Implied Claims in Drug Advertising: A Review of Recent Literature and Regulatory Actions.

Federal agencies and self-regulatory bodies help to ensure prescription and nonprescription drug promotion contains accurate information; however, false or misleading claims may cause people to have inaccurate perceptions of a drug and inhibit their ability to make informed decisions. We conducted a systematic review assessing evidence from 2012-2021 on how consumers and healthcare providers (HCPs) interpret claims made indirectly or through inference (implied or implicit claims) as well as synthesizing prescription and nonprescription drug advertising claims that have been the subject of regulatory actions from 2017-2021. Our search identified 16 studies from the peer-reviewed literature and 26 letters or case reports issued by the Food and Drug Administration (FDA) or National Advertising Division (NAD). Results from peer-reviewed studies suggest that implied claims can result in inferences that may not be warranted by the material facts about the drug. Perceptions of a drug's efficacy and, to a lesser extent, risk, are influenced by implied and explicitly false claims in prescription drug promotion. Claims related to implied superiority and overstatement of efficacy were the most prevalent claims flagged for review and examined in the literature. These types of claims were also the subject of many of the compliance actions by the FDA and case reports from the NAD. More research is needed to understand how people interpret varying types of implied claims and the impact of such claims on key outcomes. From a policy standpoint, understanding how people interpret implied claims can inform how the FDA approaches these claims in the marketplace.

Patient Understanding of Oncology Clinical Trial Endpoints in Direct-to-Consumer Television Advertising.

BACKGROUND: This study examined how people interpret overall survival (OS), overall response rate (ORR), and progression-free survival (PFS) endpoints in the context of direct-to-consumer television ads. Although there is little research on this topic, initial evidence suggests that people can misinterpret these endpoints. We hypothesized that understanding of ORR and PFS would be improved by adding a disclosure ("We currently do not know if [Drug] helps patients live longer") to ORR and PFS claims. METHODS: We conducted 2 online studies with US adults examining television ads for fictional prescription drugs indicated to treat lung cancer (N = 385) or multiple myeloma (N = 406). The ads included claims about OS, ORR with and without a disclosure, or PFS with and without a disclosure. In each experiment, we randomized participants to view 1 of 5 versions of a television ad. After viewing the ad twice, participants completed a questionnaire that measured understanding, perceptions, and other outcomes. RESULTS: In both studies, participants correctly differentiated between OS, ORR, and PFS via open-ended responses; however, participants in the PFS conditions (versus ORR conditions) were more likely to make incorrect inferences about OS. Supporting the hypothesis, adding a disclosure made expectations around living longer and quality-of-life improvements more accurate. CONCLUSION: Disclosures could help reduce the extent to which people misinterpret endpoints like ORR and PFS. More research is needed to establish best-practice recommendations for using disclosures to improve patient understanding of drug efficacy without changing their perception of the drug in unintended ways.

Physician Perceptions of the FDA's Breakthrough Therapy Designation: An Update.

The US Food and Drug Administration developed the Breakthrough Therapy designation to expedite the development and review of drugs that show a clear advantage over available therapy for serious conditions. Prior research has shown that physicians tend to misunderstand that a drug may receive a Breakthrough Therapy designation based on preliminary clinical evidence (eg, effect on a surrogate endpoint or intermediate clinical endpoint that is likely to predict clinical benefit). The objective of this article is to examine whether physicians' familiarity with and interpretation of the Breakthrough Therapy designation have changed since a survey on the topic was published in 2016. We replicated three of the questions in that study and explored beliefs that a Breakthrough Therapy designation automatically qualifies a drug for accelerated approval. We also draw comparisons by specialization (oncologists vs. primary care physicians). In general, physicians remain more likely than not to misunderstand the Breakthrough Therapy designation.

Using a Patient Portal to Increase Enrollment in a Newborn Screening Research Study: Observational Study.

BACKGROUND: Many research studies fail to enroll enough research participants. Patient-facing electronic health record applications, known as patient portals, may be used to send research invitations to eligible patients. OBJECTIVE: The first aim was to determine if receipt of a patient portal research recruitment invitation was associated with enrollment in a large ongoing study of newborns (Early Check). The second aim was to determine if there were differences in opening the patient portal research recruitment invitation and study enrollment by race and ethnicity, age, or rural/urban home address. METHODS: We used a computable phenotype and queried the health care system's clinical data warehouse to identify women whose newborns would likely be eligible. Research recruitment invitations were sent through the women's patient portals. We conducted logistic regressions to test whether women enrolled their newborns after receipt of a patient portal invitation and whether there were differences by race and ethnicity, age, and rural/urban home address. RESULTS: Research recruitment invitations were sent to 4510 women not yet enrolled through their patient portals between November 22, 2019, through March 5, 2020. Among women who received a patient portal invitation, 3.6% (161/4510) enrolled their newborns within 27 days. The odds of enrolling among women who opened the invitation was nearly 9 times the odds of enrolling among women who did not open their invitation (SE 3.24, OR 8.86, 95% CI 4.33-18.13; P<.001). On average, it took 3.92 days for women to enroll their newborn in the study, with 64% (97/161) enrolling their newborn within 1 day of opening the invitation. There were disparities by race and urbanicity in enrollment in the study after receipt of a patient portal research invitation but not by age. Black women were less likely to enroll their newborns than White women (SE 0.09, OR 0.29, 95% CI 0.16-0.55; P<.001), and women in urban zip codes were more likely to enroll their newborns than women in rural zip codes (SE 0.97, OR 3.03, 95% CI 1.62-5.67; P=.001). Black women (SE 0.05, OR 0.67, 95% CI 0.57-0.78; P<.001) and Hispanic women (SE 0.07, OR 0.73, 95% CI 0.60-0.89; P=.002) were less likely to open the research invitation compared to White women. CONCLUSIONS: Patient portals are an effective way to recruit participants for research studies, but there are substantial racial and ethnic disparities and disparities by urban/rural status in the use of patient portals, the opening of a patient portal invitation, and enrollment in the study. TRIAL REGISTRATION: ClinicalTrials.gov NCT03655223; https://clinicaltrials.gov/ct2/show/NCT03655223.

Detecting and Reporting Deceptive Prescription Drug Promotion: Differences Across Consumer and Physician Audiences and by Number and Type of Deceptive Claims and Tactics.

The U.S. Food and Drug Administration's (FDA) Bad Ad program provides an avenue for healthcare providers to report false or misleading prescription drug promotion. Yet, whether healthcare providers can detect such promotion, and whether they believe it should be reported to FDA, remain open questions. Consumer audiences may also be capable of detecting such promotion and believe it should be reported, but even less is known about capability and belief in this population. Across two experiments using mock pharmaceutical websites, this research investigated capability to detect and inclination to report deceptive prescription drug promotion among a sample of primary care physicians and consumers. Study 1 varied the number of deceptive claims and tactics on a website for a chronic pain medication, operationalized as none, two, or five. Study 2 varied the type of deceptive content on a website for a weight loss medication, operationalized as none, implicit, or explicit. Findings reveal that, in line with expectations from FDA's Bad Ad program, physicians can detect deceptive promotion and tend to believe it should be reported. Consumers are also capable of detecting deceptive promotion and tend to believe it should be reported, but their capabilities and beliefs regarding reporting are generally lower.

Physician Interpretation of Data of Uncertain Clinical Utility in Oncology Prescription Drug Promotion.

BACKGROUND: Little is known about how physicians interpret data displays that depict preliminary or exploratory clinical data in physician-targeted sales aids for oncology drugs. Using three factorial experiments, we examined whether disclosures of data limitations and clinical uncertainty adequately communicate the limitations and practical utility of this type of data. SUBJECTS, MATERIALS, AND METHODS: The studies used a 2 (disclosure of data limitations: technical, nontechnical) × 2 (disclosure of clinical uncertainty: present, absent) + 1 (control: no disclosure) between-subjects experimental design to examine the impact of disclosures as they relate to presentations of preliminary or exploratory data in promotional communications for oncology products. In each experiment, we randomized oncologists and primary care physicians with oncology experience to view one version of a two-page sales aid. Following this exposure, physicians completed a web-based survey. The design was replicated in three concurrently conducted experiments using sales aids for different fictitious oncology drugs, each featuring one of three common data displays: a forest plot (n = 495), a Kaplan-Meier curve (n = 504), or a bar chart (n = 532). RESULTS: Results provide initial evidence that in some contexts disclosures can improve understanding of the clinical utility of certain information about a drug and the limitations of results presented in a data display. Disclosures can also temper perceptions of how much evidence is presented that supports a conclusion that the drug is an appropriate treatment. In terms of the language used in the disclosure of data limitations, physicians in all three experiments strongly preferred the nontechnical disclosures. CONCLUSION: The findings from the three experiments in this study suggest that disclosures have the potential to increase relevant knowledge, but more research is needed to establish best practice recommendations for using disclosures to convey contextual information relevant for interpreting data displays in promotional communications. IMPLICATIONS FOR PRACTICE: This article reports the results from three large, online experimental studies that address a growing concern that drug companies often share favorable clinical trial results with physicians in promotional materials that lack important context for physicians to interpret the data. This series of studies investigates whether strategic use of two types of disclosures (disclosure of data limitations and a disclosure of clinical uncertainty) improves understanding and reduces misinterpretations among physicians. The results from these studies help identify communication factors that impact how physicians critically appraise preliminary or exploratory clinical trial data to inform policy and regulatory efforts.

Patients' and caregivers' maximum acceptable risk of death for non-curative gene therapy to treat Duchenne muscular dystrophy.

BACKGROUND: Gene therapy offers an etiologically targeted treatment for genetic disorders. Little is known about the acceptance of mortality risk among patients with progressive, fatal conditions. We assessed patients' and caregivers' maximum acceptable risk (MAR) of mortality for gene therapy when used to treat Duchenne muscular dystrophy (DMD). METHODS: The threshold technique was used to assess tolerance for mortality risks using a hypothetical vignette. Gene therapy was described as non-curative and resulting in a slowing of progression and with a 10-year benefit duration. MAR was analyzed using interval regression for gene therapy initiated "now"; in the last year of walking well; in the last year of being able to bring arms to mouth; and in newborns (for caregivers only). RESULTS: Two hundred eighty-five caregivers and 35 patients reported the greatest MAR for gene therapy initiated in last year of being able to lift arms (mean MAR 6.3%), followed by last year of walking well (mean MAR 4.4%), when used "now" (mean MAR 3.5%), and when used in the newborn period (mean MAR 2.1%, caregivers only). About 35% would accept ≥200/2000 risk in the last year of being able to lift arms. Non-ambulatory status predicted accepting 1.8 additional points in MAR "now" compared with ambulatory status (p = 0.010). Respondent type (caregiver or patient) did not predict MAR. CONCLUSION: In this first quantitative study to assess MAR associated with first-generation DMD gene therapy, we find relatively high tolerance for mortality risk in response to a non-curative treatment scenario. Risk tolerance increased with disease progression. Patients and caregivers did not have significantly different MAR. These results have implications for protocol development and shared decision making.

A behavior-theoretic evaluation of values clarification on parental beliefs and intentions toward genomic sequencing for newborns.

Decision aids commonly include values clarification exercises to help people consider which aspects of a choice matter most to them, and to help them make decisions that are congruent with their personal values and preferences. Using a randomized online experiment, we examined the influence of values clarification on parental beliefs and intentions about having genomic sequencing for newborns. We recruited 1186 women and men ages 18-44 who were pregnant or whose partner was pregnant or planning to become pregnant in the next two years. Participants (N = 1000) completed one of two versions of an online decision aid developed as part of a larger project examining the technical, clinical, and social aspects of using exome sequencing to screen newborns for rare genetic conditions. The education-only version provided information about using genomic sequencing to screen newborns for medically treatable conditions. The education-plus-values-clarification version included the same information, along with a values clarification exercise in which participants classified as important or unimportant five reasons in support of having and five reasons against having their newborn undergo genomic sequencing. We conducted partial correlations, regression analysis, and MANCOVAs with sex, health literacy, and experience with genetic testing as covariates. Participants who completed the decision aid with the values clarification exercise agreed less strongly with four of the five statements against sequencing compared to participants who viewed the education-only decision aid. The groups did not differ on agreement with reasons in support of sequencing. Agreement with four of five reasons against genomic sequencing was negatively associated with intentions to have their newborn sequenced, whereas agreement with all five reasons in support of sequencing were positively associated with intentions.

Experimental evidence of consumer and physician detection and rejection of misleading prescription drug website content.

BACKGROUND: Consumers and primary care physicians (PCPs) sometimes encounter deceptive promotional claims about prescription drugs. Whether consumers and PCPs can detect deceptive claims or whether those claims negatively affect medical decision making, however, remain important, unanswered research questions. OBJECTIVES: This article explores (1) the ability of consumers and PCPs to identify deceptive prescription drug promotion at various levels of deception, (2) the influence of such tactics on obstructing risk recognition, and (3) whether perceived deception mediates relationships between exposure to deceptive tactics and various outcomes (including false-claim acceptance, attitudes, information-seeking intentions, and interest toward the promoted drug). METHODS: Two experiments-1 with consumers (N = 366) and 1 with PCPs (N = 378)-were conducted to determine whether participant exposure to deceptive prescription drug website content corresponds to detection and acceptance (or rejection) of claims and tactics. In each experiment, the number of deceptive claims and tactics on a consumer- or PCP-targeted website for a fictitious chronic pain medication were varied, in a 1 × 3 (none, fewer, more) between-subjects design. RESULTS: Among consumers, exposure to more deceptive claims or tactics did not increase suspicion about the veracity of the website (relative to fewer claims and tactics) and actually had a limited positive direct effect on false-claim acceptance and attitudes toward the drug. Among PCPs, a mediation effect existed such that exposure to more deceptive claims and tactics resulted in higher perceived website deceptiveness relative to those in the fewer deceptive claims condition, which, in turn, resulted in lower acceptance of deceptive claims and tactics, lower perceived drug effectiveness, more negative attitudes toward the drug, and lower interest and intentions. CONCLUSION: These experiments demonstrate potential differences between consumers and PCPs as well as implications for consumer and PCP vulnerability to website deception.

Outreach to new mothers through direct mail and email: recruitment in the Early Check research study.

Meeting recruitment targets for clinical trials and health research studies is a notable challenge. Unsuccessful efforts to recruit participants from traditionally underserved populations can limit who benefits from scientific discovery, thus perpetuating inequities in health outcomes and access to care. In this study, we evaluated direct mail and email outreach campaigns designed to recruit women who gave birth in North Carolina for a statewide research study offering expanded newborn screening for a panel of rare health conditions. Of the 54,887 women who gave birth in North Carolina from September 28, 2018, through March 19, 2019, and were eligible to be included on the study's contact lists, we had access to a mailing address for 97.9% and an email address for 6.3%. Rural women were less likely to have sufficient contact information available, but this amounted to less than a one percentage point difference by urbanicity. Native American women were less likely to have an email address on record; however, we did not find a similar disparity when recruitment using direct-mail letters and postcards was concerned. Although we sent letters and emails in roughly equal proportion by urbanicity and race/ethnicity, we found significant differences in enrollment across demographic subgroups. Controlling for race/ethnicity and urbanicity, we found that direct-mail letters and emails were effective recruitment methods. The enrollment rate among women who were sent a recruitment letter was 4.1%, and this rate increased to 5.0% among women who were also sent an email invitation. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Under-representation by traditionally underserved populations in clinical trials and health research is a challenge that may in part reflect inequitable opportunities to participate. WHAT QUESTION DID THIS STUDY ADDRESS? Are direct-mail and email outreach strategies effective for reaching and recruiting women from traditionally underserved and rural populations to participate in large-scale, population-based research? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Despite sending recruitment letters and email invitations in roughly equal proportion by urbanicity and race/ethnicity, women living in rural areas were less likely to enroll (2.8%) than women from urban areas (4.2%). Additionally, enrollment rates decreased as the probability that women were members of a racial or ethnic minority group increased. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Results from this study might encourage researchers to take a holistic and participant-centered view of barriers to study enrollment that may disproportionately affect underserved communities, including differences in willingness to participate, trust, and access to resources needed for uptake.

Preferences for Accessing Electronic Health Records for Research Purposes: Views of Parents Who Have a Child With a Known or Suspected Genetic Condition.

OBJECTIVES: The purpose of this study was to examine parental preferences for researchers accessing their child's electronic health record across 3 groups: those with a child with (1) a known genetic condition (fragile X syndrome FXS), (2) a suspected genetic condition (autism spectrum disorder [ASD]), and (3) no known genetic condition (typically developing). METHODS: After extensive formative work, a discrete choice experiment was designed consisting of 5 attributes, each with 2 or 3 levels, including (1) type of researcher, (2) the use of personally identifiable information, (3) the use of sensitive information, (4) personal importance of research, and (5) return of results. Stratified mixed logit and latent class conditional logit models were examined. RESULTS: Parents of children with FXS or ASD had relatively higher preferences for research conducted by nonprofits than parents of typically developing children. Parents of children with ASD also preferred research using non-identifiable and nonsensitive information. Parents of children with FXS or ASD also had preferences for research that was personally important and returned either summary or individual results. Although a few child and family characteristics were related to preferences, they did not overall define the subgroups of parents. CONCLUSIONS: Although electronic health record preference research has been conducted with the general public, this is the first study to examine the opinions of parents who have a child with a known or suspected genetic condition. These parents were open to studies using their child's electronic health record because they may have more to gain from this type of research.

Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project.

Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. We enrolled healthy newborns and children with metabolic diseases or hearing loss (106 participants total). ES confirmed the participant's underlying diagnosis in 15 out of 17 (88%) children with metabolic disorders and in 5 out of 28 (∼18%) children with hearing loss. We discovered actionable findings in four participants that would not have been detected by standard NBS. A subset of parents was eligible to receive additional information for their child about childhood-onset conditions with low or no clinical actionability, clinically actionable adult-onset conditions, and carrier status for autosomal-recessive conditions. We found pathogenic variants associated with hereditary breast and/or ovarian cancer in two children, a likely pathogenic variant in the gene associated with Lowe syndrome in one child, and an average of 1.8 reportable variants per child for carrier results. These results highlight the benefits and limitations of using genomic sequencing for NBS and the challenges of using such technology in future precision medicine approaches.

Values clarification and parental decision making about newborn genomic sequencing.

OBJECTIVE: Using an online decision aid developed to support parental decision making about newborn genomic sequencing, we tested whether adding a values clarification exercise to educational content would improve decision making outcomes and influence intention to pursue genomic sequencing. We also examined whether the effect of values clarification varied depending on one's health literacy level. METHOD: In an online experiment, women and men aged 18 to 44 who were either pregnant or had a pregnant partner, were currently trying to get pregnant, or were preparing for a pregnancy within the next 2 years were randomly assigned to complete either a decision aid with educational information about newborn genomic sequencing or a decision aid with the same educational information and a values clarification exercise. RESULTS: Of the 1,000 participants who completed the decision aid, those who completed the values clarification exercise reported less decision regret, F(1, 995) = 6.19, p = .01, and were clearer about their personal values, F(1, 995) = 6.39, p = .01. Moderation analyses revealed that the benefit of values clarification on decisional conflict was particularly evident among participants with lower health literacy, B = -3.94, SE = 1.67, t = -2.36, p = .018. There was not a significant moderation effect of health literacy and decision aid condition on decision regret. CONCLUSIONS: Adding a values clarification exercise to decision aids for parents making decisions about genomic sequencing may improve the decision-making experience and provide some benefit to individuals with lower health literacy. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Early Check: translational science at the intersection of public health and newborn screening.

BACKGROUND: Newborn screening (NBS) occupies a unique space at the intersection of translational science and public health. As the only truly population-based public health program in the United States, NBS offers the promise of making the successes of translational medicine available to every infant with a rare disorder that is difficult to diagnose clinically, but for which strong evidence indicates that presymptomatic treatment will substantially improve outcomes. Realistic NBS policy requires data, but rare disorders face a special challenge: Screening cannot be done without supportive data, but adequate data cannot be collected in the absence of large-scale screening. The magnitude and scale of research to provide this expanse of data require working with public health programs, but most do not have the resources or mandate to conduct research. METHODS: To address this gap, we have established Early Check, a research program in partnership with a state NBS program. Early Check provides the infrastructure needed to identify conditions for which there have been significant advances in treatment potential, but require a large-scale, population-based study to test benefits and risks, demonstrate feasibility, and inform NBS policy. DISCUSSION: Our goal is to prove the benefits of a program that can, when compared with current models, accelerate understanding of diseases and treatments, reduce the time needed to consider inclusion of appropriate conditions in the standard NBS panel, and accelerate future research on new NBS conditions, including clinical trials for investigational interventions. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT03655223 . Registered on August 31, 2018.

Priorities when deciding on participation in early-phase gene therapy trials for Duchenne muscular dystrophy: a best-worst scaling experiment in caregivers and adult patients.

PURPOSE: Several gene therapy trials for Duchenne muscular dystrophy initiated in 2018. Trial decision making is complicated by non-curative, time-limited benefits; the progressive, fatal course; and high unmet needs. Here, caregivers and patients prioritize factors influencing decision making regarding participation in early-phase gene therapy trials. METHODS: We conducted a best-worst scaling experiment among U.S. caregivers and adults with Duchenne (N = 274). Participants completed 11 choice sets, choosing features they cared about most and least when deciding whether to participate in a hypothetical gene therapy trial. We analyzed the data using sequential conditional logistic regression. RESULTS: Participants prioritized improved muscle function in trial decision making. Concerns about participation limiting later use of gene transfer and editing were also important, as were improved lung and heart function. Low risk of death fell near the middle. Participants cared least about muscle biopsies and potential for randomization to placebo. Adults with Duchenne and caregivers of non-ambulatory children significantly prioritized improved lung function compared to caregivers of ambulatory children. CONCLUSION: Our data demonstrate prioritization of anticipated benefits and opportunity costs relative to potential harms and procedures in gene therapy trial decision making. Such data inform protocol development, education and advocacy efforts, and informed consent.

Expert and lay perspectives on burden, risk, tolerability, and acceptability of clinical interventions for genetic disorders.

PURPOSE: The Clinical Genome Resource (ClinGen) Actionability Working Group (AWG) developed a semiquantitative scoring metric to rate clinical actionability of genetic disorders and associated genes in four domains: (1) severity of the outcome, (2) likelihood of the outcome, (3) effectiveness of the intervention to prevent/minimize the outcome, and (4) nature of the intervention with respect to burden, risk, tolerability, and acceptability to the patient. This study aimed to assess whether nature of the intervention scores assigned by AWG experts reflected lay perceptions of intervention burden, risk, tolerability, and acceptability given the subjectivity of this domain. METHODS: In July 2017, a general population sample of 1344 adults completed the study. Each participant was asked to read 1 of 24 plain language medical intervention synopses and answer questions related to its burden, risk, tolerability, and acceptability. We conducted three multilevel mixed model analyses predicting the perceived burden, perceived risk, and perceived overall nature of the intervention. RESULTS: As AWG nature of the intervention scores increased, lay perceptions of intervention burden and risk decreased, and perceptions of tolerability and acceptability increased. CONCLUSION: The findings show alignment between the ClinGen actionability scoring metric and lay perceptions of the nature of the intervention.

An Interrupted Time Series Evaluation of the Testing Makes Us Stronger HIV Campaign for Black Gay and Bisexual Men in the United States.

Black gay, bisexual, and other men who have sex with men (BMSM) are the subpopulation most disproportionately affected by HIV in the United States. Testing Makes Us Stronger (TMUS), a communication campaign designed to increase HIV testing rates among BMSM ages 18 to 44, was implemented in the United States from December 2011 through September 2015. We used interrupted time series analysis (ITSA) to compare pre- and post-campaign trends in monthly HIV testing events among the priority audience in six of the implementation cities from January 2011 through December 2014. In the 11 months prior to the launch of TMUS, HIV testing events among BMSM in the six campaign implementation cities decreased by nearly 35 tests per month (p = .021). After the introduction of TMUS, the number of HIV testing events among BMSM in the same cities increased by more than 6 tests per month (p = .002). ITSA represents a quasi-experimental technique for investigating campaign effects beyond underlying time trends when serial outcome data are available. Future evaluations can be further strengthened by incorporating a comparison group to account for the effects of history and maturation on pre- and post-campaign trends.

Evaluating parents' decisions about next-generation sequencing for their child in the NC NEXUS (North Carolina Newborn Exome Sequencing for Universal Screening) study: a randomized controlled trial protocol.

BACKGROUND: Using next-generation sequencing (NGS) in newborn screening (NBS) could expand the number of genetic conditions detected pre-symptomatically, simultaneously challenging current precedents, raising ethical concerns, and extending the role of parental decision-making in NBS. The NC NEXUS (Newborn Exome Sequencing for Universal Screening) study seeks to assess the technical possibilities and limitations of NGS-NBS, devise and evaluate a framework to convey various types of genetic information, and develop best practices for incorporating NGS-NBS into clinical care. The study is enrolling both a healthy cohort and a cohort diagnosed with known disorders identified through recent routine NBS. It uses a novel age-based metric to categorize a priori the large amount of data generated by NGS-NBS and interactive online decision aids to guide parental decision-making. Primary outcomes include: (1) assessment of NGS-NBS sensitivity, (2) decision regret, and (3) parental decision-making about NGS-NBS, and, for parents randomized to have the option of requesting them, additional findings (diagnosed and healthy cohorts). Secondary outcomes assess parents' reactions to the study and to decision-making. METHODS/DESIGN: Participants are parents and children in a well-child cohort recruited from a prenatal clinic and a diagnosed cohort recruited from pediatric clinics that treat children with disorders diagnosed through traditional NBS (goal of 200 children in each cohort). In phase 1, all parent participants use an online decision aid to decide whether to accept NGS-NBS for their child and provide consent for NGS-NBS. In phase 2, parents who consent to NGS-NBS are randomized to a decision arm or control arm (2:1 allocation) and learn their child's NGS-NBS results, which include conditions from standard (non-NGS) NBS plus other highly actionable childhood-onset conditions. Parents in the decision arm use a second decision aid to make decisions about additional results from their child's sequencing. In phase 3, decision arm participants learn additional results they have requested. Online questionnaires are administered at up to five time points. DISCUSSION: NC NEXUS will use a rigorous interdisciplinary approach designed to collect rich data to inform policy, practice, and future research. TRIAL REGISTRATION: clinicaltrials.gov, NCT02826694 . Registered on 11 July, 2016.

Parental preferences toward genomic sequencing for non-medically actionable conditions in children: a discrete-choice experiment.

PurposeApplication of whole-exome and whole-genome sequencing is likely to increase in clinical practice, public health contexts, and research. We investigated how parental preference for acquiring information from genome-scale testing is influenced by the characteristics of non-medically actionable genetic disorders in children, as well as whether the preferences differed by gender and between African-American and white respondents.MethodsWe conducted a Web-based discrete-choice experiment with 1,289 parents of young children. Participants completed "choice tasks" based on pairs of profiles describing sequencing results for hypothetical genetic disorders, selected the profile in each pair that they believed represented the information that would be more important to know, and answered questions that measured their level of distress.ResultsKnowing the likelihood that the disorder would develop given a true-positive test result was most important to parents. Parents showed greater interest in learning sequencing results for disease profiles with more severe manifestations. This was associated with greater distress. Differences by gender and race reflected small differences in magnitude, but not direction.ConclusionParents preferred to learn results about genetic disorders with more severe manifestations, even when this knowledge was associated with increased distress. These results may help clinicians support parental decision making by revealing which types of sequencing results parents are interested in learning.

An Evidence-Based, Community-Engaged Approach to Develop an Interactive Deliberation Tool for Pediatric Neuromuscular Trials.

Duchenne/Becker muscular dystrophy (DBMD) and spinal muscular atrophy (SMA) are rare neuromuscular disorders that present challenges to therapeutic and clinical trial decision making. We developed an interactive, evidence-based online tool designed to encourage thoughtful deliberation of the pros and cons of trial participation and to inform meaningful discussions with healthcare providers. Prior research demonstrates the importance of tool availability at the time each family is considering trial participation, which may be prior to the informed consent process. The tool is intended to be easily modified to other pediatric disease communities. Tool development was informed by prior qualitative research, literature reviews, and stakeholder input. Specific items were derived based on an online exploratory questionnaire of parents whose children participated in a trial for DBMD or SMA to understand motivations for participation. Parent participants in the exploratory survey reported strong impact of altruistic and individual benefit motivations and placed much greater emphasis on anticipated trial benefits than on harms when making participation decisions. We used this data to develop the evidence-based deliberation tool using a community-engaged approach. We initially targeted the tool for DBMD while using SMA survey data to evaluate ease of transition to that population. We conducted two iterative sets of activities to inform development and refinement of the tool: (1) community engagement of key stakeholders and (2) user experience testing. These activities suggest that the tool may increase deliberation and the weighing of benefits and harms. Ongoing evaluation will determine the acceptability and efficacy of this online intervention.