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1.  What is the role and authority of gatekeepers in cluster randomized trials in health research? 
Trials  2012;13:116.
This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the CRT is to be set on a firm ethical foundation. This paper addresses the sixth of the questions posed, namely, what is the role and authority of gatekeepers in CRTs in health research? ‘Gatekeepers’ are individuals or bodies that represent the interests of cluster members, clusters, or organizations. The need for gatekeepers arose in response to the difficulties in obtaining informed consent because of cluster randomization, cluster-level interventions, and cluster size. In this paper, we call for a more restrictive understanding of the role and authority of gatekeepers.
Previous papers in this series have provided solutions to the challenges posed by informed consent in CRTs without the need to invoke gatekeepers. We considered that consent to randomization is not required when cluster members are approached for consent at the earliest opportunity and before any study interventions or data-collection procedures have started. Further, when cluster-level interventions or cluster size means that obtaining informed consent is not possible, a waiver of consent may be appropriate. In this paper, we suggest that the role of gatekeepers in protecting individual interests in CRTs should be limited. Generally, gatekeepers do not have the authority to provide proxy consent for cluster members. When a municipality or other community has a legitimate political authority that is empowered to make such decisions, cluster permission may be appropriate; however, gatekeepers may usefully protect cluster interests in other ways. Cluster consultation may ensure that the CRT addresses local health needs, and is conducted in accord with local values and customs. Gatekeepers may also play an important role in protecting the interests of organizations, such as hospitals, nursing homes, general practices, and schools. In these settings, permission to access the organization relies on resource implications and adherence to institutional policies.
PMCID: PMC3443001  PMID: 22834691
2.  Does clinical equipoise apply to cluster randomized trials in health research? 
Trials  2011;12:118.
This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, Weijer and colleagues set out six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation. This paper addresses the third of the questions posed, namely, does clinical equipoise apply to CRTs in health research? The ethical principle of beneficence is the moral obligation not to harm needlessly and, when possible, to promote the welfare of research subjects. Two related ethical problems have been discussed in the CRT literature. First, are control groups that receive only usual care unduly disadvantaged? Second, when accumulating data suggests the superiority of one intervention in a trial, is there an ethical obligation to act?
In individually randomized trials involving patients, similar questions are addressed by the concept of clinical equipoise, that is, the ethical requirement that, at the start of a trial, there be a state of honest, professional disagreement in the community of expert practitioners as to the preferred treatment. Since CRTs may not involve physician-researchers and patient-subjects, the applicability of clinical equipoise to CRTs is uncertain. Here we argue that clinical equipoise may be usefully grounded in a trust relationship between the state and research subjects, and, as a result, clinical equipoise is applicable to CRTs. Clinical equipoise is used to argue that control groups receiving only usual care are not disadvantaged so long as the evidence supporting the experimental and control interventions is such that experts would disagree as to which is preferred. Further, while data accumulating during the course of a CRT may favor one intervention over another, clinical equipoise supports continuing the trial until the results are likely to be broadly convincing, often coinciding with the planned completion of the trial. Finally, clinical equipoise provides research ethics committees with formal and procedural guidelines that form an important part of the assessment of the benefits and harms of CRTs in health research.
PMCID: PMC3113987  PMID: 21569349
3.  Ethical issues posed by cluster randomized trials in health research 
Trials  2011;12:100.
The cluster randomized trial (CRT) is used increasingly in knowledge translation research, quality improvement research, community based intervention studies, public health research, and research in developing countries. However, cluster trials raise difficult ethical issues that challenge researchers, research ethics committees, regulators, and sponsors as they seek to fulfill responsibly their respective roles. Our project will provide a systematic analysis of the ethics of cluster trials. Here we have outlined a series of six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation:
1. Who is a research subject?
2. From whom, how, and when must informed consent be obtained?
3. Does clinical equipoise apply to CRTs?
4. How do we determine if the benefits outweigh the risks of CRTs?
5. How ought vulnerable groups be protected in CRTs?
6. Who are gatekeepers and what are their responsibilities?
Subsequent papers in this series will address each of these areas, clarifying the ethical issues at stake and, where possible, arguing for a preferred solution. Our hope is that these papers will serve as the basis for the creation of international ethical guidelines for the design and conduct of cluster randomized trials.
PMCID: PMC3107798  PMID: 21507237
4.  Researchers’ perceptions of ethical challenges in cluster randomized trials: a qualitative analysis 
Trials  2013;14:1.
Cluster randomized trials (CRTs) pose ethical challenges for investigators and ethics committees. This study describes the views and experiences of CRT researchers with respect to: (1) ethical challenges in CRTs; (2) the ethics review process for CRTs; and (3) the need for comprehensive ethics guidelines for CRTs.
Descriptive qualitative analysis of interviews conducted with a purposive sample of 20 experienced CRT researchers.
Informants expressed concern over the potential for bias that may result from requirements to obtain informed consent from research participants in CRTs. Informants suggested that the need for informed consent ought to be related to the type of intervention under study in a CRT. Informants rarely expressed concern regarding risks to research participants in CRTs, other than risks to privacy. Important issues identified in the research ethics literature, including fair subject selection and other justice issues, were not mentioned by informants. The ethics review process has had positive and negative impacts on CRT conduct. Informants stated that variability in ethics review between jurisdictions, and increasingly stringent ethics review in recent years, have hampered their ability to conduct CRTs. Many informants said that comprehensive ethics guidelines for CRTs would be helpful to researchers and research ethics committees.
Informants identified key ethical challenges in the conduct of CRTs, specifically relating to identifying subjects, seeking informed consent, and the use of gatekeepers. These data have since been used to identify topics for in-depth ethical analysis and to guide the development of comprehensive ethics guidelines for CRTs.
PMCID: PMC3561139  PMID: 23286245
Cluster randomized trials; Research ethics; Informed consent; Clinical trials; Bioethics; Knowledge translation; Quality improvement; Implementation research
5.  Who is the research subject in cluster randomized trials in health research? 
Trials  2011;12:183.
This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the CRT is to be set on a firm ethical foundation. This paper addresses the first of the questions posed, namely, who is the research subject in a CRT in health research? The identification of human research subjects is logically prior to the application of protections as set out in research ethics and regulation. Aspects of CRT design, including the fact that in a single study the units of randomization, experimentation, and observation may differ, complicate the identification of human research subjects. But the proper identification of human research subjects is important if they are to be protected from harm and exploitation, and if research ethics committees are to review CRTs efficiently.
We examine the research ethics literature and international regulations to identify the core features of human research subjects, and then unify these features under a single, comprehensive definition of human research subject. We define a human research subject as any person whose interests may be compromised as a result of interventions in a research study. Individuals are only human research subjects in CRTs if: (1) they are directly intervened upon by investigators; (2) they interact with investigators; (3) they are deliberately intervened upon via a manipulation of their environment that may compromise their interests; or (4) their identifiable private information is used to generate data. Individuals who are indirectly affected by CRT study interventions, including patients of healthcare providers participating in knowledge translation CRTs, are not human research subjects unless at least one of these conditions is met.
PMCID: PMC3162904  PMID: 21791064
6.  Participant Informed Consent in Cluster Randomized Trials: Review 
PLoS ONE  2012;7(7):e40436.
The Nuremberg code defines the general ethical framework of medical research with participant consent as its cornerstone. In cluster randomized trials (CRT), obtaining participant informed consent raises logistic and methodologic concerns. First, with randomization of large clusters such as geographical areas, obtaining individual informed consent may be impossible. Second, participants in randomized clusters cannot avoid certain interventions, which implies that participant informed consent refers only to data collection, not administration of an intervention. Third, complete participant information may be a source of selection bias, which then raises methodological concerns. We assessed whether participant informed consent was required in such trials, which type of consent was required, and whether the trial was at risk of selection bias because of the very nature of participant information.
Methods and Findings
We systematically reviewed all reports of CRT published in MEDLINE in 2008 and surveyed corresponding authors regarding the nature of the informed consent and the process of participant inclusion. We identified 173 reports and obtained an answer from 113 authors (65.3%). In total, 23.7% of the reports lacked information on ethics committee approval or participant consent, 53.1% of authors declared that participant consent was for data collection only and 58.5% that the group allocation was not specified for participants. The process of recruitment (chronology of participant recruitment with regard to cluster randomization) was rarely reported, and we estimated that only 56.6% of the trials were free of potential selection bias.
For CRTs, the reporting of ethics committee approval and participant informed consent is less than optimal. Reports should describe whether participants consented for administration of an intervention and/or data collection. Finally, the process of participant recruitment should be fully described (namely, whether participants were informed of the allocation group before being recruited) for a better appraisal of the risk of selection bias.
PMCID: PMC3391275  PMID: 22792319
7.  Ethical issues in implementation research: a discussion of the problems in achieving informed consent 
Improved quality of care is a policy objective of health care systems around the world. Implementation research is the scientific study of methods to promote the systematic uptake of clinical research findings into routine clinical practice, and hence to reduce inappropriate care. It includes the study of influences on healthcare professionals' behaviour and methods to enable them to use research findings more effectively. Cluster randomized trials represent the optimal design for evaluating the effectiveness of implementation strategies. Various codes of medical ethics, such as the Nuremberg Code and the Declaration of Helsinki inform medical research, but their relevance to cluster randomised trials in implementation research is unclear. This paper discusses the applicability of various ethical codes to obtaining consent in cluster trials in implementation research.
The appropriate application of biomedical codes to implementation research is not obvious. Discussion of the nature and practice of informed consent in implementation research cluster trials must consider the levels at which consent can be sought, and for what purpose it can be sought. The level at which an intervention is delivered can render the idea of patient level consent meaningless. Careful consideration of the ownership of information, and rights of access to and exploitation of data is required. For health care professionals and organizations, there is a balance between clinical freedom and responsibility to participate in research.
While ethical justification for clinical trials relies heavily on individual consent, for implementation research aspects of distributive justice, economics, and political philosophy underlie the debate. Societies may need to trade off decisions on the choice between individualized consent and valid implementation research. We suggest that social sciences codes could usefully inform the consideration of implementation research by members of Research Ethics Committees.
PMCID: PMC2639614  PMID: 19091100
8.  Strategies for Increasing Recruitment to Randomised Controlled Trials: Systematic Review 
PLoS Medicine  2010;7(11):e1000368.
Patrina Caldwell and colleagues performed a systematic review of randomized studies that compared methods of recruiting individual study participants into trials, and found that strategies that focus on increasing potential participants' awareness of the specific health problem, and that engaged them, appeared to increase recruitment.
Recruitment of participants into randomised controlled trials (RCTs) is critical for successful trial conduct. Although there have been two previous systematic reviews on related topics, the results (which identified specific interventions) were inconclusive and not generalizable. The aim of our study was to evaluate the relative effectiveness of recruitment strategies for participation in RCTs.
Methods and Findings
A systematic review, using the PRISMA guideline for reporting of systematic reviews, that compared methods of recruiting individual study participants into an actual or mock RCT were included. We searched MEDLINE, Embase, The Cochrane Library, and reference lists of relevant studies. From over 16,000 titles or abstracts reviewed, 396 papers were retrieved and 37 studies were included, in which 18,812 of at least 59,354 people approached agreed to participate in a clinical RCT. Recruitment strategies were broadly divided into four groups: novel trial designs (eight studies), recruiter differences (eight studies), incentives (two studies), and provision of trial information (19 studies). Strategies that increased people's awareness of the health problem being studied (e.g., an interactive computer program [relative risk (RR) 1.48, 95% confidence interval (CI) 1.00–2.18], attendance at an education session [RR 1.14, 95% CI 1.01–1.28], addition of a health questionnaire [RR 1.37, 95% CI 1.14–1.66]), or a video about the health condition (RR 1.75, 95% CI 1.11–2.74), and also monetary incentives (RR1.39, 95% CI 1.13–1.64 to RR 1.53, 95% CI 1.28–1.84) improved recruitment. Increasing patients' understanding of the trial process, recruiter differences, and various methods of randomisation and consent design did not show a difference in recruitment. Consent rates were also higher for nonblinded trial design, but differential loss to follow up between groups may jeopardise the study findings. The study's main limitation was the necessity of modifying the search strategy with subsequent search updates because of changes in MEDLINE definitions. The abstracts of previous versions of this systematic review were published in 2002 and 2007.
Recruitment strategies that focus on increasing potential participants' awareness of the health problem being studied, its potential impact on their health, and their engagement in the learning process appeared to increase recruitment to clinical studies. Further trials of recruitment strategies that target engaging participants to increase their awareness of the health problems being studied and the potential impact on their health may confirm this hypothesis.
Please see later in the article for the Editors' Summary
Editors' Summary
Before any health care intervention—a treatment for a disease or a measure such as vaccination that is designed to prevent an illness—is adopted by the medical community, it undergoes exhaustive laboratory-based and clinical research. In the laboratory, scientists investigate the causes of diseases, identify potential new treatments or preventive methods, and test these interventions in animals. New interventions that look hopeful are then investigated in clinical trials—studies that test these interventions in people by following a strict trial protocol or action plan. Phase I trials test interventions in a few healthy volunteers or patients to evaluate their safety and to identify possible side effects. In phase II trials, a larger group of patients receives an intervention to evaluate its safety further and to get an initial idea of its effectiveness. In phase III trials, very large groups of patients (sometimes in excess of a thousand people) are randomly assigned to receive the new intervention or an established intervention or placebo (dummy intervention). These “randomized controlled trials” or “RCTs” provide the most reliable information about the effectiveness and safety of health care interventions.
Why Was This Study Done?
Patients who participate in clinical trials must fulfill the inclusion criteria laid down in the trial protocol and must be given information about the trial, its risks, and potential benefits before agreeing to participate (informed consent). Unfortunately, many RCTs struggle to enroll the number of patients specified in their trial protocol, which can reduce a trial's ability to measure the effect of a new intervention. Inadequate recruitment can also increase costs and, in the worst cases, prevent trial completion. Several strategies have been developed to improve recruitment but it is not clear which strategy works best. In this study, the researchers undertake a systematic review (a study that uses predefined criteria to identify all the research on a given topic) of “recruitment trials”—studies that have randomly divided potential RCT participants into groups, applied different strategies for recruitment to each group, and compared recruitment rates in the groups.
What Did the Researchers Do and Find?
The researchers identified 37 randomized trials of recruitment strategies into real and mock RCTs (where no actual trial occurred). In all, 18,812 people agreed to participate in an RCT in these recruitment trials out of at least 59,354 people approached. Some of these trials investigated novel strategies for recruitment, such as changes in how patients are randomized. Others looked at the effect of recruiter differences (for example, increased contact between the health care professionals doing the recruiting and the trial investigators), the effect of offering monetary incentives to participants, and the effect of giving more information about the trial to potential participants. Recruitment strategies that improved people's awareness of the health problem being studied—provision of an interactive computer program or a video about the health condition, attendance at an educational session, or inclusion of a health questionnaire in the recruitment process—improved recruitment rates, as did monetary incentives. Increasing patients' understanding about the trial process itself, recruiter differences, and alterations in consent design and randomization generally had no effect on recruitment rates although consent rates were higher when patients knew the treatment to which they had been randomly allocated before consenting. However, differential losses among the patients in different treatment groups in such nonblinded trials may jeopardize study findings.
What Do These Findings Mean?
These findings suggest that trial recruitment strategies that focus on increasing the awareness of potential participants of the health problem being studied and its possible effects on their health, and that engage potential participants in the trial process are likely to increase recruitment to RCTs. The accuracy of these findings depends on whether the researchers identified all the published research on recruitment strategies and on whether other research on recruitment strategies has been undertaken and not published that could alter these findings. Furthermore, because about half of the recruitment trials identified by the researchers were undertaken in the US, the successful strategies identified here might not be generalizable to other countries. Nevertheless, these recruitment strategies should now be investigated further to ensure that the future evaluation of new health care interventions is not hampered by poor recruitment into RCTs.
Additional Information
Please access these Web sites via the online version of this summary at
The Web site is a searchable register of federally and privately supported clinical trials in the US and around the world, providing information about all aspects of clinical trials
The US National Institutes of Health provides information about clinical trials
The UK National Health Service Choices Web site has information for patients about clinical trials and medical research
The UK Medical Research Council Clinical Trials Units also provides information for patients about clinical trials and links to information on clinical trials provided by other organizations
MedlinePlus has links to further resources on clinical trials (in English and Spanish)
The Australian Government's National Health and Medical Research Council has information about clinical trials
WHO International Clinical Trials Registry Platform aims to ensure that all trials are publicly accessible to those making health care decisions
The Star Child Health International Forum of Standards for Research is a resource center for pediatric clinical trial design, conduct, and reporting
PMCID: PMC2976724  PMID: 21085696
9.  Variability in research ethics review of cluster randomized trials: a scenario-based survey in three countries 
Trials  2014;15:48.
Cluster randomized trials (CRTs) present unique ethical challenges. In the absence of a uniform standard for their ethical design and conduct, problems such as variability in procedures and requirements by different research ethics committees will persist. We aimed to assess the need for ethics guidelines for CRTs among research ethics chairs internationally, investigate variability in procedures for research ethics review of CRTs within and among countries, and elicit research ethics chairs’ perspectives on specific ethical issues in CRTs, including the identification of research subjects. The proper identification of research subjects is a necessary requirement in the research ethics review process, to help ensure, on the one hand, that subjects are protected from harm and exploitation, and on the other, that reviews of CRTs are completed efficiently.
A web-based survey with closed- and open-ended questions was administered to research ethics chairs in Canada, the United States, and the United Kingdom. The survey presented three scenarios of CRTs involving cluster-level, professional-level, and individual-level interventions. For each scenario, a series of questions was posed with respect to the type of review required (full, expedited, or no review) and the identification of research subjects at cluster and individual levels.
A total of 189 (35%) of 542 chairs responded. Overall, 144 (84%, 95% CI 79 to 90%) agreed or strongly agreed that there is a need for ethics guidelines for CRTs and 158 (92%, 95% CI 88 to 96%) agreed or strongly agreed that research ethics committees could be better informed about distinct ethical issues surrounding CRTs. There was considerable variability among research ethics chairs with respect to the type of review required, as well as the identification of research subjects. The cluster-cluster and professional-cluster scenarios produced the most disagreement.
Research ethics committees identified a clear need for ethics guidelines for CRTs and education about distinct ethical issues in CRTs. There is disagreement among committees, even within the same countries, with respect to key questions in the ethics review of CRTs. This disagreement reflects variability of opinion and practices pointing toward possible gaps in knowledge, and supports the need for explicit guidelines for the ethical conduct and review of CRTs.
PMCID: PMC3925119  PMID: 24495542
Cluster randomized trials; Informed consent; Research ethics guidelines; Research ethics review; Web-based survey
10.  Inadequate reporting of research ethics review and informed consent in cluster randomised trials: review of random sample of published trials 
Objectives To investigate the extent to which authors of cluster randomised trials adhered to two basic requirements of the World Medical Association’s Declaration of Helsinki and the International Committee of Medical Journal Editors’ uniform requirements for manuscripts (namely, reporting of research ethics review and informed consent), to determine whether the adequacy of reporting has improved over time, and to identify characteristics of cluster randomised trials associated with reporting of ethics practices.
Design Review of a random sample of published cluster randomised trials from an electronic search in Medline.
Setting Cluster randomised trials in health research published in English language journals from 2000 to 2008.
Study sample 300 cluster randomised trials published in 150 journals.
Results 77 (26%, 95% confidence interval 21% to 31%) trials failed to report ethics review. The proportion reporting ethics review increased significantly over time (P<0.001). Trials with data collection interventions at the individual level were more likely to report ethics review than were trials that used routine data sources only (79% (n=151) v 55% (23); P=0.008). Trials that accounted for clustering in the design and analysis were more likely to report ethics review. The median impact factor of the journal of publication was higher for trials that reported ethics review (3.4 v 2.3; P<0.001). 93 (31%, 26% to 36%) trials failed to report consent. Reporting of consent increased significantly over time (P<0.001). Trials with interventions targeting participants at the individual level were more likely to report consent than were trials with interventions targeting the cluster level (87% (90) v 48% (41); P<0.001). Trials with data collection interventions at the individual level were more likely to report consent than were those that used routine data sources only (78% (146) v 29% (11); P<0.001).
Conclusions Reporting of research ethics protections in cluster randomised trials is inadequate. In addition to research ethics approval, authors should report whether informed consent was sought, from whom consent was sought, and what consent was for.
PMCID: PMC3092521  PMID: 21562003
11.  Use of deferred consent for severely ill children in a multi-centre phase III trial 
Trials  2011;12:90.
Voluntary participation of a subject in research respects a subject's rights, strengthens its ethical conduct, and is formalized by the informed consent process. Clinical trials of life-saving interventions for medical emergencies often necessitate enrolment of patients where prior written individual informed consent is impossible. Although there are regulations and guidelines on protecting subjects in emergency research, these have been criticised for being limited and unnecessarily restrictive. Across Europe and the United States stringent regulations have resulted in a substantial decline of clinical trials involving emergency interventions.
We are conducting a trial of fluid resuscitation in children with hypovolaemic shock in six hospitals across three malaria-endemic African countries. The design is pragmatic as children are enrolled on clinical criteria alone and is being conducted in hospitals with facilities typical of many district hospitals across Africa. The trial aims to inform strategy for managing children with febrile illness and features of shock. In order to develop appropriate consent processes for the trial, we conducted a narrative review of current international recommendations for emergency consent.
Practical or specific guidance was generally sparse or confusing with few examples in the literature to direct our informed consent process. For a sub-group of children who were critically sick or where parents themselves were otherwise too distressed to consider prior written consent, we opted for a modified form of deferred consent. This included verbal assent from guardians at the point of enrolment, with full written consent obtained after stabilising the child. For children who died prior to full written consent, ethical permission was received to waiver full consent.
In light of the controversy around guidance and regulations in this area we report how and why we have used a modified system of deferred consent in an emergency intervention trial in children. Although approved by all relevant ethics committees and operational in 3 countries in Africa, formal research is now necessary to explore the perceptions and experiences of parents, health workers, researchers and ethics committees of the modified method of deferred consent.
PMCID: PMC3077324  PMID: 21453454
12.  Knowledge & attitudes of mental health professionals regarding psychiatric research 
Background & objectives:
Mental health professionals have varied attitudes and views regarding informed consent and confidentiality protections in psychiatric research and clinical care. The present study was designed to understand the knowledge and views of mental health professionals (MHPs) regarding informed consent and confidentiality protection practices.
Mental health professionals (n=121) who were members of the Delhi Psychiatric Society, were invited to participate in this questionnaire-based study of their knowledge and attitudes regarding informed consent and confidentiality. Half of them expressed willingness to discuss participation and gave initial oral consent (n=62); of these, 31 gave written informed consent to participate and completed the questionnaires. The questionnaires included both forced choice (yes / no / do not know) and open-ended questions. Questionnaires content reflected prominent guidelines on informed consent and confidentiality protection.
Attitudes of the majority of the participants towards informed consent and confidentiality were in line with ethical principles and guidelines. All expressed the opinion that confidentiality should generally be respected and that if confidentiality was breached, there could be mistrust of the professional by the patient/participant. The mean knowledge scores regarding informed consent and confidentiality were 8.55 ± 1.46 and 8.16 ± 1.29, respectively.
Interpretation & conclusions:
The participating mental health professionals appeared to have adequate knowledge of basic ethical guidelines concerning informed consent and confidentiality. Most respondents were aware of ethical issues in research. Given the small sample size and low response rate, the significance of the quantitative analysis must be regarded with modesty, and qualitative analysis of open-ended questions may be more valuable for development of future research. Increased efforts to involve mental health professionals in research on ethical concerns pertinent to their work must be made, and the actual practices of these professionals with regard to ethical guidelines need to be studied.
PMCID: PMC4001336  PMID: 24718399
Confidentiality; ethical guidelines; informed consent; mental health professionals; mental health research
13.  Randomization to Standard and Concise Informed Consent Forms: Development of Evidence-Based Consent Practices 
Contemporary clinical trials  2012;33(5):895-902.
Consent to participate in research is an important component of the conduct of ethical clinical trials. Current consent practices are largely policy-driven. This study was conducted to assess comprehension of study information and satisfaction with the consent form between subjects randomized to concise or to standard informed consent forms as one approach to developing evidence-based consent practices.
Participants (N=111) who enrolled into two Phase I investigational influenza vaccine protocols (VRC 306 and VRC 307) at the NIH Clinical Center were randomized to one of two IRB-approved consents; either a standard or concise form. Concise consents had an average of 63% fewer words. All other aspects of the consent process were the same. Questionnaires about the study and the consent process were completed at enrollment and at the last visit in both studies.
Subjects using concise consent forms scored as well as those using standard length consents in measures of comprehension (7 versus 7, p=0.79 and 20 versus 21, p=0.13), however, the trend was for the concise consent group to report feeling better informed. Both groups thought the length and detail of the consent form was appropriate.
Randomization of study subjects to different length IRB-approved consents forms as one method for developing evidence-based consent practices, resulted in no differences in study comprehension or satisfaction with the consent form. A concise consent form may be used ethically in the context of a consent process conducted by well-trained staff with opportunities for discussion and education throughout the study.
PMCID: PMC3408575  PMID: 22542645
clinical trial; informed consent; Institutional Review Board; comprehension; research subject
14.  The Ethical Odyssey in Testing HIV Treatment as Prevention 
Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HPTN 052, the multinational clinical trial addressing this issue that has profound public health implications.
To describe and analyze the major ethical challenges faced in HPTN 052.
The ethical issues and modifications of HPTN 052 in response to these issues were catalogued by the principal investigator, the lead coordinator, and the ethicist working on the trial. The major ethical issues that were unique to the trial were then described and analyzed, referring as appropriate to published literature and emerging guidance and policies. Ethical challenges that must be addressed in many clinical trials, such as those related to obtaining informed consent and making provisions for ancillary care, are not described.
When HPTN 052 was being designed, ethical questions emerged related to the relevance of the research question itself given data from observational research and a range of beliefs about the appropriate means of preventing and treating HIV-infection and AIDS. Further, ethical challenges were faced regarding site selection since there was a scientific need to conduct the research in settings where HIV incidence was high, but alternatives to study participation should be available. As in most HIV prevention research, ethical questions surrounded the determination of the appropriate prevention package for all of those enrolled. During the course of the trial, guidance documents and policies emerged that were of direct relevance to the research questions, calling for a balancing of concerns for the research subjects and trial integrity. When the study results were made public, there was a need to ensure access to the treatment shown to be effective that in some cases differed from the guidelines used at the sites where the research was being conducted. In addition, questions were raised about whether there was an obligation to notify subjects about “unlinked’ transmissions of HIV, that is, infections acquired outside of the designated sexual partners enrolled in the study.
The ethical issues described are limited to those discerned by the authors and not those of other stakeholders who may have identified additional issues or had a different perspective in analyzing them.
Understanding the ethical challenges faced in HPTN 052 promises to inform the design and conduct of future complex, long-term clinical trials aimed at addressing critical scientific and public health questions, where data and practice patterns emerge over the course of the trial.
PMCID: PMC3486723  PMID: 22692805
15.  Challenges for consent and community engagement in the conduct of cluster randomized trial among school children in low income settings: experiences from Kenya 
Trials  2013;14:142.
There are a number of practical and ethical issues raised in school-based health research, particularly those related to obtaining consent from parents and assent from children. One approach to developing, strengthening, and supporting appropriate consent and assent processes is through community engagement. To date, much of the literature on community engagement in biomedical research has concentrated on community- or hospital-based research, with little documentation, if any, of community engagement in school-based health research. In this paper we discuss our experiences of consent, assent and community engagement in implementing a large school-based cluster randomized trial in rural Kenya.
Data collected as part of a qualitative study investigating the acceptability of the main trial, focus group discussions with field staff, observations of practice and authors’ experiences are used to: 1) highlight the challenges faced in obtaining assent/consent; and 2) strategies taken to try to both protect participant rights (including to refuse and to withdraw) and ensure the success of the trial.
Early meetings with national, district and local level stakeholders were important in establishing their co-operation and support for the project. Despite this support, both practical and ethical challenges were encountered during consenting and assenting procedures. Our strategy for addressing these challenges focused on improving communication and understanding of the trial, and maintaining dialogue with all the relevant stakeholders throughout the study period.
A range of stakeholders within and beyond schools play a key role in school based health trials. Community entry and information dissemination strategies need careful planning from the outset, and with on-going consultation and feedback mechanisms established in order to identify and address concerns as they arise. We believe our experiences, and the ethical and practical issues and dilemmas encountered, will be of interest for others planning to conduct school-based research in Africa.
Trial registration
National Institute of Health NCT00878007
PMCID: PMC3661351  PMID: 23680181
Malaria; Cluster-randomized trial; Consent; Community engagement; School-based research; Kenya
16.  Tailoring Consent to Context: Designing an Appropriate Consent Process for a Biomedical Study in a Low Income Setting 
Currently there is increasing recognition of the need for research in developing countries where disease burden is high. Understanding the role of local factors is important for undertaking ethical research in developing countries. We explored factors relating to information and communication during the process of informed consent, and the approach that should be followed for gaining consent. The study was conducted prior to a family-based genetic study among people with podoconiosis (non-filarial elephantiasis) in southern Ethiopia.
Methodology/Principal Findings
We adapted a method of rapid assessment validated in The Gambia. The methodology was entirely qualitative, involving focus-group discussions and in-depth interviews. Discussions were conducted with podoconiosis patients and non-patients in the community, fieldworkers, researchers, staff of the local non-governmental organisation (NGO) working on prevention and treatment of podoconiosis, and community leaders. We found that the extent of use of everyday language, the degree to which expectations of potential participants were addressed, and the techniques of presentation of information had considerable impact on comprehension of information provided about research. Approaching podoconiosis patients via locally trusted individuals and preceding individual consent with community sensitization were considered the optimal means of communication. Prevailing poverty among podoconiosis patients, the absence of alternative treatment facilities, and participants' trust in the local NGO were identified as potential barriers for obtaining genuine informed consent.
Researchers should evaluate the effectiveness of consent processes in providing appropriate information in a comprehensible manner and in supporting voluntary decision-making on a study-by-study basis.
Author Summary
Informed consent to biomedical research in developing countries is a highly topical issue. When consent forms and processes are simply borrowed from developed countries, obtaining genuine informed consent becomes extremely challenging. This paper examines how a quick and relatively simple intervention (Rapid Assessment) can influence the design and implementation of informed consent processes in the context of biomedical research involving poor, socially stigmatized and illiterate communities in a developing country. The paper goes on to discuss the effect of social, cultural, and economic factors identified by the intervention in a particular context and demonstrates how knowledge of these influences helped to develop a socially relevant and practical consent process prior to conducting a programme of community-based genetic research. The paper concludes that this intervention is an effective and economical means by which to ensure the efficacy and ethical integrity of consent processes when recruiting participants to new research sites, even within countries with which researchers are already acquainted.
PMCID: PMC2705797  PMID: 19621067
17.  Evaluation of the quality of informed consent in a vaccine field trial in a developing country setting 
BMC Medical Ethics  2008;9:15.
Informed consent is an ethical and legal requirement for research involving human participants. However, few studies have evaluated the process, particularly in Africa.
Participants in a case control study designed to identify correlates of immune protection against tuberculosis (TB) in South Africa. This study was in turn nested in a large TB vaccine efficacy trial.
The aim of the study was to evaluate the quality of consent in the case control study, and to identify factors that may influence the quality of consent.
Cross-sectional study conducted over a 4 month period.
Consent was obtained from parents of trial participants. These parents were asked to complete a questionnaire that contained questions about the key elements of informed consent (voluntary participation, confidentiality, the main risks and benefits, etc.). The recall (success in selecting the correct answers) and understanding (correctness of interpretation of statements presented) were measured.
The majority of the 192 subjects interviewed obtained scores greater than 75% for both the recall and understanding sections. The median score for recall was 66%; interquartile range (IQR) = 55%–77% and for understanding 75% (IQR = 50%–87%). Most (79%) were aware of the risks and 64% knew that they participated voluntarily. Participants who had completed Grade 7 at school and higher were more likely (OR = 4.94; 95% CI = 1.57 – 15.55) to obtain scores greater than 75% for recall than those who did not. Participants who were consented by professional nurses who had worked for more than two years in research were also more likely (OR = 2.62; 95% CI = 1.35–5.07) to obtain such scores for recall than those who were not.
Notwithstanding the constraints in a developing country, in a population with low levels of literacy and education, the quality of informed consent found in this study could be considered as building blocks for establishing acceptable standards for public health research. Education level of respondents and experience of research staff taking the consent were associated with good quality informed consent.
PMCID: PMC2575196  PMID: 18826637
18.  A Randomized Controlled Trial of Short and Standard-Length Consent Forms for a Genetic Cohort Study: Is Longer Better? 
Journal of Epidemiology  2012;22(4):308-316.
Although the amount of detail in informed consent documents has increased over time and the documents have therefore become very long, there is little research on whether longer informed consent documents actually result in (1) better informed research subjects or (2) higher consent rates. We therefore conducted an add-on randomized controlled trial to the Takashima Study, a prospective Japanese population-based genetic cohort study, to test the hypothesis that a shorter informed consent form would satisfy both of the above goals.
Standard (10 459 words, 11 pages) and short (3602 words, 5 pages) consent forms in Japanese were developed and distributed using cluster-randomization to 293 potential cohort subjects living in 9 medico-social units and 288 subjects in 8 medico-social units, respectively.
Few differences were found between the 2 groups with regard to outcome measures, including participants’ self-perceived understanding, recall of information, concerns, voluntariness, trust, satisfaction, sense of duty, and consent rates.
A short informed consent form was no less valid than a standard form with regard to fulfilling ethical requirements and securing the scientific validity of research.
PMCID: PMC3798649  PMID: 22447213
informed consent; cohort study; ethics; genetics; randomization
19.  Cancer patient perceptions on the ethical and legal issues related to biobanking 
Understanding the perception of patients on research ethics issues related to biobanking is important to enrich ethical discourse and help inform policy.
We examined the views of leukemia patients undergoing treatment in clinics located in the Princess Margaret Hospital in Toronto, Ontario, Canada. An initial written survey was provided to 100 patients (64.1% response rate) followed by a follow-up survey (62.5% response rate) covering the topics of informed consent, withdrawal, anonymity, incidental findings and the return of results, ownership, and trust.
The majority (59.6%) preferred one-time consent, 30.3% desired a tiered consent approach that provides multiple options, and 10.1% preferred re-consent for future research. When asked different questions on re-consent, most (58%) reported that re-consent was a waste of time and money, but 51.7% indicated they would feel respected and involved if asked to re-consent. The majority of patients (62.2%) stated they had a right to withdraw their consent, but many changed their mind in the follow-up survey explaining that they should not have the right to withdraw consent. Nearly all of the patients (98%) desired being informed of incidental health findings and explained that the information was useful. Of these, 67.3% of patients preferred that researchers inform them and their doctors of the results. The majority of patients (62.2%) stated that the research institution owns the samples whereas 19.4% stated that the participants owned their samples. Patients had a great deal of trust in doctors, hospitals and government-funded university researchers, moderate levels of trust for provincial governments and industry-funded university researchers, and low levels of trust towards industry and insurance companies.
Many cancer patients surveyed preferred a one-time consent although others desired some form of control. The majority of participants wanted a continuing right to withdraw consent and nearly all wanted to be informed of incidental findings related to their health. Patients had a great deal of trust in their medical professionals and publically-funded researchers as opposed to profit-based industries and insurance companies.
PMCID: PMC3599691  PMID: 23497701
Biobank; Tissue repository; Cancer patient perspectives; Consent; Withdrawal; Anonymity; Incidental findings; Return of results; Ownership; Trust
20.  Associations between Mode of HIV Testing and Consent, Confidentiality, and Referral: A Comparative Analysis in Four African Countries 
PLoS Medicine  2012;9(10):e1001329.
A study carried out by Carla Obermeyer and colleagues examines whether practices regarding consent, confidentiality, and referral vary depending on whether HIV testing is provided through voluntary counseling and testing or provider-initiated testing.
Recommendations about scaling up HIV testing and counseling highlight the need to provide key services and to protect clients' rights, but it is unclear to what extent different modes of testing differ in this respect. This paper examines whether practices regarding consent, confidentiality, and referral vary depending on whether testing is provided through voluntary counseling and testing (VCT) or provider-initiated testing.
Methods and Findings
The MATCH (Multi-Country African Testing and Counseling for HIV) study was carried out in Burkina Faso, Kenya, Malawi, and Uganda. Surveys were conducted at selected facilities. We defined eight outcome measures related to pre- and post-test counseling, consent, confidentiality, satisfactory interactions with providers, and (for HIV-positive respondents) referral for care. These were compared across three types of facilities: integrated facilities, where testing is provided along with medical care; stand-alone VCT facilities; and prevention of mother-to-child transmission (PMTCT) facilities, where testing is part of PMTCT services. Tests of bivariate associations and modified Poisson regression were used to assess significance and estimate the unadjusted and adjusted associations between modes of testing and outcome measures. In total, 2,116 respondents tested in 2007 or later reported on their testing experience. High percentages of clients across countries and modes of testing reported receiving recommended services and being satisfied. In the unadjusted analyses, integrated testers were less likely to meet with a counselor before testing (83% compared with 95% of VCT testers; p<0.001), but those who had a pre-test meeting were more likely to have completed consent procedures (89% compared with 83% among VCT testers; p<0.001) and pre-test counseling (78% compared with 73% among VCT testers; p = 0.015). Both integrated and PMTCT testers were more likely to receive complete post-test counseling than were VCT testers (59% among both PMTCT and integrated testers compared with 36% among VCT testers; p<0.001). Adjusted analyses by country show few significant differences by mode of testing: only lower satisfaction among integrated testers in Burkina Faso and Uganda, and lower frequency of referral among PMTCT testers in Malawi. Adjusted analyses of pooled data across countries show a higher likelihood of pre-test meeting for those testing at VCT facilities (adjusted prevalence ratio: 1.22, 95% CI: 1.07–1.38) and higher satisfaction for stand-alone VCT facilities (adjusted prevalence ratio: 1.15; 95% CI: 1.06–1.25), compared to integrated testing, but no other associations were statistically significant.
Overall, in this study most respondents reported favorable outcomes for consent, confidentiality, and referral. Provider-initiated ways of delivering testing and counseling do not appear to be associated with less favorable outcomes for clients than traditional, client-initiated VCT, suggesting that testing can be scaled up through multiple modes without detriment to clients' rights.
Please see later in the article for the Editors' Summary
Editors' Summary
In 2007, World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) issued a joint guidance document on “provider-initiated” HIV testing and counseling. They noted that previous testing strategies that relied on “client-initiated” testing (also referred to as VCT, for voluntary counseling and testing) had failed to reach enough people, both in high-income and resource-constrained countries—in Africa, for example, at that time, just 12% of men and 10% of women had ever been tested. They argued that many opportunities to diagnose and counsel people that visit health facilities for other reasons are being missed, and that provider-initiated HIV testing and counseling can help expand access to HIV treatment, care, and support. They made it clear, however, that mandatory testing is not acceptable. All provider-initiated testing must therefore give individuals the option to not be tested. In addition, the guidelines stressed that all testing must continue to observe “the three Cs” (informed consent, counseling, and confidentiality) and be accompanied by an “enabling environment” including the availability of antiretroviral therapy, prevention and support services, and a supportive social, policy, and legal framework. A number of advocates have subsequently criticized the guidelines for failing to recognize that health-care services and staff in some countries do not always observe the three Cs. Critics have also questioned the appropriateness of the strategy for settings where antiretroviral therapy is not always available or where stigma and discrimination remain widespread.
Why Was This Study Done?
To inform the debate surrounding scale-up of HIV testing in general and provider-initiated testing in particular with data on “real-life” testing, researchers have since carried out a number of studies. One of them, called MATCH (for Multi-Country African Testing and Counseling for HIV), was designed to allow systematic comparisons across African countries of different ways of HIV testing. Its goal was to investigate the uptake of testing, to analyze differences in the experience of testing across countries and modes of testing, and to use the results to devise better strategies to increase knowledge of HIV status and referral to care. MATCH used different means to collect information, including surveys and interviews. People from Burkina Faso, Kenya, Malawi, and Uganda participated. Some had undergone HIV testing, others had not. This study used a subset of the survey data collected for the MATCH study and asked whether there were systematic differences depending on the type of testing people had experienced.
What Did the Researchers Do and Find?
The data the researchers used were from 2,116 people who had undergone testing in the two previous years at different facilities in the four countries. The different facilities were grouped into three “modes” of testing: VCT-only testing, integrated testing (which included hospitals and other medical facilities where provider-initiated and client-initiated testing were both available, along with other medical services), and prevention of mother-to-child transmission (PMTCT) testing at medical facilities offering services to pregnant women. Analyzing the survey responses, the researchers categorized them as related to eight different “outcomes”: pre-test meeting, pre-test counseling, consent, confidentiality, satisfaction with the person-to-person interactions, post-test meeting to receive results, post-test counseling, and referral to care.
They found that across countries and different facilities, the majority of participants reported having received most of the testing-related services. More than 90% reported having a pre-test meeting, and around 80% were satisfied with the personal interactions, with the consent process, and with confidentiality. About 50% of participants reported receiving all post-test services, and 71% of those who had tested positive for HIV reported appropriate referral to care.
When they looked for differences between different modes of testing, the researchers found that while they existed, they did not consistently favor one mode over another. Some outcomes scored higher in VCT facilities, some in PMTCT facilities, and some in integrated facilities.
What Do These Findings Mean?
While there is room for improvement in HIV testing services (especially post-test services) across the countries and facilities included, the study did not reveal major problems with consent or confidentiality. The results also suggest that services at PMTCT and integrated facilities are not any worse than those at VCT-only sites. It seems therefore reasonable to continue expanding access to HIV testing and to include all facilities in the scale-up. That said, this is only one of a number of studies examining issues surrounding HIV testing, and decisions should be based on all available evidence. The results here are consistent with some of the other studies, but there are also reports that counseling might become neglected as testing is scaled up, and that offering testing routinely at every doctor's visit makes it seem mandatory even if there is the possibility to “opt out.” Other analyses of the MATCH study use in-depth interviews to understand in more detail the feelings, experiences, and attitudes of participants who have been tested as well as those who have not been tested. It will be important to see whether their results are consistent with the ones here, which are based on a survey of people who have been tested.
Additional Information
Please access these websites via the online version of this summary at
WHO has published a toolkit for scaling up HIV testing and counseling services in resource-limited settings, as well as the report Service Delivery Approaches to HIV Testing and Counselling (HSC): A Strategic HTC Programme Framework
In response to reactions to the 2007 joint WHO/UNAIDS guidelines Guidance on Provider-Initiated HIV Testing and Counselling in Health Facilities, the UNAIDS Reference Group on HIV and Human Rights issued a Statement and Recommendations on Scaling up HIV Testing and Counselling
The NAM/aidsmap website has a section on HIV testing policies and guidelines.
PMCID: PMC3479110  PMID: 23109914
21.  Surrogate consent for dementia research 
Neurology  2009;72(2):149-155.
Research in novel therapies for Alzheimer disease (AD) relies on persons with AD as research subjects. Because AD impairs decisional capacity, informed consent often must come from surrogates, usually close family members. But policies for surrogate consent for research remain unsettled after decades of debate.
We designed a survey module for a random subsample (n = 1,515) of the 2006 wave of the Health and Retirement Study, a biennial survey of a nationally representative sample of Americans aged 51 and older. The participants answered questions regarding one of four randomly assigned surrogate-based research (SBR) scenarios: lumbar puncture study, drug randomized control study, vaccine study, and gene transfer study. Each participant answered three questions: whether our society should allow family surrogate consent, whether one would want to participate in the research, and whether one would allow one’s surrogate some or complete leeway to override stated personal preferences.
Most respondents stated that our society should allow family surrogate consent for SBR (67.5% to 82.5%, depending on the scenario) and would themselves want to participate in SBR (57.4% to 79.7%). Most would also grant some or complete leeway to their surrogates (54.8% to 66.8%), but this was true mainly of those willing to participate. There was a trend toward lower willingness to participate in SBR among those from ethnic or racial minority groups.
Family surrogate consent–based dementia research is broadly supported by older Americans. Willingness to allow leeway to future surrogates needs to be studied further for its ethical significance for surrogate-based research policy.
= Alzheimer disease;
= confidence interval;
= Health and Retirement Study;
= legally authorized representatives;
= lumbar puncture;
= odds ratio;
= randomized controlled trial;
= surrogate-based research.
PMCID: PMC2663398  PMID: 19139366
22.  Managing clinical research permissions electronically 
Clinical trials (London, England)  2013;10(4):604-611.
One mechanism to increase participation in research is to solicit potential research participants’ general willingness to be recruited into clinical trials. Such research permissions and consents typically are collected on paper upon patient registration. We describe a novel method of capturing this information electronically.
The objective is to enable the collection of research permissions and informed consent data electronically to permit tracking of potential research participants’ interest in current and future research involvement and to provide a foundation for facilitating the research workflow.
The project involved systematic analysis focused on key areas, including existing business practices, registration processes, and permission collection workflows, and ascertaining best practices for presenting consent information to users via tablet technology and capturing permissions data. Analysis was followed by an iterative software development cycle with feedback from subject matter experts and users.
An initial version of the software was piloted at one institution in South Carolina for a period of 1 year, during which consents and permission were collected during 2524 registrations of patients. The captured research permission data were transmitted to a clinical data warehouse. The software was later released as an open-source package that can be adopted for use by other institutions.
There are significant ethical, legal, and informatics challenges that must be addressed at an institution to deploy such a system. We have not yet assessed the long-term impact of the system on recruitment of patients to clinical trials.
We propose that by improving the ability to track willing potential research participants, we can improve recruitment into clinical trials and, in the process, improve patient education by introducing multimedia to informed consent documents.
PMCID: PMC4213063  PMID: 23785065
23.  Emerging issues in paediatric health research consent forms in Canada: working towards best practices 
BMC Medical Ethics  2013;14:5.
Obtaining a research participant’s voluntary and informed consent is the bedrock of sound ethics practice. Greater inclusion of children in research has led to questions about how paediatric consent operates in practice to accord with current and emerging legal and socio-ethical issues, norms, and requirements.
Employing a qualitative thematic content analysis, we examined paediatric consent forms from major academic centres and public organisations across Canada dated from 2008–2011, which were purposively selected to reflect different types of research ethics boards, participants, and studies. The studies included biobanking, longitudinal studies, and gene-environment studies. Our purpose was to explore the following six emerging issues: (1) whether the scope of parental consent allows for a child’s assent, dissent, or future consent; (2) whether the concepts of risk and benefit incorporate the child’s psychological and social perspective; (3) whether a child’s ability to withdraw is respected and to what extent withdrawal is permitted; (4) whether the return of research results includes individual results and/or incidental findings and the processes involved therein; (5) whether privacy and confidentiality concerns adequately address the child’s perspective and whether standard data and/or sample identifiability nomenclature is used; and (6) whether retention of and access to paediatric biological samples and associated medical data are addressed.
The review suggests gaps and variability in the consent forms with respect to addressing each of the six issues. Many forms did not discuss the possibility of returning research results, be they individual or general/aggregate results. Forms were also divided in terms of the scope of parental consent (specific versus broad), and none discussed a process for resolving disputes that can arise when either the parents or the child wishes to withdraw from the study.
The analysis provides valuable insight and evidence into how consent forms address current ethical issues. While we do not thoroughly explore the contexts and reasons behind consent form gaps and variability, we do advocate and formulate the development of best practices for drafting paediatric health research consent forms. This can greatly ameliorate current gaps and facilitate harmonised and yet contextualised approaches to paediatric health research ethics.
PMCID: PMC3571865  PMID: 23363554
Children; Confidentiality; Consent; ELSI; Paediatric research; Research ethics; Return of results; Withdrawal
24.  A Rural Community's Involvement in the Design and Usability Testing of a Computer-Based Informed Consent Process for the Personalized Medicine Research Project 
Many informed consent studies demonstrate that research subjects poorly retain and understand information in written consent documents. Previous research in multimedia consent is mixed in terms of success for improving participants’ understanding, satisfaction, and retention. This failure may be due to a lack of a community-centered design approach to building the interventions. The goal of this study was to gather information from the community to determine the best way to undertake the consent process. Community perceptions regarding different computer-based consenting approaches were evaluated, and a computer-based consent was developed and tested. A second goal was to evaluate whether participants make truly informed decisions to participate in research. Simulations of an informed consent process were videotaped to document the process. Focus groups were conducted to determine community attitudes towards a computer-based informed consent process. Hybrid focus groups were conducted to determine the most acceptable hardware device. Usability testing was conducted on a computer-based consent prototype using a touch-screen kiosk. Based on feedback, a computer-based consent was developed. Representative study participants were able to easily complete the consent, and all were able to correctly answer the comprehension check questions. Community involvement in developing a computer-based consent proved valuable for a population-based genetic study. These findings may translate to other types of informed consents, such as genetic clinical trials consents. A computer-based consent may serve to better communicate consistent, clear, accurate, and complete information regarding the risks and benefits of study participation. Additional analysis is necessary to measure the level of comprehension of the check-question answers by larger numbers of participants. The next step will involve contacting participants to measure whether understanding of what they consented to is retained over time.
PMCID: PMC4145717  PMID: 24273095
Decision making; focus groups; genetic research; computer-based informed consent; usability
25.  Preservation of the Capacity to Appoint a Proxy Decision Maker: Implications for Dementia Research 
Archives of General Psychiatry  2011;68(2):214-220.
Research involving persons with impaired decision-making capacity, such as persons with Alzheimer’s disease, remains ethically challenging, especially when the research involves significant risk. If subjects incapable of consenting to research studies were still able to appoint a research proxy, it would allow for an appointed surrogate, rather than a de facto surrogate, to represent the subject.
To assess the extent to which persons with Alzheimer’s disease retain their capacity to appoint a research proxy.
Design, Setting, and Participants
188 persons with Alzheimer’s disease were interviewed for their capacity to appoint a proxy (CAP) for research and to provide consent to two hypothetical research scenarios, a lower risk randomized clinical trial testing a new drug (drug RCT) and a higher risk randomized clinical trial testing neurosurgical cell implants using a sham control condition (neurosurgical RCT). Categorical capacity status for each subject was determined by independent videotape reviews of capacity interviews by five experienced psychiatrists.
Main Outcome Measures
Categorical capacity determinations for the capacity to appoint a research proxy, capacity to consent to a drug RCT, and capacity to consent to a neurosurgical RCT.
37.7% (40/106) of those deemed incapable of consenting to the drug RCT and 54.4% (86/157) of those deemed incapable of consenting to the neurosurgical RCT were still found capable of appointing a research proxy. Very few subjects (7/186, 3.8%) were deemed capable of consenting to the neurosurgical RCT by all five psychiatrists.
A substantial proportion of AD subjects thought incapable of consenting to lower or to higher risk studies have preserved capacity for appointing a research proxy. Since so few subjects are found to be unequivocally capable of providing independent consent to higher risk AD research, providing for an appointed surrogate even after the onset of AD, which might best be done in the very early stages of the illness, may help address key ethical challenges to AD research.
PMCID: PMC3349937  PMID: 21300949

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