Dataset Information

Rates of and Factors Associated With Patient Withdrawal of Consent in Cancer Clinical Trials.

ABSTRACT:

Importance

Patient withdrawal of consent from a cancer clinical trial is defined as a patient's volitional cessation of participation in all matters related to a trial. It can undermine the trial's purpose, make the original sample size and power calculations irrelevant, introduce bias between trial arms, and prolong the time to trial completion.

Objective

To report rates of and baseline factors associated with withdrawal of consent among patients in cancer clinical trials.

Design, setting, and participants

This multisite observational cohort study was conducted through the Alliance for Clinical Trials in Oncology. Patient withdrawal was defined as a patient's voluntary termination of consent to participate anytime during trial conduct. Baseline patient- and trial-based factors were investigated for their associations with patient withdrawal within the first 2 years using logistic regression models. All patients who participated in cancer therapeutic clinical trials conducted within the Alliance for Clinical Trials in Oncology from 2013 through 2019 were included. The data lock date was January 23, 2022.

Main outcomes and measures

The percentage of patients who withdrew consent in 2 years and factors associated with withdrawal of consent.

Results

A total of 11 993 patients (median age, 62 years; 67% female) from 58 trials were included. Within 2 years, 1060 patients (9%) withdrew from their respective trials. Two-year rates of withdrawal were 5.7%, 7.6%, 8.5%, 7.8%, 8.4%, 9.5%, and 9.8% for each of the respective years from 2013 through 2019. In multivariable analyses, Hispanic ethnicity (odds ratio [OR], 1.67; 95% CI, 1.30-2.15; P < .001), randomized design with placebo (OR, 1.64; 95% CI, 1.38-1.94; P < .001), and patient age 75 years and older (OR, 1.39; 95% CI, 1.12-1.72; P = .003) were associated with higher likelihood of withdrawal by 2 years. Use of radiation was associated with patient retention (OR, 0.68; 95% CI, 0.54-0.86; P = .001).

Conclusions and relevance

In this cohort study, rates of withdrawal of consent were less than 10% and appeared consistent over time. Factors that are associated with withdrawal of consent should be considered when designing trials and should be further studied to learn how they can be favorably modified.

SUBMITTER: Hillman SL

PROVIDER: S-EPMC10288373 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rates of and Factors Associated With Patient Withdrawal of Consent in Cancer Clinical Trials.

Hillman Shauna L SL Jatoi Aminah A Strand Carrie A CA Perlmutter Jane J George Suzanne S Mandrekar Sumithra J SJ

JAMA oncology 20230801 8

<h4>Importance</h4>Patient withdrawal of consent from a cancer clinical trial is defined as a patient's volitional cessation of participation in all matters related to a trial. It can undermine the trial's purpose, make the original sample size and power calculations irrelevant, introduce bias between trial arms, and prolong the time to trial completion.<h4>Objective</h4>To report rates of and baseline factors associated with withdrawal of consent among patients in cancer clinical trials.<h4>Des ...[more]

PMID: 37347469

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Project description:BackgroundOur purpose was to identify physicians' individual characteristics, attitudes, and organizational contextual factors associated with higher enrollment of patients in cancer clinical trials among physician participants in the National Cancer Institute's Community Clinical Oncology Program (CCOP). We hypothesized that physicians' individual characteristics, such as age, medical specialty, tenure, CCOP organizational factors (i.e. policies and procedures to encourage enrollment), and attitudes toward participating in CCOP would directly determine enrollment. We also hypothesized that physicians' characteristics and CCOP organizational factors would influence physicians' attitudes toward participating in CCOP, which in turn would predict enrollment.MethodsWe evaluated enrollment in National Cancer Institute-sponsored cancer clinical trials in 2011 among 481 physician participants using Structural Equation Modeling. The data sources include CCOP Annual Progress Reports, two surveys of CCOP administrators and physician participants, and the American Medical Association Masterfile.ResultsPhysicians with more positive attitudes toward participating in CCOP enrolled more patients than physicians with less positive attitudes. In addition, physicians who practiced in CCOPs that had more supportive policies and practices in place to encourage enrollment (i.e. offered trainings, provided support to screen and enroll patients, gave incentives to enroll patients, instituted minimum accrual expectations) also significantly enrolled more patients. Physician status as CCOP Principal Investigator had a positive direct effect on enrollment, while physician age and non-oncology medical specialty had negative direct effects on enrollment. Neither physicians' characteristics nor CCOP organizational factors indirectly influenced enrollment through an effect on physician attitudes.ConclusionWe examined whether individual physicians' characteristics and attitudes, as well as CCOP organizational factors, influenced patient enrollment in cancer clinical trials among CCOP physicians. Physician attitudes and CCOP organizational factors had positive direct effects, but not indirect effects, on physician enrollment of patients. Our results could be used to develop physician-directed strategies aimed at increasing involvement in clinical research. For example, administrators may want to ensure physicians have access to support staff to help screen and enroll patients or institute minimum accrual expectations. Our results also highlight the importance of recruiting physicians for volunteer clinical research programs whose attitudes and values align with programmatic goals. Given that physician involvement is a key determinant of patient enrollment in clinical trials, these interventions could expand the overall number of patients involved in cancer research. These strategies will be increasingly important as the CCOP network continues to evolve.

Project description:IntroductionThe subjective assessment of the adequacy of informed consent for clinical trials, and the potential difficulties associated with it, has led several studies to develop objective measures of informed consent for clinical trials. These objective measures of informed consent are often specific to a particular population or clinical condition and largely focus on understanding of (some or all of) the key elements of informed consent. Many of the developed tools are study-specific, but some validated measures exist. Of these validated measures, those which are reported by participants are of particular interest. Whether these objective tools conceptualize and measure informed consent in the same way is not known. As such, it is not clear whether meta-analyzing data from studies reporting different tools is worthwhile. The aim of this systematic review was to critically appraise the evidence on the overall conceptualisation and item content of validated patient reported measures of informed consent for clinical trials, and to identify core domains of potential importance for informed consent.MethodsA systematic search of the literature was conducted to identify relevant articles that described the development, and/or validation, of patient-reported measures of adequacy of informed consent for randomised controlled trials. Data was synthesised by classifying the items identified into domains and sub-domains which were determined by the nomenclature reported in included studies. Both for descriptions of included studies and of the instruments reported in those studies, descriptive statistics were used to describe general information and instrument detail. A narrative synthesis of the instruments and their inter-related domains and subdomains was conducted to identify areas of both convergence and divergence.ResultsThe search identified 8193 citations. After screening titles and abstracts, 29 full text articles were retrieved for further assessment. Of these 29, 14 complied with our pre-specified inclusion criteria with 15 not being eligible. Of the 14 instruments, three explicitly reported a theoretical or conceptual framework underpinning their development, a further three implicitly referred to the 'conceptual dimensions of informed consent' or 'principles of research ethics' as informing their development and eight reported no guiding theoretical framework. Only three of the 14 studies reported patient or public involvement in the development of the tool. One hundred and seventy nine items were included across the 14 instruments. The primary focus of the instruments was on understanding. Five core domains were identified which included: Autonomy; Consequences; Expectations; Purpose; and Individualisation. There was substantial variability in the coverage of different domains across measures.ConclusionsThis study demonstrated the variability in the theoretical underpinning, development and domain coverage of existing patient-reported measures of informed consent for clinical trials. The conceptualisation of informed consent could benefit from being extended from a narrow focus on understanding to include broader considerations of decision-making. Meaningful involvement of potential trial participants during development of measures critical for tool relevance is also lacking. The identification of the key domains relevant to all stakeholders which could be measured to assess the informed consent process for clinical trials is needed.

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.

Project description:ImportanceEnsuring valid informed consent (IC) prior to enrollment in clinical trials is a fundamental ethical right.ObjectiveTo assess whether social determinants of health (SDOH) and related sociocontextual factors are associated with parental IC comprehension in therapeutic childhood cancer clinical trials.Design, setting, and participantsThis cross-sectional study prospectively enrolled 223 parents of children with newly diagnosed cancer at Rady Children's Hospital San Diego, a large quaternary academic center in California, from October 1, 2014, to March 31, 2021. Linear mixed effects models were used to assess whether IC comprehension overall and by domain (purpose, procedures, and randomization; risks and benefits; alternatives; and voluntariness) were associated with SDOH and sociocontextual factors. Data were analyzed from January 1, 2022, to July 31, 2023.ExposuresInformed consent for a therapeutic childhood cancer clinical trial.Main outcomes and measuresThe primary outcome of interest was IC comprehension and its associations with SDOH (marital status, language, educational attainment, employment, insurance type, socioeconomic status, and health literacy) and sociocontextual factors (ethnicity, satisfaction with informed consent, and cancer type).ResultsOf 223 parents, 172 (77.1%) were aged 18 to 44 years, 111 (49.8%) were Hispanic, 152 (68.2%) were women, and 163 (73.1%) were married. In terms of race, 2 (0.9%) were American Indian or Alaska Native, 22 (9.9%) were Asian or Pacific Islander, 8 (3.6%) were Black, 149 (66.8%) were White, and 42 (18.8%) were more than 1 race. In multivariable linear mixed-effects analyses, limited vs adequate health literacy was associated with lower comprehension of informed consent overall (mean [SD], 68.28 [11.81] vs 79.24 [11.77]; β estimate, -9.02 [95% CI, -12.0 to -6.07]; P < .001) and with lower comprehension of the purpose, procedures, and randomization (mean [SD], 65.00 [12.64] vs 76.14 [11.53]; β estimate, -7.87 [95% CI, -10.9 to -4.85]; P < .001); risks and benefits (mean [SD], 62.84 [20.24] vs 73.14 [20.86]; β estimate, -10.1 [95% CI, -15.6 to -4.59]; P < .001); alternatives (mean [SD], 54.27 [43.18] vs 82.98 [34.24]; β estimate, -14.3 [95% CI, -26.1 to -2.62]; P .02); and voluntariness (mean [SD], 76.52 [24.33] vs 95.39 [13.89]; β estimate, -9.14 [95% CI, -14.9 to -3.44]; P = .002) domains. Use of Spanish vs English language for medical communication was associated with lower comprehension overall (mean [SD], 66.45 [12.32] vs 77.25 [12.18]; β estimate, -5.30 [95% CI, -9.27 to -1.34]; P = .01) and with lower comprehension of the purpose, procedures, and randomization (mean [SD], 63.33 [11.98] vs 74.07 [12.52]; β estimate, -4.33 [95% CI, -8.43 to -0.23]; P = .04) and voluntariness (mean [SD], 70.83 [24.02] vs 92.54 [17.27]; β estimate, -9.69 [95% CI, -16.8 to -2.56]; P = .009) domains.Conclusions and relevanceIn this cross-sectional study including parents of children with newly diagnosed cancer who provided IC for their child's participation in a therapeutic clinical trial, limited health literacy and use of Spanish language for medical communication were associated with lower comprehension of IC. These findings suggest that, in this setting, parents with limited health literacy or those who use Spanish language for medical communication may not fully comprehend IC and therefore may not make truly informed decisions. These findings support the investigation of interventions, across pediatric disciplines, tailored to the participant's language and health literacy level to improve IC comprehension, particularly in racial and ethnic minority populations.

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.

Dataset Information

Rates of and Factors Associated With Patient Withdrawal of Consent in Cancer Clinical Trials.

Importance

Objective

Design, setting, and participants

Main outcomes and measures

Results

Conclusions and relevance

Publications

Rates of and Factors Associated With Patient Withdrawal of Consent in Cancer Clinical Trials.

Similar Datasets

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