Beyond the informed consent procedure: continuing consent in human research

An ethnographic field study about informed consent in hepatitis C clinical trials provides insight into how changes in protocol requirements and patient health status triggered the actions and decisions of researchers and human subjects during the conduct of these trials. U.S. federal guidelines recommend that informed consent should be conceptualized as more than a one-time event. Rather, a process of continuing consent should be the standard but little is understood about how exactly this process should unfold. We used a proposed typology of continuing consent to frame our analysis and were able to document that only some of the proposed types took place at the site of our study. The most frequent practice involved the researchers' re-consent of their subjects for major protocol revisions. Only one subject dissented and chose to withdraw even though he was technically eligible to continue in the study. Two other types of continuing consent were not observed. We discovered an additional type of continuing consent not described in the typology whereby subjects gave implied consent through their cooperation and adherence to the on-going requirements of the protocols. Implications for the informed consent process and the need for further research are presented.     

Informed consent in clinical trials

A review is provided in this paper on the empirical literature on informed consent from 1979 to 1995 referring to information disclosure and trial participation in clinical trials. Articles being reviewed focus upon information disclosure, reactions to disclosure and recall, features of consent and perceptions of informed consent, both in hypothetical and in real life situations. It is concluded that further research is needed to study the process of informed consent in clinical trials, to obtain a better insight into the myth and reality of informed consent in daily practice. Future studies should come forward on the limitations of previous empirical research on informed consent. Additional research should focus on the perspectives of patients who accept or decline trial participation.     

Empty ethics: the problem with informed consent

Informed consent is increasingly heralded as an ethical panacea, a tool to counter autocratic and paternalistic medical practices. Debate about the implementation of informed consent is constricted and polarised, centering on the right of individuals to be fully informed and to freely choose versus an autocratic, paternalistic practice that negates individual choice. A bioethical framework, based on a principle-led form of reductive/deductive reasoning, dominates the current model of informed consent. Such a model tends to abstract the process of consent from its clinical and social setting. By flashing out the social process involved when patients and healthy volunteer subjects consent to take part in clinical drug trials, this paper attempts to address the problem arising from the current 'empty ethics' model. My arguments are substantiated by qualitative interview data drawn from a study I conducted on the process of consent as experienced by participants in clinical drug trials.     

Conducting research in developing countries: experiences of the informed consent process from community studies in Peru

This article discusses the process for obtaining genuine informed consent for the participation of human subjects in research in developing countries. We discuss the consent process in the light of recently published guidelines, the experience of nutrition and health research projects, and the ethics review process of the Instituto de Investigacion Nutricional with peri-urban and rural populations in Peru. We discuss the cultural context in relation to (i) who should be involved in the decision for participation, especially for research in children and in community settings; (ii) when to use written or verbal consent; (iii) the format and presentation of the consent form to ensure understanding by the target population; and (iv) the process of how and by whom information is given and consent is obtained. Common concerns of participants with regard to their involvement in research studies are presented, as well as aspects that participants find difficult to understand. Some specific concerns of conducting research with Indigenous Peoples are discussed. We recommend future research to further understand and implement informed consent processes to assure genuine and voluntary consent in different developing country contexts.     

Reasons why patients do or do not participate in clinical trials; a systemic review of the literature

OBJECTIVE: To assess the factors that may influence a patient's consent to participate in a clinical trial. DESIGN: Systematic literature survey. METHOD: Studies on the characteristics of patients, trials, the physicians requesting informed consent and the informed consent procedures were looked for in Medline, Embase, and Cinahl. Articles published in English, German, Dutch or French in the period 1980-2002 and originating in Europe, the United States, Canada, New Zealand or Australia were included. Studies on non-adults, healthy experimental subjects or less than 30 patients were excluded. RESULTS: Thirty suitable studies were retrieved. Factors that may affect the granting of consent to participate in a clinical trial included: uncertainty of the patient, randomisation and the use of a placebo, the relationship between the person asking for informed consent and the patient, and the dissemination of information during the informed consent procedure. Since these factors are often interrelated, no single factor could be identified as decisive for participation in a clinical trial; they can influence the decision of the patient to participate in a trial in either a positive or a negative direction. CONCLUSION: Optimalization of the information concerning informed consent, the way the information is provided and the attitude of the person requesting informed consent are important and sometimes decisive factors that may determine the participation process.     

Accrual to cancer clinical trials: directions from the research literature

Although randomized clinical trials are the predominant method used to evaluate cancer therapies, only a small proportion of potential participants actually enter onto trials. This paper analyzes the research literature on accrual to cancer therapy trials. The research shows that nonparticipation is influenced by physician and patient variables, as well as by characteristics of the specific protocols. Trials design, especially pre-existing treatment preferences, pose significant problems for physicians and patients. Intervention strategies have focused on alternate trial designs, improving the informed consent process, and increasing knowledge about trials. Additional research should focus on the perspectives of patients who accept and decline trial participation and on interventions designed to affect accrual. Future studies need to be sensitive to patient quality of life considerations as well as practical and ethical issues.     

It's not just what you say,it's also how you say it: Opening the ‘black box’ of informed consent appointments in randomised controlled trials

Randomised controlled trials (RCTs) represent the gold standard methodology for determining effectiveness of healthcare interventions. Poor recruitment to RCTs can threaten external validity and waste resources. An inherent tension exists between safeguarding informed decision-making by participants and maximising numbers enrolled. This study investigated what occurs during informed consent appointments in an ongoing multi-centre RCT in the UK. Objectives were to investigate: 1] how study staff presented study information to participants; 2] what evidence emerged as to how well-informed participants were when proceeding to randomisation or treatment selection; and 3] what aspects of the communication process may facilitate improvements in providing evidence of informed consent. Qualitative analysis of a purposive sample of 23 recruitment appointments from three study centres and involving several recruitment staff applied techniques of thematic, content and conversation analysis (CA). Thematic analysis and CA revealed variation in appointment content and structure. Appointments were mostly recruiter-led or participant-led, and this structure was associated with what evidence emerged as to how participants understood information provided and whether they were in equipoise. Participant-led appointments provided this evidence more consistently. Detailed CA identified communication techniques which, when employed by recruiters, provided evidence as to how participants understood the choices before them. Strategic use of open questions, pauses and ceding the floor in the interaction facilitated detailed and systematic exploration of each participant's concerns and position regarding equipoise. We conclude that the current focus on content to be provided to achieve informed consent should be broadened to encompass consideration of how information is best conveyed to potential participants. A model of tailored information provision using the communication techniques identified and centred on eliciting and addressing participants' concerns is proposed. Use of these techniques is necessary to make potential participants' understanding of key issues and their position regarding equipoise explicit in order to facilitate truly informed consent.     

Inquiry into the potential value of an information pamphlet on consent to surgery to improve surgeon-patient communication.

OBJECTIVES: To find out how patients recently undergoing surgery experienced the consenting process and the response of these patients to a pamphlet on consent to surgery. To test the reaction of health professionals to the pamphlet. DESIGN: A pilot pamphlet was produced and a questionnaire was sent to patients inquiring about their consenting experience, and how the pamphlet might have helped them through the consent procedure. A pamphlet and a questionnaire were also sent to a random sample of the health professionals serving these patients. SUBJECTS: Patients and health professionals. RESULTS: 61% of patients returned the questionnaire. Knowledge about the consent procedure was shown to be limited. 49% were unaware that they had the right to insist that the surgeon could only perform the specified operation and nothing more. 83% were unaware that they could add something in writing to the consent form before signing. 28% of health professionals returned their questionnaire, most of whom thought that the pamphlet provided a useful contribution to surgeon-patient communication. CONCLUSION: Evidence shows that patients are not well informed about consenting to surgery and further information would provide much needed guidance on understanding their role in the consent procedure. The low response from the health professional study is perhaps an indication that at present this is an issue which is not seen as a priority.     

Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study.

The use of more than 130 drugs and drug combinations against the alcohol withdrawal syndrome reflects the fact that views on its treatment are far from being unequivocal. Benzodiazepines are the first choice treatment but it should not be disregarded that they have side effects and, above all, a varying risk of dependency themselves. In recent years many trials have focused on carbamazepine in this respect. Its efficacy was proven in various open and double-blind studies, most of them using concomitant sedative drugs, thereby diminishing the reliability of the results. In a double-blind study we compared the efficacy of carbamazepine with that of oxazepam, in 60 in-patients suffering from alcohol withdrawal syndrome. The main rating instrument was the Clinical Institute Withdrawal Scale--Alcohol (CIWA-A). The 7-day trial showed equal efficacy of carbamazepine and oxazepam during the first 5 days and a statistically significant superiority of carbamazepine on days 6 and 7. Four patients in each group had to be dropped from the study due to side effects or after having withdrawn informed consent. There was no decrease in white blood counts under carbamazepine. The experiences with carbamazepine up to now suggest a more widespread use, especially in non-delirious withdrawal states.     

The rights of psychiatric patients in China: a survey of medical staff and consumers' attitudes toward patient participation in clinical trials

To explore and compare attitudes of consumers (patients and their family members) and medical staff toward clinical trials related to mental health in China, we developed two questionnaires for medical staff and patients and their family members. Approximately 66.2% of medical staff who had no research experience believed that patients could be persuaded to participate in clinical trials, but the percentage of consumers who believed so was just 12.5%. Both groups agreed that written informed consent was required; however, more medical staff than patients agreed that such consent could be provided by patients or their guardian (88.4% vs. 71.4%). Only 9.5% of medical staff thought that patient treatment would be compromised by refusal to participate; the proportion of consumers who thought the same was 29.4%. Great differences exist between medical staff and consumers' attitudes and beliefs regarding clinical trials. Medical staff were more likely to have a favorable attitude toward their patients participating in clinical trials and considered that informed consent could be provided by guardians rather than the patient.     

The patient's right to information in Japan--legal rules and doctor's opinions

A questionnaire survey concerning informed consent was administered among Japanese physicians in Yamaguchi prefecture. The survey results showed that even though these Japanese physicians are willing to give their patients sufficient information to obtain informed consent, the discretion of the physician to provide information is still prevalent. The survey also revealed that Japanese physicians believe that information regarding the treatment to be administrated should be fully disclosed both in case when the treatment is still experimental and when it is established among specialists. Finally, the survey showed that despite the liberal attitude of the Japanese physicians toward informed consent, they are reluctant to make medical records accessible to the patients. It was found that when Japanese physicians were faced with special cases such as prior to administering high-risk diagnostic procedures, prior to disclosing the presence of cancer in their patients, or when faced with patients unwilling to receive treatment, the involvement of the patient's family members in the decision-making process was preferred so as not to aggravate the patient's emotional anxiety. With respect to cancer patients, the survey suggested that many Japanese physicians believe that cancer operations performed without informed consent from the patient should be legal. Finally, the survey concluded that, although the concept of individualized informed consent has been generally accepted among physicians, the involvement of family members in the decision-making process and a conservative attitude toward disclosure of information are still prevalent in Japan.     

Consent and clinical governance: improving standards and skills

Obtaining appropriate and informed consent from patients is an integral part of provision of quality health care. Doctors are bound to obtain consent in a manner that is legally and ethically acceptable. The methods employed to train junior doctors in these principles vary from organisation to organisation and the knowledge base of both senior and junior clinicians is far from consistent. This paper raises some of the issues in relation to current practice and teaching and suggests ways in which the process can be improved--largely by introducing some basic standards that should be built on as expertise and skill develop. The author discusses the need for dissemination of information with regard to current national claims experience and the possibility of introducing the subject of consent into postgraduate examinations in a more widespread way.     

Quantifying and documenting prior beliefs in clinical trials

Collecting and documenting subjective prior beliefs from knowledgeable clinicians about the potential results of a clinical trial has many advantages. Two large trials of prophylactic treatments in an HIV-positive population are used as examples. The trials recruited patients of primary care physicians and compared treatments which were in use in clinical practice. Opinions about these trials were elicited from 58 practising HIV clinicians. It is shown how the documented opinions can be used to augment the monitoring process; the prior opinions are updated with interim data using approximate Bayesian methods to give posterior opinions incorporating interim results. These posterior opinions can be used by the monitoring board to anticipate the clinicians' reaction to the results. Eliciting prior beliefs is also ethically important for documenting the nature of the uncertainty or equipoise. Important information is provided for the informed consent process and Institutional Review Board (IRB).     

药物临床研究中痴呆受试者知情同意过程探析

目的为我国痴呆药物临床研究受试者知情同意的规范化提供参考依据。方法对近年来我院关于痴呆药物的临床研究知情同意过程中所存在的问题及其原因进行分析,探究其解决方法。结果随机双盲安慰剂对照研究或针对中重度痴呆患者的研究中,受试者及其知情者的知情同意过程困难,不良事件发生率高,反之随机双盲阳性药对照或轻度痴呆患者的研究上述情况则较少出现。结论建议通过对受试者、知情者的健康教育及对研究者的法制教育,构造完善的法律法规保障制度,健全伦理委员会监督机制等措施来保护受试者及其知情者的权益。     

Health literacy, self-efficacy, and patients' assessment of medical disclosure and consent documentation

Informed consent documents are designed to convey the risks of medical procedures to patients, yet they are often difficult to understand; this is especially true for individuals with limited health literacy. An important opportunity for advancing knowledge about health literacy and informed consent involves examining the theoretical pathways that help to explain how health literacy relates to information processing when patients read consent forms. In this study, we proposed and tested a model that positioned self-efficacy as a mediator of the association between health literacy and patients' comprehension and assessment of informed consent documentation. Findings from structured interviews with patients (n?=?254) indicated that lower health literacy predicted lower self-efficacy, which predicted feeling less well informed and less prepared, being more confused about the procedure and its hazards, and wanting more information about risks. Incorporating awareness of self-efficacy into disclosure documents and consent conversations may be a useful means of prompting patients to ask questions that can help them make informed decisions about care.     

Health Literacy,Self-Efficacy,and Patients' Assessment of Medical Disclosure and Consent Documentation

Informed consent documents are designed to convey the risks of medical procedures to patients, yet they are often difficult to understand; this is especially true for individuals with limited health literacy. An important opportunity for advancing knowledge about health literacy and informed consent involves examining the theoretical pathways that help to explain how health literacy relates to information processing when patients read consent forms. In this study, we proposed and tested a model that positioned self-efficacy as a mediator of the association between health literacy and patients' comprehension and assessment of informed consent documentation. Findings from structured interviews with patients (n?=?254) indicated that lower health literacy predicted lower self-efficacy, which predicted feeling less well informed and less prepared, being more confused about the procedure and its hazards, and wanting more information about risks. Incorporating awareness of self-efficacy into disclosure documents and consent conversations may be a useful means of prompting patients to ask questions that can help them make informed decisions about care.     

Some Popular Versions of Uninformed Consent

A patient's informed consent is required by the Nuremberg code, and its successors, before she can be entered into a clinical trial. However, concern has been expressed by both patients and professionals about the beneficial or detrimental effect on the patient of asking for her consent. We examine advantages and drawbacks of popular variations on consent, which might reduce the stress on patients at the point of illness. Both informed and uninformed responses to particular trials, and trials in general, are discussed. The selection by doctors of patients, to whom entry to trials will be offered, is explored.Alternative forms of consent require restrictions on patients' knowledge, personal responsibility and freedom of choice.     

'Informed consent' and prerandomization

The usual procedure in randomised controlled trials is to obtain informed consent first, after which participants can be randomised. The reversal of the order, first randomisation and then informed consent, is called pre-randomisation (Zelen design). In the Netherlands, there is discussion as to whether pre-randomisation should be allowed in medical research. Full informed consent regarding the design of the investigation may lead to unwanted loss of distinction between the experimental and control groups, thus reducing the internal validity of the investigation. A possible solution could be to include, in the informed consent procedure, the statement that certain information has been withheld because revealing it now would make the investigation useless, but that it will be revealed to all participants afterwards and that the study design was approved by the medical ethics committee. In this way, the advantage of the enhanced internal validity of the pre-randomisation design is retained while simultaneously keeping intact the sequence of first informed consent and then randomisation.     

Mandatory PKU screening: the other side of the looking glass.

The challenge that PKU screening programs face is to be effective without sacrificing individual liberty. Most states have assumed that this is impossible, and have enacted mandatory PKU screening tests. It now appears that in fact voluntary screening for PKU can be effective. Accordingly, it seems appropriate to reexamine existing mandatory screening statutes to determine if we can replace government coercion with voluntary informed consent. Focus should be placed on the proper role of the government in screening, and on improving the consent process, and not on those few couples who withhold consent.