Consent Process For Clinical Trials Research Articles

Informed consent process in clinical trials: development of a patient-reported questionnaire

ObjectiveTo develop a Spanish-language questionnaire aimed at evaluating patients’ perception of the way they are briefed and their consent is obtained prior to participating in clinical trials. The tool was conceived to evaluate the following aspects: patients’ personal experience, the way the informed consent process was implemented in practice, patients’ level of satisfaction with the process, and their level of understanding of the study itself. MethodThis study looked into the development, adaptation and validation of a self-administered questionnaire intended to evaluate the informed consent process on the basis of information provided by respondents. The steps followed included: literature review, generation of an items pool, drawing up of the questionnaire, expert review, piloting, and reading ease optimization and analysis. A commonly-used English-language questionnaire was evaluated, translated into Spanish and adapted so as to determine the extent to which subjects understood the information conveyed to them. ResultsIn its final version, the questionnaire came to comprise four sections intended to evaluate: 1) socio-demographic data; 2) practical aspects related with the development of the informed consent process; 3) patients’ perception of the process (satisfaction, expectations and motivations); and 4) their level of understanding. Understanding was gaged using the QuIC questionnaire, translated by three bilingual translators. Additional questions were included to evaluate the understanding of concepts related with blinding and therapeutic misconception. The validity of the contents was evaluated by consulting with an expert panel. The reading ease analysis yielded an IFSZ score of 64.34, equivalent to an “average difficulty’ grade on the Inflesz scale. In the pilot study, interviews were held with 32 patients, who did not appear to have any difficulties in understanding the questions asked of them or in using Likert-type scales to respond. Mean completion time was 16.6 minutes. ConclusionsThe tool developed as part of this study has shown itself capable of providing an understanding and an assessment of the informed consent process from the perspective of a patient who is invited to participate in a clinical trial. Implementation of the questionnaire could help investigators ascertain that the process has been correctly executed and identify specific aspects that may require to be changed or optimized.

Fragmented understanding: exploring the practice and meaning of informed consent in clinical trials in Ho Chi Minh City, Vietnam

BackgroundThe informed consent process in clinical trials has been extensively studied to inform the development processes which protect research participants and encourage their autonomy. However, ensuring a meaningful informed consent process is still of great concern in many research settings due to its complexity in practice and interwined socio-cultural factors.ObjectivesThis study explored the practices and meaning of the informed consent process in two clinial trials conducted by Oxford University Clinical Research Unit in collaboration with the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.MethodsWe used multiple data collection methods including direct observervations, in-depth interviews with study physicians and trial participants, review of informed consent documents from 2009 to 2018, and participant observation with patients’ family members. We recruited seven physicians and twenty-five trial participants into the study, of whom five physicians and thirteen trial participants completed in-depth interviews, and we held twenty-two direct observation sessions.ResultsWe use the concept “fragmented understanding” to describe the nuances of understanding about the consent process and unpack underlying reasons for differing understandings.ConclusionsOur findings show how practices of informed consent and different understanding of the trial information are shaped by trial participants’ characteristics and the socio-cultural context in which the trials take place.

Co-creation of information materials within the assent process: From theory to practice.

The informed consent process is key to safeguarding the autonomy of the participant in medical research. For this process to be valid, the information presented to the potential participant should meet their needs and be understood by them. The i-CONSENTproject has developed 'Guidelines for adapting the informed consent process in clinical trials' which aim to improve informed consent so that they are easier to understand and better adapted to the needs and preferences of the target population. The best way to tailor information to the characteristics and preferences of the target population is to involve the community itself. Following guidelines developed by i-CONSENT, assent materials were co-created for a mock clinical trial of the human papillomavirusvaccine in adolescents. During the process, two design thinking sessions were conducted involving a total of 10 children and 5 parents. The objectives of the sessions were to find out the children's opinion of the informed consent (assent in their case) process in clinical trials, identify the parts that were most difficult to understand and alternatives for their presentation and wording, identify the preferred formats for receiving the information and the main characteristics of these formats, design a video explaining the clinical trial and evaluate a tool for assessing comprehension. Assent materials were co-created in three formats: a web-based material following a layered approach; a video in story format; a pdf document with an innovative way of presenting information compared to traditional assent documents. In addition, the Comprehension of Assent Questionnairewas co-designed, based on the Quality of Informed Consentquestionnaire. The design thinking methodology has proven to be an easy and useful tool for involving children in designing information tailored to their needs and preferences. A sample of the target population participated in the design and piloting of the materials created using design thinking methodology. In addition, patient representatives participated in the design and evaluation of the guidelines developed by the i-CONSENT project that were followed for the development of the materials in this study.

Expectations, experiences and preferences of patients and physicians in the informed consent process for clinical trials in oncology.

The aim of the present study was to explore (1) informed consent (IC)representations, level of understanding, needs, and factors that influence the willingness of cancer patients to participate in randomized controlled trials (RCTs) (phase I) and (2) representations, experiences, and critical issues of physicians involved in the same process (phase II). Semi-structured interviews were conducted with 20 cancer patients who had been asked to enroll in a phase II/III RCT (phase I). Two focus groups were conducted with 13 physicians enrolled in the same process (phase II). The content produced was analyzed through a thematic analysis. The themes that emerged in the first phase I were grouped into six categories: IC representation, randomization, experimentation, meeting with the physician, factors that influence the willingness to participate, and trial participants' needs. The themes emerged in the phase II were grouped into four: IC representation, critical issues of the IC, relationship, and recruitment of trial participants. Each theme is articulated into sub-themes and deeply discussed. This study highlights (1) the gap between what is ethically demanded in a RCT consultation and the reality of the situation and (2) the difference in perceptions between patients and physicians with reference to the meaning, objectives, and level of understanding of IC.

Role of Health Literacy, Acculturation, and Socio-Demographics on Perception of Voluntariness during Informed Consent for Pediatric Leukemia Clinical Trials

Introduction :Valid consent for research requires that the decision be both informed and voluntary. For parents and legal guardians, it is essential that they fully understand their role when giving consent to participation of their child in research. Previous studies on parental informed consent in pediatric settings have focused largely on disclosure and understanding (Kodish, JAMA, 2004; Chappuy, Arch Dis Child, 2010) and motivations for agreeing to or declining research participation (Petersen, Pediatr Blood Cancer, 2013). When presented with a cancer clinical trial for their child, parents often do not understand the many components of informed consent, including voluntariness of participation (De Vries, BMC Med Ethics, 2011). In addition, individuals with limited English proficiency have reported lower understanding and satisfaction during informed consent (Breese, J Empir Res Hum Res Ethics, 2007). There is limited research on perception of voluntariness of participation in pediatric leukemia clinical trials. The aim of this study was to examine socio-demographic and contextual correlates of perception of voluntariness, decisional regret, and satisfaction in parents who had consented to participation of their child in a clinical trial for leukemia treatment. We focused on characterizing differences between non-Hispanics and Hispanics, as the latter is the fastest growing ethnic group in the U.S.Methods :Parents/guardians (n=97) of children aged 0-17 years with newly diagnosed leukemia, who had consented to participation of their child in a clinical trial for leukemia treatment at Rady Children's Hospital San Diego were prospectively recruited. Of the 135 parents approached to participate in our study, 26 (19.3%) declined and 12 (11.0%) withdrew after enrollment. Reasons for declining or withdrawing included feeling overwhelmed, having no time, or having no interest in the study. Participants completed questionnaires assessing perception of voluntariness, decisional regret, satisfaction, health literacy, socio-demographics, and acculturation level, if Hispanic (Table 1). Perception of voluntariness, decisional regret, and satisfaction outcomes were analyzed by socio-demographics, health literacy, and acculturation levels using logistic regression.Results :Ninety-seven participants were surveyed, including 50 (51.5%) Hispanic and 47 (48.5%) non-Hispanic. Demographic characteristics of the participants are shown in Table 2. We found that higher health literacy was associated with higher perception of voluntariness (p<0.001), socioeconomic status (SES) (p<0.001), and acculturation (p<0.001). Hispanic participants reported lower health literacy (p<0.001) compared to non-Hispanic participants. Spanish-speaking participants reported lower health literacy (p<0.001), lower perception of voluntariness (p=0.048), and lower acculturation (p<0.001) compared to English-speaking participants. In addition, participants with Medicaid reported lower health literacy (p<0.001) and lower SES (p<0.001) compared to participants with private insurance. Finally, participants with lower education levels reported lower health literacy (p<0.001). Decisional regret was overall low and satisfaction was overall moderately high across all subgroups and neither was significantly impacted by socio-demographics, health literacy, or acculturation.Conclusions :In this study, with equivalent numbers of Hispanic and Non-Hispanic participants, we found that Hispanic parents of children with newly diagnosed leukemia, and particularly Spanish-speakers, had inadequate health literacy and perception of voluntariness, despite overall high rates of satisfaction with the informed consent process for clinical trials. To our knowledge, this is the first study to associate lower health literacy with lower perception of voluntariness in parents of children with newly diagnosed leukemia. True voluntariness in participation is essential to the ethical practice of informed consent, and our study suggests that many Hispanics parents and those with limited English proficiency are not making truly informed decisions for their child with cancer. It is imperative to improve the informed consent process and facilitate informed decision making with culturally and linguistically appropriate interventions tailored to this vulnerable population. [Display omitted] DisclosuresAristizabal:American Society of Hematology Scholar Award: Other: ASH Scholar Award for the submitted abstract, Research Funding; American Society of Pediatric Hematology/Oncology Clinician-Educator Award: Research Funding; Alex Lemonade Stand Foundation Psychosocial Grant: Research Funding; NIH/CTSA: Other: Pilot Grant, Research Funding. M:University of California San Diego School of Medicine Research Fellowship: Research Funding.

Digital solutions to improve the informed consent process for clinical trials

• Informed consent (IC) is the corner stone to protecting participants in human subject's research. • The current consent process doesn't ensure that potential participants have sufficient comprehension of the information given during the IC process. • This lack of comprehension has a negative effect on the process of clinical research as it may lengthen recruitment time or increase the rate of dropouts later. • Digital consent is a recent innovation aiming to improve understanding by presenting the consent in an interactive technology-based patient-engagement manner. • Digital consent is predicted to improve comprehension among potential research participants which will improve the overall quality of human subject research.

Awareness and Collaboration Across Stakeholder Groups Important for eConsent Achieving Value-Driven Adoption

BackgroundWhile the shift to digital technologies is pervasive across multiple industries, the informed consent process for clinical trials remains largely paper-based. Given the inefficiencies in the traditional process and the increasing complexity of clinical studies, the current approach at times may raise challenges with respect to quality, compliance, participant understanding, and trial retention. Electronic informed consent (eConsent) is an enabling clinical technology to potentially address these issues by using multimedia components to create an interactive participant experience and improve data quality.MethodsThe TransCelerate eConsent Initiative conducted a multifaceted engagement approach to better understand the perceptions, experiences, and concerns of impacted stakeholders, including participants, sites, ethics committees, and health authorities.ResultsWhile all stakeholders were supportive of the use of multimedia components to deliver study information, several stakeholder-specific concerns were noted. Participant feedback, as collected through surveys (n = 3045) and an advisory board (n = 10), suggests that some participants may have data privacy concerns and a diversity of preferences for multimedia presentation. Site interviews (n = 9) suggest concerns related to additional operational activities and potential for technology failure. Health authorities’ feedback, through nonbinding meetings, was geographically varied; ethics committee feedback, through interviews, suggests concern over impact on operational process changes.ConclusionsWhile the appetite for eConsent is increasing, involved stakeholders and industry must continue to raise awareness, communicate, and collaborate to develop appropriate technological capabilities, regulatory pathways, and operational processes to clear the path for mainstream use of eConsent.

Forming and implementing community advisory boards in low- and middle-income countries: a scoping review

BackgroundCommunity advisory boards (CABs) have expanded beyond high-income countries (HICs) and play an increasing role in low- and middle-income country (LMIC) research. Much research has examined CABs in HICs, but less is known about CABs in LMICs. The purposes of this scoping review are to examine the creation and implementation of CABs in LMICs, including identifying frequently reported challenges, and to discuss implications for research ethics.MethodsWe searched five databases (PubMed, Embase, Global Health, Scopus, and Google Scholar) for publications describing or evaluating CABs in LMICs. Two researchers independently reviewed articles for inclusion. Data related to the following aspects of CABs were extracted from included publications: time, country, financial support, research focus, responsibilities, and challenges. Thematic analyses were used to summarize textual data describing challenges.ResultsOur search yielded 2005 citations, 83 of which were deemed eligible for inclusion. Most studies (65) were published between 2010 and 2017. Upper-middle-income countries were more likely to have studies describing CABs, with South Africa (17), China (8), and Thailand (7) having the greatest numbers. The United States National Institutes of Health was the main source of financial support for CABs. Many CABs (53/88, 60%) focused on HIV research. Thirty-four studies reported how CABs influenced the informed consent process for clinical trials or other aspects of research ethics. CAB responsibilities were related to clinical trials, including reviewing study protocols, educating local communities about research activities, and promoting the ethical conduct of research. Challenges faced by CABs included the following: incomplete ethical regulations and guidance; limited knowledge of science among members of communities and CABs; unstable and unbalanced power relationships between researchers and local communities; poor CAB management, including lack of formal participation structures and absence of CAB leadership; competing demands for time that limited participation in CAB activities; and language barriers between research staff and community members. Several challenges reflected shortcomings within the research team.ConclusionsOur findings examine the formation and implementation of CABs in LMICs and identify several ethical challenges. These findings suggest the need for further ethics training among CAB members and researchers in LMICs.

Facilitating the Informed Consent Process Using Teleconsent: Protocol for a Feasibility and Efficacy Study.

BackgroundInformed consent is among the biggest challenges in recruiting participants for clinical research studies. Researchers face many challenges in conducting clinical trials, some of which include budgetary restrictions, lack of trained personnel, and difficulty recruiting study participants—particularly minorities and participants from rural communities.ObjectiveThe objective of this study is to utilize telemedicine to improve the informed consent process for clinical trials and studies. We aim to assess the feasibility and efficacy of the teleconsent intervention among residents in urban and rural settings.MethodsThis study will be conducted separately yet concurrently at two institutions, the Medical University of South Carolina and the University of North Carolina at Chapel Hill, to compare results within and across institutions.ResultsEnrollment for Phase 1 began in March of 2018 and concluded in May 2018. Data transcription and analysis will be conducted through June and September of 2018.ConclusionsIn this paper, we present a novel approach for conducting informed consent using a new telemedicine modality, namely, teleconsent. Teleconsent presents the ability to conduct a live interaction among clinical research coordinators and potential participants while synchronously presenting the consent form on the screen and obtaining participant’s signature through doxy.me, the teleconsent system. Teleconsent provides potential to improve obtaining informed consent from potential clinical trial participants.Registered Report IdentifierRR1-10.2196/11239

Community advisory boards and research ethics in low-income and middle-income countries: a scoping review

BackgroundCommunity advisory boards (CABs) are no longer limited to high-income countries (HICs); they play an increasing role in research in low-income and middle-income countries (LMICs). Much work has examined the establishment and implementation of CABs in HICs, but less is known about CABs in LMICs. The purpose of this scoping review is to study the operation of CABs in LMICs and to discuss the implications for research ethics. MethodsWe searched five databases (PubMed, Embase, Global Health, Scopus, and Google Scholar) for publications describing or evaluating CABs in LMICs. Two researchers independently reviewed articles for inclusion. Data relating to the following aspects of CABs were extracted from included publications: publication date, country, financial support, research focus, responsibilities, and challenges. Thematic analyses were used to summarise textual data describing challenges. FindingsOur search yielded 2005 citations, 83 of which were deemed eligible for inclusion. Most studies (65) were published between 2010 and 2017. Upper-middle-income countries, as defined by the World Bank, were more likely to have CAB studies, and of these South Africa (17), China (8), and Thailand (7) had the greatest numbers. Among the 34 CABs whose funding sources were reported, the US National Institutes of Health was the main source of financial support for CABs. Most CABs (53 of 88) in our sample advised on HIV research. Thirty-four studies reported how CABs influenced the informed consent process for clinical trials or other aspects of research ethics. CAB responsibilities were related to clinical trials (87 of 88), including educating local communities about research activities, and promoting the ethical conduct of research. The challenges faced by CABs included incomplete ethical regulations and guidance, limited knowledge of science among CAB members, unstable and unbalanced power relationships between researchers and local communities, poor CAB management, competing demands for time that limited participation in CAB activities, and language barriers between research staff and community members. InterpretationCABs may be a useful instrument for increasing community engagement and improving the ethical conduct of research in LMICs. Our study identifies several challenges faced by CABs in LMICs. These findings can help inform training and related activities to enhance CABs in LMICs. FundingThis work was supported by the National Institutes of Health (National Institute of Allergy and Infectious Diseases [NIAID]) number 1R01A108366.

The Effect of Emotion on Visual Attention to Information and Decision Making in the Context of Informed Consent Process for Clinical Trials

AbstractThe aim of this study was to examine the influence of emotion on visual information processing and decision making in the context of informed consent. Researchers are ethically obligated to ensure informed consent in clinical trials; however, many volunteers have unrealistic expectations about the value of an experimental therapy. Moreover, suboptimal participation rates for clinical trials may be partially attributable to perceptions that ethical obligations to volunteers are not met. This study examines whether discrete negative emotions (fear, anger, and sadness) differentially influence information processing, visual attention, and decisions in the context of clinical trial informed consent. Community participants completed a standard emotion induction (or control) and then read an actual consent form from a clinical trial while eye movements were tracked. Fear and anger produced the most prominently different patterns of systematic processing and visual attention, such that fear induced longer fixations to information presented, whereas anger induced shorter fixations. Moreover, among women only, fear increased decisions to participate, compared with anger and neutral emotion. Examinations of associations between eye‐tracking variables and self‐reported outcomes indicated that for angry participants only, less systematic processing was associated with greater decisions to participate. Negative emotions of any kind decreased accurate perceptions of trial benefit. These patterns suggest a complex interplay among emotion, processing style, and decision making. Future research is necessary to further probe these effects among potential clinical trial volunteers. Published 2016. This article is a U.S Government work and is in the public domain in the USA.

Ensayos clínicos y consentimiento informado: visión de investigadores, pacientes y médicos de familia

ObjectiveAdequate information for patients and respect for their autonomy are mandatory in research. This article examined insights of researchers, patients and general practitioners (GPs) on the informed consent process in clinical trials, and the role of the GP. DesignA cross-sectional study using three questionnaires, informed consent reviews, medical records, and hospital discharge reports. SettingGPs, researchers and patients involved in clinical trials. ParticipantsIncluded, 504 GPs, 108 researchers, and 71 patients. ResultsConsulting the GP was recommended in 50% of the informed consents. Participation in clinical trials was shown in 33% of the medical records and 3% of the hospital discharge reports. GPs scored 3.54 points (on a 1-10 scale) on the assessment of the information received by the principal investigator. The readability of the informed consent sheet was rated 8.03 points by researchers, and the understanding was rated 7.68 points by patients. Patient satisfaction was positively associated with more time for reflection. ConclusionsGPs were not satisfied with the information received on the participation of patients under their in clinical trials. Researchers were satisfied with the information they offered to patients, and were aware of the need to improve the information GPs received. Patients collaborated greatly towards biomedical research, expressed satisfaction with the overall process, and minimised the difficulties associated with participation.

Newer Practice of Informed Consent Process of Clinical Trials in India

Informed consent encompasses imparting information related to risks, rights and benefits of participation to human participants in clinical research studies. This is followed by exercising the right to participate or not in the research study. Consent can be illicitly obtained by means of inducement, force, fraud, or other forms of coercion. Because of the lack of transparency in informed consent process in clinical trials, the Union Health Ministry of India has made audio-visual recording of the informed consent of each participant mandatory in 2013. This study aims to analyse the newly implemented practice of audio-visual recording of the informed consent process in clinical trials. It is a qualitative study based on an in-depth analytical description. The data included notes taken by the researcher and video recordings of the setting being studied. The new process appears to be a better documented process than that of written informed consent, with greater clarity of imparting relevant information of the trial. But elements of anonymity and confidentiality of trial participants, voluntariness in decision-making process and appropriateness of settings were found to be a few limitations of the process. It is necessary to get a better understanding of the challenges following implementation of the new policy in other parts of the country.

Decision aids for people considering taking part in clinical trials.

Several interventions have been developed to promote informed consent for participants in clinical trials. However, many of these interventions focus on the content and structure of information (e.g. enhanced information or changes to the presentation format) rather than the process of decision making. Patient decision aids support a decision making process about medical options. Decision aids support the decision process by providing information about available options and their associated outcomes, alongside information that enables patients to consider what value they place on particular outcomes, and provide structured guidance on steps of decision making. They have been shown to be effective for treatment and screening decisions but evidence on their effectiveness in the context of informed consent for clinical trials has not been synthesised. To assess the effectiveness of decision aids for clinical trial informed consent compared to no intervention, standard information (i.e. usual practice) or an alternative intervention on the decision making process. We searched the following databases and to March 2015: Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library; MEDLINE (OvidSP) (from 1950); EMBASE (OvidSP) (from 1980); PsycINFO (OvidSP) (from 1806); ASSIA (ProQuest) (from 1987); WHO International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch/); ClinicalTrials.gov; ISRCTN Register (http://www.controlled-trials.com/isrctn/). We also searched reference lists of included studies and relevant reviews. We contacted study authors and other experts. There were no language restrictions. We included randomised and quasi-randomised controlled trials comparing decision aids in the informed consent process for clinical trials alone, or in conjunction with standard information (such as written or verbal) or alongside alternative interventions (e.g. paper-based versus web-based decision aids). Included trials involved potential trial participants, or their guardians, being asked to consider participating in a real or hypothetical clinical trial. At least two authors independently assessed studies for inclusion, extracted reported data and assessed risk of bias. Findings were pooled where appropriate. We used GRADE to assess the quality of the evidence for each outcome. We identified one study (290 randomised participants) that investigated the effectiveness of decision aids compared to standard information in the informed consent process for clinical trials. This study reported two separate decision aid randomised controlled trials (RCTs). The decision aid trials were nested within two different parent trials focusing on breast cancer in postmenopausal women. One trial focused on informed consent for treatment in women who had previously had surgery for ductal carcinoma in situ (DCIS), the other on informed consent for prevention in women at high risk for breast cancer. Two different decision aids were used in these RCTs, and were compared with standard information.The pooled findings highlight the uncertainty surrounding most reported outcomes, including knowledge, decisional conflict, anxiety, trial participation and attrition. There was very low quality evidence that decision aids lower levels of decisional regret to a small degree (MD -5.53, 95% CI -10.29 to -0.76). No data were identified on several prespecified primary outcomes, including accurate risk perception, values-based decision, or whether potential participants recognised that a decision needed to be made, were able to identify features of options that matter most to individuals, or were involved in the decision. There was insufficient evidence to determine whether decision aids to support the informed consent process for clinical trials are more effective than standard information. Additional well designed, adequately powered clinical trials in more diverse clinical and social populations are needed to strengthen the results of this review. More generally, future research on which outcomes are most relevant for assessment in this context would be helpful.

Longitudinal study of informed consent in innovative therapy research: experience and provisional recommendations from a multicenter trial of intracerebral grafting.

BackgroundThere is an urgent need to assess and improve the consent process in clinical trials of innovative therapies for neurodegenerative disorders.MethodsWe performed a longitudinal study of the consent of Huntington’s disease patients during the Multicenter Fetal Cell Intracerebral Grafting Trial in Huntington’s Disease (MIG-HD) in France and Belgium. Patients and their proxies completed a consent questionnaire at inclusion, before signing the consent form and after one year of follow-up, before randomization and transplantation. The questionnaire explored understanding of the protocol, satisfaction with the information delivered, reasons for participating in the trial and expectations regarding the transplant. Forty-six Huntington’s disease patients and 27 proxies completed the questionnaire at inclusion, and 27 Huntington’s disease patients and 16 proxies one year later.ResultsThe comprehension score was high and similar for Huntington’s disease patients and proxies at inclusion (72.6% vs 77.8%; P > 0.1) but only decreased in HD patients after one year. The information satisfaction score was high (73.5% vs 66.5%; P > 0.1) and correlated with understanding in both patients and proxies. The motivation and expectation profiles were similar in patients and proxies and remained unchanged after one year.ConclusionsCognitively impaired patients with Huntington’s disease were capable of consenting to participation in this trial. This consent procedure has presumably strengthened their understanding and should be proposed before signing the consent form in future gene or cell therapy trials for neurodegenerative disorders. Because of the potential cognitive decline, proxies should be designated as provisional surrogate decision-makers, even in competent patients.

Evaluation of the Informed Consent Process of a Multicenter Tuberculosis Treatment Trial

Background: Ethical principles obligate researchers to maximize study participants’ comprehension during the informed consent process for clinical trials. A pilot evaluation of the consent process was conducted during an international clinical trial of treatment for pulmonary tuberculosis to assess the feasibility of conducting an evaluation in a larger population and to guide these future efforts. Methods: Study staff administered an informed consent assessment tool (ICAT) to a convenience sample of trial participants, measuring comprehension of consent components as derived from the Common Rule and FDA Title 21 Part 50, and satisfaction with the process. Participating site staff completed a consent process questionnaire about consent practices at their respective sites and provided improvement recommendations. ICAT scores and corresponding practices were compared where both were completed. Results: ICATs (n = 54) were submitted from one site in Spain (n = 10), one in Uganda (n = 30), and five in the United States (n = 14). Participants were primarily male (76%), born in Africa (n = 31, 57%), and had a median age of 27 years (interquartile range [IQR]: 24–42). Median ICAT scores were 80% (IQR: 67–93) for comprehension and 89% (IQR: 78–100) for satisfaction. Ugandan participants scored higher than participants from other sites on comprehension (87% vs. 64%) and satisfaction (100% vs. 78%). Staff from 14 sites completed consent process questionnaires. Median ICAT scores for comprehension and satisfaction were higher at sites that utilized visual aids. Practice recommendations included shorter forms, simpler documents, and supplementary materials. Conclusions: Participants achieved high levels (≥80%) of comprehension and satisfaction with their current consent processes. Higher ICAT scores at one site suggest an additional evaluation may identify approaches to improve comprehension and satisfaction in future trials. Through this pilot evaluation, complexities and challenges were identified in obtaining consent in a large, international multicenter trial and provided insights for a more robust assessment of the consent process in future trials.

Making a decision about trial participation: the feasibility of measuring deliberation during the informed consent process for clinical trials.

BackgroundInformed consent of trial participants is both an ethical and a legal requirement. When facing a decision about trial participation, potential participants are provided with information about the trial and have the opportunity to have any questions answered before their degree of ‘informed-ness’ is assessed, usually subjectively, and before they are asked to sign a consent form. Currently, standardised methods for assessing informed consent have tended to be focused on aspects of understanding and associated outcomes, rather than on the process of consent and the steps associated with decision-making.MethodsPotential trial participants who were approached regarding participation in one of three randomised controlled trials were asked to complete a short questionnaire to measure their deliberation about trial participation. A total of 136 participants completed the 10-item questionnaire (DelibeRATE) before they made an explicit decision about trial participation (defined as signing the clinical trial consent form). Overall DelibeRATE scores were compared and investigated for differences between trial consenters and refusers.ResultsNo differences in overall DelibeRATE scores were identified. In addition, there was no significant difference between overall score and the decision to participate, or not, in the parent trial.ConclusionsTo our knowledge, this is the first study to prospectively measure the deliberation stage of the informed consent decision-making process of potential trial participants across different conditions and clinical areas. Although there were no differences detected in overall scores or scores of trial consenters and refusers, we did identify some interesting findings. These findings should be taken into consideration by those designing trials and others interested in developing and implementing measures of potential trial participants decision making during the informed consent process for research.Trial registrationInternational Standard Randomised Controlled Trial Number (ISRCTN) Register ISRCTN60695184 (date of registration: 13 May 2009), ISRCTN80061723 (date of registration: 8 March 2010), ISRCTN69423238 (date of registration: 18 November 2010)

Parent ratings of ability to consent for clinical trials in fragile X syndrome.

Advances in understanding neurobiology and intellectual disabilities have led to clinical trials testing new medications. This study assessed parents' perceptions of the ability of their son or daughter with fragile X syndrome (FXS), an inherited form of intellectual disability, to participate in the consent process for clinical trials. Four hundred twenty-two families participated in a survey that included six items assessing various aspects of the ability to provide consent. A rank ordering of decisional tasks was found. The easiest task was to understand that the medication was different from his or her medical treatment; the most difficult was the ability to understand and weigh the potential benefits and risks of study participation. Factor analysis suggested that despite the range in difficulty, the six items were best summarized by a single decisional ability score. Parents of 29% of males reported that their son was not at all capable of participating, but the remainder exhibited a range of decisional skills. Factors associated with this variability include age and parents' willingness to enroll their child in clinical trials. We conclude that many individuals with FXS appear to be able to participate at some level in the consent or assent process, but will likely need individualized support to maximize effective participation.

Audio-visual presentation of information for informed consent for participation in clinical trials.

Informed consent is a critical component of clinical research. Different methods of presenting information to potential participants of clinical trials may improve the informed consent process. Audio-visual interventions (presented, for example, on the Internet or on DVD) are one such method. We updated a 2008 review of the effects of these interventions for informed consent for trial participation. To assess the effects of audio-visual information interventions regarding informed consent compared with standard information or placebo audio-visual interventions regarding informed consent for potential clinical trial participants, in terms of their understanding, satisfaction, willingness to participate, and anxiety or other psychological distress. We searched: the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, issue 6, 2012; MEDLINE (OvidSP) (1946 to 13 June 2012); EMBASE (OvidSP) (1947 to 12 June 2012); PsycINFO (OvidSP) (1806 to June week 1 2012); CINAHL (EbscoHOST) (1981 to 27 June 2012); Current Contents (OvidSP) (1993 Week 27 to 2012 Week 26); and ERIC (Proquest) (searched 27 June 2012). We also searched reference lists of included studies and relevant review articles, and contacted study authors and experts. There were no language restrictions. We included randomised and quasi-randomised controlled trials comparing audio-visual information alone, or in conjunction with standard forms of information provision (such as written or verbal information), with standard forms of information provision or placebo audio-visual information, in the informed consent process for clinical trials. Trials involved individuals or their guardians asked to consider participating in a real or hypothetical clinical study. (In the earlier version of this review we only included studies evaluating informed consent interventions for real studies). Two authors independently assessed studies for inclusion and extracted data. We synthesised the findings using meta-analysis, where possible, and narrative synthesis of results. We assessed the risk of bias of individual studies and considered the impact of the quality of the overall evidence on the strength of the results. We included 16 studies involving data from 1884 participants. Nine studies included participants considering real clinical trials, and eight included participants considering hypothetical clinical trials, with one including both. All studies were conducted in high-income countries.There is still much uncertainty about the effect of audio-visual informed consent interventions on a range of patient outcomes. However, when considered across comparisons, we found low to very low quality evidence that such interventions may slightly improve knowledge or understanding of the parent trial, but may make little or no difference to rate of participation or willingness to participate. Audio-visual presentation of informed consent may improve participant satisfaction with the consent information provided. However its effect on satisfaction with other aspects of the process is not clear. There is insufficient evidence to draw conclusions about anxiety arising from audio-visual informed consent. We found conflicting, very low quality evidence about whether audio-visual interventions took more or less time to administer. No study measured researcher satisfaction with the informed consent process, nor ease of use.The evidence from real clinical trials was rated as low quality for most outcomes, and for hypothetical studies, very low. We note, however, that this was in large part due to poor study reporting, the hypothetical nature of some studies and low participant numbers, rather than inconsistent results between studies or confirmed poor trial quality. We do not believe that any studies were funded by organisations with a vested interest in the results. The value of audio-visual interventions as a tool for helping to enhance the informed consent process for people considering participating in clinical trials remains largely unclear, although trends are emerging with regard to improvements in knowledge and satisfaction. Many relevant outcomes have not been evaluated in randomised trials. Triallists should continue to explore innovative methods of providing information to potential trial participants during the informed consent process, mindful of the range of outcomes that the intervention should be designed to achieve, and balancing the resource implications of intervention development and delivery against the purported benefits of any intervention.More trials, adhering to CONSORT standards, and conducted in settings and populations underserved in this review, i.e. low- and middle-income countries and people with low literacy, would strengthen the results of this review and broaden its applicability. Assessing process measures, such as time taken to administer the intervention and researcher satisfaction, would inform the implementation of audio-visual consent materials.

Exploring research participants’ perceptions and comprehension of the informed consent process in a pre-exposure HIV prevention study: a case study

Background Ensuring informed consent is a complicated component of clinical trials particularly with HIV prevention trials conducted in resource-limited settings. An inherent challenge of the informed consent process for HIV prevention studies is making sure trial participants understand that their participation does not increase exposure to HIV. Participants need to comprehend that partaking in such trials does not necessarily protect them from HIV. It is important to continuously monitor the informed consent process for clinical trials with view to improving the procedure.