Participants' informed consent in adaptive, platform drug trials in hospitalized COVID-19 patients: Not all approaches are ethically acceptable.
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ABSTRACT:
SUBMITTER: Dal-Re R
PROVIDER: S-EPMC9236980 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe information provided to participants of adaptive platform trials assessing therapies for COVID-19 inpatients is unknown. We aim to evaluate it by reviewing participant information sheets/informed consent forms (PIS/ICFs).MethodsWe searched the Cochrane COVID-19 Study Register and ClinicalTrials.gov (28 March 2022) to identify non-industry-sponsored adaptive platform phase 2+ trials with publicly available protocols and PIS/ICFs, selecting versions closest to the initial one. We assessed the elements of information included in the Good Clinical Practice guidelines and the Declaration of Helsinki as present, absent, or deficient (incompletely described).ResultsWe included PIS/ICFs of 11 trials (ACCORD-2, ACTIV-1IM, Bari-SolidAct, CATALYST, Discovery, HEAL-COVID, ITAC, RECOVERY, REMAP-COVID, Solidarity and TACTIC-R), which were 4-32 pages long (median (md) = 11). Between two and 11 (md = 6) of the 25 different elements of information assessed were omitted or deficiently described in the PIS/ICFs of the 11 trials. Information about providing trial results, investigators' conflicts of interest, post-study provisions, payment to and anticipated expenses for participants, number of participants, and on whether participants will receive new information that could impact their decision on staying in the trial, were omitted or deficiently described in at least five PIS/ICFs.ConclusionsInvestigators failed to include a few important elements of information in the trial's PIS/ICF deemed relevant by international standards. In protocols of future trials, investigators should explain why elements of information specified in the Good Clinical Practice guidelines and/or by the Declaration of Helsinki were omitted from the PIS/ICFs.
| S-EPMC10173897 | biostudies-literature
Project description:Cognitive impairment is a characteristic of schizophrenia. This impairment may affect the retention of information required for ongoing knowledgeable participation in clinical trials. This study monitored retention of study-related knowledge-including assessment of therapeutic misconception-in people with stable, DSM-IV schizophrenia during participation in placebo-controlled clinical trials of adjunctive agents. Stability was defined as being on an antipsychotic with no change in medication or dose over the previous 4 weeks.This longitudinal study assessed retention of clinical trial-related consent information. Individuals enrolling in 1 of 8 clinical trials were approached for participation. Participants came from research clinics and community mental health centers. At baseline, clinical trial consent forms were reviewed and study knowledge assessed. Participants were randomized to follow-up assessments at weeks 1, 4, and 8; weeks 4 and 8; or at week 8 only. Clinical trial consent forms were not rereviewed at any follow-up visit.Fifty-nine participants were enrolled; analysis included 52 participants with at least 1 follow-up visit. Study knowledge did not decrease meaningfully in any group. Therapeutic misconception was not observed in participants during the study. The group assessed most frequently demonstrated significant improvement over baseline (t44 = 3.43, P = .001). Retention of study knowledge was not related to symptoms but had a weak correlation with cognitive capacity (R = 0.28, P = .07). Performance did not differ between participants from research clinics and those from community mental health centers.Clinically stable people with schizophrenia enrolling in a placebo-controlled adjunctive medication study, once determined to have capacity to consent to a clinical trial, retained appropriate study knowledge for at least 8 weeks. In the absence of a specific reason to suspect a loss of decisional capacity, there appears to be no need to routinely reevaluate participants during this type of clinical trial.
| S-EPMC4482016 | biostudies-literature
Project description:BackgroundAlthough phase I clinical trials are the gateway to progress in cancer therapies, this setting poses ethical challenges to ensure that patients provide consent free from misunderstandings of therapeutic intent or unrealistic expectations of benefit. The design of phase I oncology trials has evolved rapidly over time and today includes more targeted agents and combinations of experimental drugs with standard drugs, which may further complicate how patients understand phase I research participation.MethodsWe conducted semistructured interviews regarding motivations, decision making, and understanding of trial purpose nested within a phase I clinical trial of a novel PI3kinase inhibitor combined with a standard oral chemotherapy in 18 participants.ResultsFewer than half of patients correctly identified the safety and dosing objectives. The inclusion of a targeted agent was attractive to participants and was perceived as an indicator of less toxic or more efficacious therapy, with less appreciation for added risks. The significance of a cellular drug target, without a known predictive biomarker of response, was unclear to patients. The inclusion of a standard drug in the regimen attracted patients with more treatment options than traditional first-in-human participants. Patients frequently expressed a realistic understanding of prognosis and uncertainty of benefit, but simultaneous hopes for extraordinary outcomes.ConclusionNovel phase I oncology trial designs may attract patients with less constrained treatment options, but the inclusion of targeted drugs and combinations including standard chemotherapies is likely to complicate understanding of safety and dosing objectives and likelihood of personal benefit for purposes of informed consent.
| S-EPMC5640413 | biostudies-literature
Project description:BackgroundThe Final Rule regulations were developed to allow exception from informed consent (EFIC) to enable clinical trial research in emergency settings where major barriers exist for informed consent. There is little known evidence of the effect of the Final Rule in minority enrollment in clinical trials, particularly in traumatic brain injury (TBI) trials. A clinical trial funded by the National Institute of Neurological Disorders and Stroke was conducted to study the effects of erythropoietin on cerebral vascular dysfunction and anemia in subjects with TBI. There were periods of time when EFIC was and was not available for enrollment into the study.PurposeTo explore the effect of EFIC availability on TBI trial enrollment of minority versus non-minority subjects.MethodsMinority status of screened (n = 289) and enrolled (n = 191) TBI subjects was determined for this study. We tested for the presence of a minority and EFIC availability interaction in a multiple logistic regression model after controlling for EFIC and minority group main effects and other covariates.ResultsAn interaction between the availability of EFIC minority and non-minority enrollment was not detected (odds ratio = 1.22; 95% confidence interval (CI) = 0.29-5.16).LimitationsOur study was conducted at a single site, and the CI for the EFIC and minority interaction term was wide. Therefore, a small interaction effect cannot be ruled out.ConclusionEFIC increased the odds of being enrolled regardless of minority status.
| S-EPMC3974159 | biostudies-literature
Project description: Not available
| S-EPMC4117650 | biostudies-literature
Project description:BackgroundFormal checks of participant understanding are now widely recommended to improve informed consent processes. However, the views of the participants these assessments are designed to protect are rarely considered. In this paper the findings of a qualitative study aimed at documenting community reactions to a semi-structured questionnaire ('quiz') are reported. The quiz was administered to 189 mothers after consenting for their children to participate in a malaria vaccine trial on the Kenyan Coast.MethodsOnce the malaria vaccine trial was underway, focus group discussions were held with some of these mothers (nine groups; 103 mothers), and with community-based field staff attached to the malaria vaccine trial (two groups of five workers). Individual interviews with other trial staff were also held.ResultsThe quiz prompted community members to voice concerns about blood sampling and vaccine side-effects, thereby encouraging additional discussions and interactions between the research team and potential study participants. However, it also caused significant upset and concern. Some of the quiz questions, or the way in which they were asked, appeared to fuel misconceptions and fears, with potentially negative consequences for both the study and community members.ConclusionFormal approaches to checking study understanding should be employed with sensitivity and caution. They are influenced by and impact upon complex social relationships between and among researchers and community members. Adequate consideration of these contexts in assessments of understanding, and in responding to the issues raised, requires strong social science capacity.
| S-EPMC2204020 | biostudies-literature
Project description:BACKGROUND:Significant debate surrounds the issue of whether written consent is necessary for pragmatic randomized, controlled trials (RCTs) with low risk. OBJECTIVE:To assess the U.S. public's views on alternatives to written consent for low-risk pragmatic RCTs. DESIGN:National experimental survey (2 × 2 factorial design) examining support for written consent versus general notification or verbal consent in 2 research scenarios. SETTING:Web-based survey conducted in December 2014. PARTICIPANTS:2130 U.S. adults sampled from a nationally representative, probability-based online panel (response rate, 64.0%). MEASUREMENTS:Respondent's recommendation to an ethics review board and personal preference as a potential participant on how to obtain consent or notification in the 2 research scenarios. RESULTS:Most respondents in each of the 4 groups (range, 60.3% to 71.5%) recommended written informed consent, and personal preferences were generally in accord with that advice. Most (78.9%) believed that the pragmatic RCTs did not pose additional risks, but 62.5% of these respondents would still recommend written consent. In contrast, a substantial minority in all groups (28.5% to 39.7%) recommended the alternative option (general notification or verbal consent) over written consent. LIMITATION:Framing effects could have affected respondents' attitudes, and nonrespondents may have differed in levels of trust toward research or health care institutions. CONCLUSION:Most of the public favored written informed consent over the most widely advocated alternatives for low-risk pragmatic RCTs; however, a substantial minority favored general notification or verbal consent. PRIMARY FUNDING SOURCE:Time-sharing Experiments for the Social Sciences and Intramural Research Program of the National Institutes of Health Clinical Center.
| S-EPMC5573142 | biostudies-literature
Project description:BackgroundThe 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.MethodsThis 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.ResultsOverall, 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.ConclusionsAs 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-literature
Project description:In a cluster randomised trial (CRT), intact groups-such as communities, clinics or schools-are randomised to the study intervention or control conditions. The issue of informed consent in CRTs has been particularly challenging for researchers and research ethics committees. Some argue that cluster randomisation is a reason not to seek informed consent from research participants. In fact, systematic reviews have found that, relative to individually randomised trials, CRTs are associated with an increased likelihood of inadequate reporting of consent procedures and inappropriate use of waivers of consent. The objective of this paper is to clarify this confusion by providing a practical and useful framework to guide researchers and research ethics committees through consent issues in CRTs. In CRTs, it is the unit of intervention-not the unit of randomisation-that drives informed consent issues. We explicate a three-step framework for thinking through informed consent in CRTs: (1) identify research participants, (2) identify the study element(s) to which research participants are exposed, and (3) determine if a waiver of consent is appropriate for each study element. We then apply our framework to examples of CRTs of cluster-level, professional-level and individual-level interventions, and provide key lessons on informed consent for each type of CRT.
| S-EPMC8477335 | 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