WHAT SHOULD RESEARCH PARTICIPANTS UNDERSTAND TO UNDERSTAND THEY ARE PARTICIPANTS IN RESEARCH?

To give valid informed consent to participate in clinical research, potential participants should understand the risks, potential benefits, procedures, and alternatives. Potential participants also should understand that they are being invited to participate in research. Yet it is unclear what potential participants need to understand to satisfy this particular requirement. As a result, it is unclear what additional information investigators should disclose about the research; and it is also unclear when failures of understanding in this respect undermine the validity of potential participants' informed consent. An analysis of individuals' interests suggests that potential participants need to understand three additional facts to understand that they are being invited to participate in research: 1) research contribution : those who enroll in the study will be contributing to a project designed to gather generalizable knowledge to benefit others in the future; 2) research relationship : the investigators will rely on participants' efforts to gather the generalizable knowledge to benefit others; and 3) research impact : the extent to which participating in the study will alter what participants do and what happens to them.     

A Randomised Controlled Trial of Consent Procedures for the Use of Residual Tissues for Medical Research: Preferences of and Implications for Patients,Research and Clinical Practice

Background

Despite much debate, there is little evidence on consequences of consent procedures for residual tissue use. Here, we investigated these consequences for the availability of residual tissue for medical research, clinical practice, and patient informedness.

Methods

We conducted a randomised clinical trial with three arms in six hospitals. Participants, patients from whom tissue had been removed for diagnosis or treatment, were randomised to one of three arms: informed consent, an opt-out procedure with active information provision (opt-out plus), and an opt-out procedure without active information provision. Participants received a questionnaire six weeks post-intervention; a subsample of respondents was interviewed. Health care providers completed a pre- and post-intervention questionnaire. We assessed percentage of residual tissue samples available for medical research, and patient and health care provider satisfaction and preference. Health care providers and outcome assessors could not be blinded.

Results

We randomised 1,319 patients, 440 in the informed consent, 434 in the opt-out plus, and 445 in the opt-out arm; respectively 60.7%, 100%, and 99.8% of patients’ tissue samples could be used for medical research. Of the questionnaire respondents (N = 224, 207, and 214 in the informed consent, opt-out plus, and opt-out arms), 71%, 69%, and 31%, respectively, indicated being (very) well informed. By questionnaire, the majority (53%) indicated a preference for informed consent, whereas by interview, most indicated a preference for opt-out plus (37%). Health care providers (N = 35) were more likely to be (very) satisfied with opt-out plus than with informed consent (p = 0.002) or opt-out (p = 0.039); the majority (66%) preferred opt-out plus.

Conclusion

We conclude that opt-out with information (opt-out plus) is the best choice to balance the consequences for medical research, patients, and clinical practice, and is therefore the most optimal consent procedure for residual tissue use in Dutch hospitals.

Trial Registration

Dutch Trial Register NTR2982     

Best Practice Guidelines on Informed Consent for Weight Loss Surgery Patients

Objective: To provide evidence‐based guidelines on informed consent and the education that underlies it for legally competent, severely obese weight loss surgery (WLS) patients. Research Methods and Procedures: We conducted a systematic review of the scientific literature published on MEDLINE between 1984 and 2004. Three articles focused on informed consent for WLS; none was based on empirical studies. We summarized each paper and assigned evidence categories according to a grading system derived from established evidence‐based models. We also relied on informed consent and educational materials from six WLS programs in Massachusetts. All evidence is Category D. Recommendations were based on a review of the available literature, informed consent materials from WLS programs, and expert opinion. Results: This Task Group found that the informed consent process contributes to long‐term outcome in multiple ways but is governed by limited legal requirements. We focused our report on the legal and ethical issues related to informed consent, i.e., disclosure vs. comprehension. Recommendations centered on the importance of assessing patient comprehension of informed consent materials, the content of those materials, and the use of active teaching/learning techniques to promote understanding. Discussion: Although demonstrated comprehension is not a legal requirement for informed consent in Massachusetts or other states, the members of this Task Group found that the best interests of WLS patients, providers, and facilities are served when clinicians engage patients in active learning and collaborative decision making.     

Evaluation of the content and process of informed consent discussions for neonatal research

studies of informed consent for neonatal research suggest that there are gaps in parental understanding of key aspects of research. Few studies have examined parental understanding and investigator disclosure simultaneously. This pilot study evaluated the content and processes of 21 audio-recorded consent discussions with parents of eligible newborns, as well as parents' self-reported comprehension of research elements following these discussions. Gaps in both investigator disclosure and parental understanding were found. Nevertheless, parents reported comprehension of a greater number of research elements than were actually disclosed by investigators. Our preliminary results indicate the feasibility and potential utility of jointly examining parental understanding and investigator behavior to characterize consent for neonatal research. Directions for future research are suggested.     

Informed consent and collaborative research: perspectives from the developing world

Introduction: Informed consent has been recognized as an important component of research protocols and procedures of disclosure and consent in collaborative research have been criticized, as they may not be in keeping with cultural norms of developing countries. This study, which is part of a larger project funded by the United States National Bioethics Advisory Commission, explores the opinions of developing country researchers regarding informed consent in collaborative research. Methods: A survey of developing country researchers, involved in human subject research, was conducted by distributing a questionnaire with 169 questions, which included questions relating to informed consent. In addition, six focus group discussions, eight in-depth interviews and 78 responses to open-ended questions in the questionnaire provided qualitative data. Results: 203 surveys were considered complete and were included in the analysis. Written consent was not used by nearly 40% of the researchers in their most recent studies. A large proportion of respondents recommended that human subject regulations should allow more flexibility in ways of documenting informed consent. 84% of researchers agreed that a mechanism to measure understanding should be incorporated in research studies as part of the process of informed consent. Discussion: This paper is an empirical step in highlighting the ethical issues concerning disclosure. Health researchers in developing countries are well aware of the importance of consent in health research, and equally value the significance of educating human subjects regarding study protocols and associated risks and benefits. However, respondents emphasize the need for modifying ethical regulations in collaborative research.     

Patients' Perception of Quality of Pre-Operative Informed Consent in Athens,Greece: A Pilot Study

Background

We sought to perform a study to record and evaluate patients'' views of the way surgeons communicate informed consent (IC) in Greece.

Methodology/Principal Findings

A prospective pilot study was carried out in Athens from 9/2007 to 4/2008. The study sample was extracted from patients, operated by eight different surgeons, who volunteered to fill in a post-surgery self-report questionnaire on IC. A composite delivered information index and a patient-physician relationship index were constructed for the purposes of the analysis. In total, 77 patients (42 males) volunteered to respond to the questionnaire. The delivered information index scores ranged from 3 to 10, the mean score was 8, and the standard deviation (SD) was 1.9. All patients were aware of their underlying diagnosis and reason for surgery. However, a considerable proportion of the respondents (14.3%) achieved a score below or equal to 5. The patient-physician relationship scores ranged from 0 to 20, the mean score was 16 and the standard deviation (SD) was 4.3. The better the patient-physician relationship, the more information was finally delivered to the patient from the physician (Spearman''s rank-order correlation coefficient was 0.4 and p<0.001). Delivered information index was significantly higher among participants who comprehended the right to informed consent, compared to participants who did not (p<0.001), and among participants who were given information regarding other possible therapeutic options (p = 0.001). 43% of the respondents answered that less than 10 minutes were spent on the consent process, 58.4% of patients stated that they had not been informed about other possible therapeutic choices and 28.6% did not really comprehend their legal rights to IC.

Conclusions

Despite the inherent limitations and the small sample size that do not permit to draw any firm conclusions, results indicate that a successful IC process may be associated with specific elements such as the patient-physician relationship, the time spent by the physician to inform the patient, a participant''s comprehension of the right to IC and the provision of information regarding other possible therapeutic options.     

Parents’ Education Shapes,but Does Not Originate,the Disability Representations of Their Children

The present research tested whether children’s disability representations are influenced by cultural variables (e.g., social activities, parent education, custom complex variables) or by cognitive constraints. Four questionnaires were administered to a sample of 76 primary school aged children and one of their parents (n = 152). Questionnaires included both open-ended and closed-ended questions. The open-ended questions were created to collect uncensored personal explanations of disability, whereas the closed-ended questions were designed to elicit a response of agreement for statements built on the basis of the three most widespread disability models: individual, social, and biopsychosocial. For youngest children (6–8 years old), people with disabilities are thought of as being sick. This early disability representation of children is consistent with the individual model of disability and independent from parents’ disability explanations and representations. As children grow older (9–11 years old), knowledge regarding disability increases and stereotypical beliefs about disability decrease, by tending to espouse their parents representations. The individual model remains in the background for the adults too, emerging when the respondents rely on their most immediately available mental representation of disability such as when they respond to an open-ended question. These findings support that the youngest children are not completely permeable to social representations of disability likely due to cognitive constraints. Nevertheless, as the age grows, children appear educable on perspectives of disability adhering to a model of disability representation integral with social context and parent perspective.     

Informed consent for controlled human infection studies in low- and middle-income countries: Ethical challenges and proposed solutions

In controlled human infection studies (CHIs), participants are deliberately exposed to infectious agents in order to better understand the mechanism of infection or disease and test therapies or vaccines. While most CHIs have been conducted in high-income countries, CHIs have recently been expanding into low- and middle-income countries (LMICs). One potential ethical concern about this expansion is the challenge of obtaining the voluntary informed consent of participants, especially those who may not be literate or have limited education. In some CHIs in LMICs, researchers have attempted to address this potential concern by limiting access to literate or educated populations. In this paper, we argue that this practice is unjustified, as it does not increase the chances of obtaining valid informed consent and therefore unfairly excludes illiterate populations and populations with lower education. Instead, we recommend that investigators improve the informed consent process by drawing on existing data on obtaining informed consent in these populations and interventions aimed at improving their understanding. Based on a literature review, we provide concrete suggestions for how to follow this recommendation and ensure that populations with lower literacy or education are given a fair opportunity to protect their rights and interests in the informed consent process.     

Understanding informed consent for participation in international health research

To participate in health research, there is a need for well-administered informed consent. Understanding of informed consent, especially in international health research, is influenced by the participants' understanding of information and the meaning attached to the information communicated to them regarding the purpose and procedure of the research. Incorrect information and the power differential between researcher and participants may lead to participants becoming victims of harmful research procedures. Meningitis epidemics in Kano in early 1996 led to a response from drug companies, especially Pfizer, as well as humanitarian workers from Médecins Sans Frontiers, which resulted in an unethical trial. Pfizer's drug trial during the epidemics has left a lasting controversy, which has yet to be resolved. This paper examines the key issues surrounding the controversy, discusses the context of informed decision-making, the ethical issues and implications of the incident, and concludes with some recommendations. Relevant texts, journals, Internet materials, newspaper articles and documentary materials on the conduct of the Pfizer's Trovan trial have been consulted. Four types of action (act intuitively, act rationally, act ignorantly, and act contextually – based on information provided) are identified as possible options for decision making. Participants most likely acted in ignorance due to poor understanding of the information contained in the verbal informed consent administered, thereby raising ethical issues. It is concluded that health research ethics committees have an important role to play nationally and locally in overseeing research, and in avoiding future occurrences.     

Medical experimentation, informed consent and using people

In this paper we argue that the standard focus on problems of informed consent in debates about the ethics of human experimentation is inadequate because it fails to capture a more fundamental way in which such experiments may be wrong. Taking clinical trials as our case in point, we suggest that it is the moral offence of using people as mere means which better characterizes what is wrong with violations of personal autonomy in certain kinds of clinical trials. This account also helps bring out another important way in which the autonomy of the participants in clinical trials my be violated, even in cases where they have given informed consent to their involvement. Where relevant information about the trial is framed in such a way as to induce a patient's participation by appeal to their nonrational preferences, this is also a violation of their autonomy, and one which is distinct from a failure of informed consent. The underlying wrongness of both kinds of violations, we argue, is plausibly captured by the moral offence of using people as mere means.     

Consent for participating in clinical trials ‐ Is it really informed?

The article explores the challenges of ensuring voluntary and informed consent which is obtained from potential research subjects in the north‐eastern part of Romania. This study is one of the first empirical papers of this nature in Romania. The study used a quantitative survey design using the adapted Quality of Informed Consent (QuIC) questionnaire. The target population consisted of 100 adult persons who voluntarily enrolled in clinical trials. The informed consent form must contain details regarding the potential risks and benefits, the aim of the clinical trial, study design, confidentiality, insurance and contact details in case of additional questions. Our study confirmed that although all required information was included in the ICF, few clinical trial participants truly understood it. We also found that the most important predictive factor for a good subjective and objective understanding of the clinical trial was the level of education. Our study suggests that researchers should consider putting more effort in order to help clinical trials participants achieve a better understanding of the informed consent. In this way they will ensure that participants’ decision‐making is meaningful and that their interests are protected.     

Consent and confidentiality in the light of recent demands for data sharing

Many attempts have been made to formalize ethical requirements for research. Among the most prominent mechanisms are informed consent requirements and data protection regimes. These mechanisms, however, sometimes appear as obstacles to research. In this opinion paper, we critically discuss conventional approaches to research ethics that emphasize consent and data protection. Several recent debates have highlighted other important ethical issues and underlined the need for greater openness in order to uphold the integrity of health‐related research. Some of these measures, such as the sharing of individual‐level data, pose problems for standard understandings of consent and privacy. Here, we argue that these interpretations tend to be overdemanding: They do not really protect research subjects and they hinder the research process. Accordingly, we suggest another way of framing these requirements. Individual consent must be situated alongside the wider distribution of knowledge created when the actions, commitments, and procedures of researchers and their institutions are opened to scrutiny. And instead of simply emphasizing privacy or data protection, we should understand confidentiality as a principle that facilitates the sharing of information while upholding important safeguards. Consent and confidentiality belong to a broader set of safeguards and procedures to uphold the integrity of the research process.     

Best Practice Updates for Informed Consent and Patient Education in Weight Loss Surgery

To update evidence‐based best practice guidelines for obtaining informed consent from weight loss surgery (WLS) patients, with an emphasis on appropriate content and communications approaches that might enhance patient understanding of the information, we performed a systematic search of English‐language literature published between April 2004 and May 2007 in MEDLINE and the Cochrane database. Keywords included WLS and informed consent, comprehension, health literacy, and patient education; and WLS and outcomes, risk, patient safety management, and effectiveness. Recommendations are based on the most current literature and the consensus of the expert panel; they were graded according to systems used in established evidence‐based models. We identified over 120 titles, 38 of which were reviewed in detail. Evidence suggests that WLS outcomes, including long‐term rates of relapse, vary by procedure. For some weight loss surgeries, long‐term outcomes may not be known. Risks also vary by patient and provider characteristics. Informed consent should incorporate realistic projections of the short‐ and long‐term risks, benefits, and consequences of surgery, as well as alternatives to WLS. For consent to be informed, the education process should continue until the patient demonstrates comprehension of all relevant material and concepts. Confirmation of comprehension can protect patients engaged in the process of consent for WLS. Future research should focus on the outcomes and consequences of WLS, and different approaches that facilitate patient understanding of, and decision making about, WLS.     

Trends in health research ethics in the Philippines during the American Colonial Period (1898‐1946)

Research involving human participants has been conducted in the Philippines since the beginning of the Spanish colonial period. Such studies are expected to adhere to internationally accepted ethical guidelines. This paper discusses trends in clinical research ethics in the Philippines during the American colonial period (1898‐1946). Specifically, studies were assessed on: 1) their observance of ethical protocols, including review; 2) identification of inclusion and exclusion criteria in the selection of participants; 3) use of vulnerable subjects; and 4) practice of the informed consent process. Only the informed consent process had a significant logistic correlation with progression of years. Recruitment of vulnerable groups was common during this period; children and prisoners were the most common participants. Trends in medical ethics in the Philippines reflected those in the United States prior to the publication of the Nuremberg Code, which served as a milestone in the protection of human welfare in clinical research.     

Citizens’ understanding of welfare of animals on the farm: An empirical study

Many people believe that welfare standards for nonhuman animals on farms need to be improved. However, the definition of farm animal welfare (FAW) remains unclear, as different disciplines have developed competing understandings of FAW. Some studies have investigated citizens’ understanding of FAW through quantitative surveys. This study combined both closed-ended and open-ended questions and compared the findings from the different types of questions. For the open-ended question, respondents mostly named criteria in the categories of “housing system” and “management practice”; however, for the closed-ended question, the category “animal health” was most important. These findings suggest that not only whom you ask determines what comprises animal welfare, but how you ask. These findings should be considered when developing new animal welfare programs to increase the likelihood that the new programs will be accepted by the broader public and meet its expectations. In particular, improvements concerning animal health need to be publicized and clearly communicated to citizens, as health-related aspects are important to many people even though those aspects may not be the first thing they mentioned when asked.     

To What did They Consent? Understanding Consent Among Low Literacy Participants in a Microbicide Feasibility Study in Mazabuka,Zambia

We conducted a study to review the consenting process in a vaginal Microbicide feasibility study conducted in Mazabuka, Zambia. Participants were drawn from those participating in the microbicide study. A questionnaire and focus group discussion were used to collect information on participants understanding of study aims, risks and benefits. Altogether, 200 participants took part in this study. The results of the study showed that while all participants signed or endorsed their thumbprints to the consent forms, full informed consent was not attained from most of the participants since 77% (n = 154) of the participants had numerous questions about the study and 34% (n = 68) did not know who to get in touch with concerning the study. Study objectives were not fully understood by over 61% of the participants. Sixty four percent of the participants were not sure of the risks of taking part in the microbicide study. A significant number thought the study was all about determining their HIV status. Some participants were concerned that their partners were not on the trial as they were convinced that being on the study meant that that they had a lifetime protection from HIV infection. The process of obtaining consent was inadequate as various phases of the study were not fully understood. We recommend the need for researchers to reinforce the consenting process in all studies and more so when studies are conducted in low literacy populations.     

Perceived challenges in the informed consent process: Mismatches between enrollers and researchers at a South African clinical research site

Enrollers play a critical yet often overlooked role in clinical research, particularly in informed consent processes. Study retention may depend in part on how complex information is conveyed to potential participants. This qualitative study aimed to assess communicative barriers during consent and enrolment in two South African TB/HIV clinical studies. In particular, we compared our own perceptions of potential challenges to consent with that of thirteen enrollers, gained via reflective journaling and focus group discussions. Some overlap of identified challenges was evident, including terminology, jargon and consent document format. However there were mismatches to identified challenges. Enrollers provided further insights into potential challenges to consent, in particular, blood withdrawal, discussion of sexual issues and misunderstanding of study participation. Enrollers also reported feeling ill‐equipped to provide counselling when participants became distressed. We offer several recommendations for strengthening the inclusion of enrollers in the development of clinical research protocols and consent documents.     

Proprioceptive Interaction between the Two Arms in a Single-Arm Pointing Task

Proprioceptive signals coming from both arms are used to determine the perceived position of one arm in a two-arm matching task. Here, we examined whether the perceived position of one arm is affected by proprioceptive signals from the other arm in a one-arm pointing task in which participants specified the perceived position of an unseen reference arm with an indicator paddle. Both arms were hidden from the participant’s view throughout the study. In Experiment 1, with both arms placed in front of the body, the participants received 70–80 Hz vibration to the elbow flexors of the reference arm (= right arm) to induce the illusion of elbow extension. This extension illusion was compared with that when the left arm elbow flexors were vibrated or not. The degree of the vibration-induced extension illusion of the right arm was reduced in the presence of left arm vibration. In Experiment 2, we found that this kinesthetic interaction between the two arms did not occur when the left arm was vibrated in an abducted position. In Experiment 3, the vibration-induced extension illusion of one arm was fully developed when this arm was placed at an abducted position, indicating that the brain receives increased proprioceptive input from a vibrated arm even if the arm was abducted. Our results suggest that proprioceptive interaction between the two arms occurs in a one-arm pointing task when the two arms are aligned with one another. The position sense of one arm measured using a pointer appears to include the influences of incoming information from the other arm when both arms were placed in front of the body and parallel to one another.     

Participant informed consent in cluster randomized trials: review

Background

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.

Conclusions

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.