largely lacked a theoretical framework and ignored the interaction of individual with environmental factors. We conducted a mixed-method analysis of published reports on 100 cases that occurred in the United States. An average of 17 reports (e.g., from medical boards) per case were coded for 38 dichotomous variables describing the physician, setting, patients, and investigation. A theory on how the case occurred was developed for each case. Explanatory typologies were developed and then validated through hierarchical cluster analysis. Most cases involved physicians who were male (88%), >40 years old (90%), non-board certified (63%), and in small private practices (97%); 54% of cases reported facts about the physician indicative of self-centered personality traits. Three explanatory typologies were validated. Increasing oversight provided by peers and trainees may help prevent improper prescribing of controlled substances.