Pragmatic Randomized Trials Without Standard Informed Consent?: A National Survey.
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ABSTRACT:
SUBMITTER: Nayak RK
PROVIDER: S-EPMC5573142 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
Publications
Pragmatic Randomized Trials Without Standard Informed Consent?: A National Survey.
Nayak Rahul K RK Wendler David D Miller Franklin G FG Kim Scott Y H SY
Annals of internal medicine 20150901 5
<h4>Background</h4>Significant debate surrounds the issue of whether written consent is necessary for pragmatic randomized, controlled trials (RCTs) with low risk.<h4>Objective</h4>To assess the U.S. public's views on alternatives to written consent for low-risk pragmatic RCTs.<h4>Design</h4>National experimental survey (2 × 2 factorial design) examining support for written consent versus general notification or verbal consent in 2 research scenarios.<h4>Setting</h4>Web-based survey conducted in ...[more]
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Project description:The requirement to obtain written informed consent may undermine the potential of pragmatic randomized clinical trials (pRCTs) to improve evidence-based care. This requirement could compromise trials statistical power or even force it to close them down prematurely. However, recent data from the U.S. and Spain suggest that a majority of the public endorses written consent for low-risk pRCTs. The present manuscript assesses whether this view is shared by patients.This was a cross-sectional, probability-based survey, with a 2 × 2 factorial design, assessing support for written informed consent versus verbal consent or general notification for two low-risk pRCTs in hypertension, one comparing 2 drugs with similar risk/benefit profiles and the other comparing the same drug being taken in the morning or at night. This web-based survey was conducted in May 2016. Two-thousand and eight adults who were representative of the Spanish population participated in the survey (response rate: 61%). Of these 2008 respondents, 338 indicated that they had been diagnosed with hypertension and were being treated with prescription medicines for this condition at the time of responding to the survey. The primary outcome measures were respondents' personal preference and recommendation to a research ethics committee regarding the use of written informed consent versus verbal consent or general notification.Overall, 74% of the 338 patient respondents endorsed written consent. In both scenarios, general notification received significantly more support (30.6%-44.7%) than verbal consent (13.3%-17.6%). 43% of respondents preferred and/or recommended general notification rather than written consent.As in the survey of the general public, more patients endorsed written consent than the alternative option. However, two factors suggest that a different approach to written consent should be investigated for low-risk pRCTs: a) a substantial minority of respondents supported general notification, b) data from the US have shown that most patients who prefer written consent are willing to forego it if obtaining written consent makes the trial too difficult to be conducted; and c) 2016 CIOMS guidelines endorse waivers of consent when the trial fulfills specific conditions. Surveys in other EU countries are needed to assess what patients believe towards pRCTs. If similar results to that reported in this study are found, it is foreseeable that with educational efforts, general notification could be an acceptable and widespread approach to the conduct of low-risk pRCTs.
| S-EPMC5604493 | biostudies-other
Project description:AimsPragmatic randomized clinical trials (pRCTs) collect data that have the potential to improve medical care significantly. However, these trials may be undermined by the requirement to obtain written informed consent, which can decrease accrual and increase selection bias. Recent data suggest that the majority of the US public endorses written consent for low-risk pRCTs. The present study was designed to assess whether this view is specific to the US.MethodsThe study took the form of a cross-sectional, probability-based survey, with a 2 × 2 factorial design, assessing support for written informed consent vs. verbal consent or general notification for two low-risk pRCTs in hypertension, one comparing two drugs with similar risk/benefit profiles and the other comparing the same drug being taken in the morning or at night. The primary outcome measures were respondents' personal preference and hypothetical recommendation to a research ethics committee regarding the use of written informed consent vs. the alternatives.ResultsA total of 2008 adults sampled from a probability-based online panel responded to the web-based survey conducted in May 2016 (response rate: 61%). Overall, 77% of respondents endorsed written consent. In both scenarios, the alternative of general notification received significantly more support (28.7-37.1%) than the alternative of verbal consent (12.7-14.0%) (P = 0.001). Forty per cent of respondents preferred and/or recommended general notification rather than written consent.ConclusionsThe results suggested that, rather than attempting to waive written consent, current pRCTs should focus on developing ways to implement written consent that provide sufficient information without undermining recruitment or increasing selection bias. The finding that around 40% of respondents endorsed general notification over written consent raises the possibility that, with educational efforts, the majority of Spaniards might accept general notification for low-risk pRCTs.
| S-EPMC5582372 | biostudies-literature
Project description:IntroductionEarly phase cancer clinical trials have become increasingly complicated in terms of patient selection and trial procedures-this is reflected in the increasing length of participant information sheets (PIS). Informed consent for early phase clinical trials has been contentious due to the potential ethical issues associated with performing experimental research on a terminally ill population which has exhausted standard treatment options. Empirical studies have demonstrated significant gaps in patient understanding regarding the nature and intent of these trials. This study aims to test whether enhanced informed consent for patient education can improve patient scores on a validated questionnaire testing clinical trial comprehension.Methods and analysisThis is a randomised controlled trial that will allocate patients who are eligible to participate in one of four investigator-initiated clinical trials at the Royal Marsden Drug Development Unit to either a standard arm or an experimental arm, stratified by age and educational level. The standard arm will involve the full length trial PIS, followed by electronic or paper administration of the Quality of Informed Consent Questionnaire Parts A and B (QuIC-A and QuIC-B). The experimental arm will involve the full length trial PIS, exposure to a two-page study aid and 10 online educational videos, followed by administration of the QuIC-A and QuIC-B. The primary endpoint will be the difference (using a one-sided two-sample t-test) in the QuIC-A score, which measures objective understanding, between the standard and experimental arm. Accrual target is at least 17 patients per arm to detect an 8 point difference (80% power, alpha 0.05).Ethics and disseminationEthics approval was granted by the National Health Service Health Research Authority on 15 June 2020-IRAS Project ID 277065, Protocol Number CCR5165, REC Reference 20/EE/0155. Results will be disseminated via publication in a relevant journal.Trial registration numberNCT04407676; Pre-results.
| S-EPMC8422487 | biostudies-literature
Project description:PurposeGeneral notification offers a possible alternative to written informed consent for pragmatic randomized controlled trials (pRCTs). It involves patients being informed through brochures, posters, and letters that research is being conducted simultaneously to providing clinical care and that patients will be enrolled in pRCTs without study-specific consent. A previous survey found that a substantial minority of respondents endorsed general notification. We aimed to know who is willing to enroll in this type of trials using general notification rather than written consent.MethodsThe previous study was a cross-sectional, probability-based survey, with a 2 × 2 factorial design. Two scenarios were assessed: two low-risk pRCTs in hypertension, one comparing two drugs with similar benefit/risk ratio and the other taking the same drug in the morning or at night. Each scenario had two routes: written consent vs verbal consent and written consent vs general notification. In this study, we were interested in the latter route in both scenarios. Respondents' preferences were measured based on their recommendation to the research ethics committee and the respondent's personal preference. We aimed to investigate the characteristics of those supporting general notification in either outcome or the variables explaining consistency and inconsistency between their personal preference and their recommendation. Based on the results of the original survey, we aimed to have at least 200 inconsistent respondents; to this end, the sample size was increased accordingly in a second wave of the survey.ResultsOne thousand six hundre and ten respondents were included; 1003 from the original survey and 607 new ones belonging to the second wave. Thirty-nine percent of respondents chose general notification as personal preference and/or recommendation. Respondents with lower education levels were more prone to accept general notification than those holding a university degree [OR (95% CI)], primary school [2.959 (2.069-4.232)], secondary school [2.899 (2.09-4.021)], or high school [1.620 (1.184-2.217)]. Also unemployed [1.372 (1.064-1.770)] and retired [1.445 (1.049-1.990)], but not students, showed preference for general notification in comparison with those employed. Individuals more than 24 years old and having received high school or university (or postgraduate) education were statistically significantly more consistent in their decisions.ConclusionsThirty-nine percent of respondents is open to not to be asked for their informed consent in low-risk pRCTs; of these, those being less educated and not having current job or being retired are significantly more open to general notification. The use of this alternative method to written consent for simultaneous conduct of pRCTs and care should be considered and educational programs settled up to, in the case of public acceptance, ensure its ethical appropriateness.
| S-EPMC5684310 | biostudies-literature
Project description:ImportancePotential research participants may assume that randomized trials comparing new interventions with older interventions always hypothesize greater efficacy for the new intervention, as in superiority trials. However, antibiotic trials frequently use "noninferiority" hypotheses allowing a degree of inferior efficacy deemed "clinically acceptable" compared with an older effective drug, in exchange for nonefficacy benefits (eg, decreased adverse effects). Considering these different benefit-harm trade-offs, proper informed consent necessitates supplying different information on the purposes of superiority and noninferiority trials.ObjectiveTo determine the degree to which the study purpose is explained to potential participants in randomized clinical trials of antibiotics and the degree to which study protocols justify their selection of noninferiority hypotheses and amount of "clinically acceptable" inferiority.Design and settingCross-sectional analysis of study protocols, statistical analysis plans (SAPs), and informed consent forms (ICFs) from clinical study reports submitted to the European Medicines Agency. The ICFs were read by both methodologists and patient investigators.Main outcomes and measuresProtocols and SAPs were used as the reference standard to determine prespecified primary hypothesis and record rationale for selection of noninferiority hypotheses and noninferiority margins. This information was cross-referenced against ICFs to determine whether ICFs explained the study purpose.ResultsWe obtained trial documents from 78 randomized trials with prespecified efficacy hypotheses (6 superiority, 72 noninferiority) for 17 antibiotics conducted between 1991 and 2011 that enrolled 39 407 patients. Fifty were included in the ICF analysis. All ICFs contained sections describing study purpose; however, none consistently conveyed study hypothesis to both methodologists and patient investigators. Methodologists found that 1 of 50 conveyed a study purpose. Patient investigators found that 11 of 50 conveyed a study purpose, 7 accurately and 4 inaccurately compared with the reference standard. Seventy-one of 72 noninferiority trial protocols or SAPs provided no rationale for selection of noninferiority hypothesis. None provided a clinical rationale for the chosen amount of decreased efficacy.Conclusions and relevancePatients were not accurately informed of study purpose, which raises questions regarding the ethics of informed consent in antibiotic trials. Noninferiority and superiority trials entail different benefit-harm trade-offs that must be conveyed for ethical informed consent.
| S-EPMC5710221 | biostudies-literature
Project description:Importance. Oncology trials often entail high-stakes interventions where potential for morbidity and fatal side effects, and for life-prolongation or cure, intensify bioethical issues surrounding informed consent. These challenges are compounded in multistage randomized trials, which are prevalent in oncology. Objective. We sought to elucidate the major barriers to informed consent in high-stakes oncology trials in general and the best consent practices for multistage randomized trials. Evidence Review. We queried PubMed for original studies published from January 1, 1990, to April 5, 2018, that focused on readability, quality, complexity or length of consent documents, motivation and sickness level of participants, or interventions and enhancements that influence informed consent for high-stakes oncologic interventions. Exclusion criteria included articles focused on populations outside industrialized countries, minors or other vulnerable populations, physician preferences, cancer screening and prevention, or recruitment strategies. Additional articles were identified through comprehensive bibliographic review. Findings. Twenty-seven articles were retained; 19 enrolled participants and 8 examined samples of consent documents. Methodologic quality was variable. This body of literature identified certain challenges that can be readily remedied. For example, the average length of the consent forms has increased 10-fold from 1987 to 2010, and patient understanding was shown to be inversely proportional to page count; shortening forms, or providing a concise summary as mandated by the revised Common Rule, might help. However, barriers to understanding that stem from deeply ingrained and flawed sociocultural perceptions of medical research seem more difficult to surmount. Although no studies specifically addressed problems posed by multiple sequential randomizations (such as change in risk-benefit ratio due to time-varying treatment responses or organ toxicities), the findings are likely applicable and especially relevant in that context. Concrete suggestions for improvement are proposed.
| S-EPMC6440043 | biostudies-literature
Project description:Informed consent discussions for elective abdominal aortic aneurysm (AAA) repair should reflect appropriate risks of the open or endovascular repair (EVAR), but few guidelines exist describing what surgeons should discuss. This study examines expert opinion regarding what constitutes informed consent.Design. We conducted an anonymous, web-based, national survey of vascular surgeons. Associations between surgeon characteristics and opinions regarding informed consent were measured using bivariate statistics; multivariable logistic regression was performed to estimate effects adjusted for covariates. Setting. Academic and private practice surgeons were surveyed. Subjects. United States members of the International Society for Vascular Surgery membership. Main Outcome Measure. Surgeons' self-reported opinions regarding the content of informed consent for AAA repair.A total of 199 surgeons completed the survey (response rate 51%). More than 90% of respondents reported that it was essential to discuss mortality risk for both procedures. However, only 60% and 30% of respondents reported that it was essential to discuss the risk of myocardial infarction and stroke, respectively. Opinions varied by procedure regarding the risks of impotence (32% vs 62%; EVAR vs open repair), reintervention (78% vs 17%), and rupture during long-term follow-up (57% vs 17%). Younger and private practice surgeons were more likely to discuss complications compared with older surgeons and those in academic practice. Surgeons who perform predominantly EVAR were more likely to quote higher mortality rates for open repair (odds ration [OR] = 3.1, 95% confidence interval [CI] = 1.4-6.4) and lower reintervention rates for EVAR (OR = 0.3, 95% CI = 0.1-0.7) compared with other surgeons.This is the first study of the practice of informed consent for AAA repair. The only risk that the vast majority of surgeons agreed should be included in informed consent for AAA repair was mortality. Significant variation exists regarding whether other complications should be discussed and what complication rates should be quoted. Surgeon characteristics may influence how risks are presented to patients. Further efforts are needed to develop guidelines to ensure consistent communication of appropriate risk during informed consent for AAA repair.
| S-EPMC2659171 | biostudies-literature
Project description:Objective:Methods to improve informed consent efficiency and effectiveness are needed for pragmatic clinical trials. We compared informed consent using a tablet computer to a paper approach to assess comprehension and satisfaction of patients and clinic staff for a future osteoporosis clinical trial. Methods:Nine community-based practices identified and recruited patients to compare the informed consent processes (tablet vs. paper) in a mock osteoporosis clinical trial. The tablet informed consent included an animation summarizing the trial, complete informed consent document, and questions to assess and reinforce comprehension of the study. Participants were women age ?55 years with ?1 year of alendronate use. We surveyed participants to assess comprehension and satisfaction and office staff for satisfaction and perceived time demands. Results:The nine practices enrolled 33 participants. There was not a significant difference in comprehension between the tablet vs. paper informed consent [mean (SD) tablet: 12.2 (1.0) vs. paper: 11.4 (1.7)]. Office staff preferred the tablet to the paper informed consent for identifying potential study participants (two-sided t-test p = 0.02) despite an increased perceived time spent to complete the tablet process [tablet: 28.3 min (SD 16.3) vs. paper: 19.0 min (SD 6.9); p = 0.08]. Conclusions:Although, there were no significant differences in participant satisfaction and comprehension with the tablet informed consent compared to a paper informed consent, patients and office staff trended towards greater satisfaction with the tablet informed consent. Larger studies are needed to further evaluate the utility of electronic informed consent in pragmatic clinical trials.
| S-EPMC5935867 | biostudies-literature
Project description:ImportancePragmatic clinical trials that seek informed consent after randomization (ie, postrandomization consent) are increasingly used, but debate on ethics persists because control arm patients are not specifically informed about the trials and randomization occurs before consent for the trials. The public's attitude toward postrandomization consent trials is unknown, but the way the trials are described could bias people's views.ObjectivesTo assess the attitudes of the US general public toward postrandomization informed consent for pragmatic trials and to measure potential framing and other factors associated with those attitudes.Design, setting, and participantsAn online, 2 × 2 experimental survey (fielded between February 23 and April 3, 2018) portraying 4 scenarios of postrandomization informed consent (with prior broad consent for medical record use) was conducted. These scenarios included traditional randomized clinical trial language framing vs alternative framing in a high-stakes trial (ie, survival in leukemia) or low-stakes trial (ie, blood glucose level in diabetes). A total of 3793 individuals invited to participate were part of an existing panel representative of the US general public (GfK KnowledgePanel).Main outcomes and measuresThe proportion of participants who would recommend that an ethics review board approve a postrandomization consent pragmatic trial.ResultsA total of 2042 of 3739 invitees (54.6%) responded; after exclusion of 38 incomplete surveys, 2004 participants were included in the analysis. Of these, 997 (49.8%) were women, 1440 (71.9%) were white non-Hispanic, 199 (9.9%) were black non-Hispanic, and 233 (11.6%) were Hispanic. Mean (SD) age was 47.5 (17.4) years. Across scenarios, weighted data showed that 75.4% of the participants would recommend approval of the postrandomization consent pragmatic trial, 20.4% would probably not recommend approval, and 4.2% would definitely not recommend approval. Approval was not sensitive to framing language (traditional vs new framing in high-stakes scenario, 74.3% vs 76.8%, P = .40; in low-stakes scenario, 77.7% vs 72.9%, P = .10) or to the stakes (low vs high stakes in traditional framing, 77.7% vs 74.3%, P = .25; in new framing, 72.9% vs 76.8%, P = .18). Better understanding of the postrandomization consent design was associated with higher rate of approval (78.1% vs 65.0%, P = .002 for high-stakes scenario; 77.2% vs 64.9%, P = .004 for low-stakes scenario), especially among those with less education. However, opinions about personal involvement in the control arm were more cautious (range depending on scenario, 45.6%-59.7%) and sensitive to stakes but not to framing.Conclusions and relevanceThe public's generally high rate of approval of the ethics of postrandomization informed consent for pragmatic trial designs does not appear to be affected by whether postrandomization consent design is framed using traditional randomized clinical trial terminology, regardless of the stakes of the trial. Promoting better understanding of the design may increase its acceptance by the public.
| S-EPMC6324565 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:No standard approach to obtaining informed consent for stroke thrombolysis with tPA (tissue-type plasminogen activator) currently exists. We aimed to assess current nationwide practice patterns of obtaining informed consent for tPA. METHODS:An online survey was developed and distributed by e-mail to clinicians involved in acute stroke care. Multivariable logistic regression analyses were performed to determine independent factors contributing to always obtaining informed consent for tPA. RESULTS:Among 268 respondents, 36.7% reported always obtaining informed consent and 51.8% reported the informed consent process caused treatment delays. Being an emergency medicine physician (odds ratio, 5.8; 95% confidence interval, 2.9-11.5) and practicing at a nonacademic medical center (odds ratio, 2.1; 95% confidence interval, 1.0-4.3) were independently associated with always requiring informed consent. The most commonly cited cause of delay was waiting for a patient's family to reach consensus about treatment. CONCLUSIONS:Most clinicians always or often require informed consent for stroke thrombolysis. Future research should focus on standardizing content and delivery of tPA information to reduce delays.
| S-EPMC5829003 | biostudies-literature