Access to death certificates: what should research ethics committees require for approval?

PURPOSE: To present and discuss the reactions of research ethics committees (RECs) in a number of countries when asked for approval of a study requiring access to death certificates to identify the physicians signing the certificates and to send them a four-page questionnaire about medical decisions made at the patient's end-of-life that could possibly have hastened death. METHODS: A simple questionnaire were sent to the responsible national investigator in an international study (Australia, Belgium, Denmark, Italy, the Netherlands, Sweden, Switzerland) asking about the interactions between the national research group and the national/regional REC(s). RESULTS: Different laws or guidelines were used by the RECs. Denmark, the Netherlands, and Switzerland did not require an application to a REC. In Australia and Sweden, the RECs wanted changes in the research protocol, and one national research group had to refrain from publishing its results because the attrition rate became too high, probably due to the required changes in the protocol. RECOMMENDATIONS: Generally, similar demands from all RECs in relation to one project are strongly desirable. In epidemiological research, in which voluntary completion of an anonymous questionnaire demonstrates consent, additional prior informed consent about being approached should not be required.     

Written work: the social functions of Research Ethics Committee letters

Research Ethics Committees (RECs) are increasingly institutionalised as a feature of research practice, but have remained strangely neglected by social scientists. In this paper, we argue that analysis of letters from RECs to researchers offers important insights into how RECs operate. We report a traditional content analysis and an ethnographic content analysis of 141 letters to researchers, together with an analysis of the organisational and institutional arrangements for RECs in the UK. We show that REC letters perform three important social functions. First, they define what is deemed by a REC to be ethical practice for any particular application, and confer authority on that definition. They do this actively, through comments on particular aspects of proposals, and passively, through silences about other aspects. Second, they provide an account of the work of the REC, and function as a form of institutional display. Third, they specify the nature of the relationship between the REC and the applicant, casting the applicant in a supplicant role and requiring forms of docility. Writing and reading REC letters require highly specific competences, and engage both parties in a Bourdieusian "game" that discourages challenges from researchers. The authority of RECs' decisions derives not from their appeal to the moral superiority of any ethical position, but through their place in the organisational structure and the social positioning of the parties to the process thus implied. Letters are the critical point at which RECs act on researchers and their projects.     

The Role of Community Advisory Boards: Involving Communities in the Informed Consent Process

Ethical research involving human subjects mandates that individual informed consent be obtained from research participants or from surrogates when participants are not able to consent for themselves. The existing requirements for informed consent assume that all study participants have personal autonomy; fully comprehend the purpose, risks, and benefits of the research; and volunteer for projects that disclose all relevant information. Yet contemporary examples of lapses in the individual informed consent process have been reported. The authors propose the use of community advisory boards, which can facilitate research by providing advice about the informed consent process and the design and implementation of research protocols. These activities could help reduce the number of individual informed consent lapses, benefiting study participants and the scientific integrity of the research in question.     

Research Ethics Committee Auditing: The Experience of a University Hospital

The authors report the first Italian experience of a research ethics committee (REC) audit focused on the evaluation of the REC’s compliance with standard operating procedures, requirements in insurance coverage, informed consent, protection of privacy and confidentiality, predictable risks/harms, selection of subjects, withdrawal criteria and other issues, such as advertisement details and justification of placebo. The internal audit was conducted over a two-year period (March 2009–February 2011) divided into quarters to better value the influence of the new insurance coverage regulation that came into effect in March 2010 (Ministerial Decree of 14 July, 2009) and expand the requirements to safeguard participants in clinical drug trials including other critical items as information and consent and the risks to benefits ratio. Out of a total of 639 REC’s opinions and research studies, 316 were reviewed. Regarding the insurance policy requirements, Auditor/REC non-compliance occurred only in one case. The highest number of Auditor/REC non-compliance was in regard to information and consent, which should have incurred a suspended decision rather than a favorable opinion. This internal audit shows the importance and the difficulty of the review process. For this reason, specific courses for members of the research ethics committee and for those who aspire to become auditors will be provided. There may also be efforts to improve the standard operating procedures already in place.     

Perceptions of potential donors in the Swedish public towards information and consent procedures in relation to use of human tissue samples in biobanks: a population-based study

AIMS: To assess the Swedish public's preferences for information and consent procedures when being asked for permission to use previously collected tissue samples for new research studies. METHODS: Cross-sectional study employing postal questionnaires to a random sample of the Swedish general public (n = 6,000) in October 2002-February 2003. The response rate was 49% (n = 2,928). This paper includes only respondents who reportedly would approve of samples being taken and stored (n = 2,122). RESULTS: When potential tissue sample donors in the general public have to strike a balance between the values at stake, i.e. the autonomy of the donor versus the research value, most (72%) prefer general consent, i.e. where consent is asked for at the outset only. They want the research ethics committee (REC) alone to decide on the use of stored samples, and they would allow storage as long as the sample is useful for research. The minority of respondents who were in favour of specific consent were more likely to be young, well educated, have negative experiences of healthcare and low trust in healthcare authorities. CONCLUSIONS: The majority of the Swedish general public prefer general consent, and are thus willing to delegate some decisions to the RECs. However, preferences for information and consent procedures depend on the context, e.g. the risks for the donor and the purpose of the research. If feasible, procedures should be differentiated according to the preferences of individual donors, thus protecting the interests of both the minority and the majority.     

A consumer perspective on informed consent and third-party issues.

Our two children were diagnosed with a rare genetic disorder, which led us to establish a research foundation. This led to in-depth consideration of issues surrounding informed consent from a consumer perspective. Third-party issues arose as central to the formulation of ethical policy in the establishment of a blood and tissue bank and an epidemiologic study. We suggest that a number of myths--privacy is possible, samples can be stripped of identifiers, humans are subjects, voluntary informed consent is attainable, genetics is about the individual only, genetic information is different than other medical information, research is altruistic, the public will learn truths about genetic research via media, and research is culturally competent--make it difficult to resolve the issues intrinsic to informed consent. A number of important elements could make policy decisions less complicated. These include conducting culturally competent research; conveying noncoercive hope, not hype; contacting the voluntary informant only; asking the informant to extend contact to other family members; requiring a comprehensive informed consent process for all contacted; and engaging in state-of-the-art data protections. There is a need for a "Genomic Hippocratic Oath," creating an ethical basis for research similar to the one vowed by health care professionals. Establishing ethical policies as a result of the collaboration of policy makers, researchers, and consumers will allow research to progress ethically at a rapid rate. If regulations are oppressive, they will thwart research; if they are too lenient, participants will not receive protections needed to participate safely.     

Biobanks and the ‘well-being’ of humanity: integrating consent to research with the capability approach

Among the important ethical challenges that biobanks raise, the shortcoming of the traditional acceptation of informed consent is one of the most debated. The protection of research participants’ autonomy is a central theme in current ethical reasoning on biomedical research. In this article, I argue that moral philosophy offers the opportunity to broaden the debate raised by the shortcomings of the established doctrine of informed consent when applied to biobanking activities. The capability approach and deliberative democracy theories are particularly interesting in analyzing biobanks and informed consent because they shift the focus from the relationships patient/physician and participants in research/investigator–the bioethics focus–to the well-being of research participants and their ability to self-determination understood as a mean by which individuals participate in the societal arrangements that underscore biobanks’ regulation, thus fostering the democratic deliberative process. My claim is that many ethical issues raised are better understood and eventually solved if a broader definition of the notion of autonomy as put forth by moral and political theory is integrated in the discourse of biobanking and informed consent.

Philosophy is like this: eternally unsettled and only occasionally disturbed by new facts

Matt Ridley, Nature via Nurture, p.23     

Dr. Google and Premature Consent: Patients Who Trust the Internet More Than They Trust Their Provider

A growing number of patients make up their minds about some medical issue before they see their provider, either by googling their symptoms or asking a friend. They’ve made up their minds before coming in, and they resist their provider’s recommendations even after receiving information and advice from their provider. This is a new kind of medical autonomy problem; it differs from cases of standard consent, futility, or conscientious refusal. Providers sometimes call this problem “Dr. Google.” I call it premature consent. Providers may wonder whether these patient decisions command the same deference and respect as other patient decisions. The answer is “no,” for these patients are neither fully competent nor properly informed. They typically appear to be competent, but competence includes the ability to deliberate, and they are not deliberating well when they make up their minds before consulting a qualified provider. They seem informed, especially after talking to their provider, but they are misinformed about what sources of medical advice to trust. Moreover, being informed requires believing the information one has received, and these patients sometimes don’t believe the information their provider gives them.     

Research Ethics Committees: can they contribute to the improvement of clinical research in Europe?

There is an increasing crisis of credibility in the world of clinical and epidemiological research because of lack of transparency in the identification of research priorities, increasing dominance of commercial interests over patients' problems, limited funds for independent research, and lack of awareness that clinical research is integral to the duties of clinicians as patients' agents. Research Ethics Committees (RECs) are an important component of the research world and since their institution there are expectations at their ability to protect patients and improve clinico-epidemiological research. To many people, however, the task of RECs is still essentially that of safeguarding the ethical/informed consent issues related to research protocols without a role in the core content (scientific and clinical) of the research projects themselves. Others argue that the duties of RECs should be broader because scientifically invalid research is in itself unethical. The remits of RECs, therefore, should embrace a full range of issues, from assessment of the core content of research (objectives, nonredundancy, clinical relevance, and likelihood of reaching the stated goals) to the protection of publication and dissemination rights of researchers from the intrusiveness of commercial sponsors. This debate is further complicated by current arrangements in countries where RECs' decentralization has made their operation less homogeneous and reproducible, with a diffuse discontent about the end results of their activities. In the first part of the article I discuss the evolution of the concept of the ethics of clinical research and the main differences in the arrangements of RECs across Europe. In the second part, after a brief discussion of the new European Directive on Clinical Trials and its potential problematic impact on publicly-funded trials, I propose a series of actions that should be taken to improve the functioning of RECs and outline the cultural changes needed for research of better methodological quality and of greater relevance to patients.     

Aufgaben und Arbeitsweise Medizinischer Ethik-Kommissionen

In Germany, only Research Ethics Committees (REC) set up according to States law at Faculties of Medicine, Medical Associations or States authorities are entitled to assess all areas of biomedical research. In a multidisciplinary review, research projects are evaluated using the criteria “scientific quality”, “accordance with law” and “ethical acceptability”. Since 2004, the “favorable opinion” of a REC is together with the approval by the competent Federal Authority a legal requirement for drug trials. For all other fields of biomedical research, the opinion of a REC is considered legally not binding advice for the researcher. For sharing of experiences, for harmonization of their work and for partnership with the public, the local-independent RECs established the “Permanent Working Group of German Research Ethics Committees”. This group functions to a certain degree like central RECs in other States.     

Women and cosmetic breast surgery: weighing the medical, social, and lifestyle risks

In this article we provide a comparative analysis of qualitative, semistructured interviews with 24 women who had undergone different forms of cosmetic breast surgery (CBS). We argue that women must negotiate three types of risk: potential medical risks, lifestyle risks connected with choosing "frivolous" self-enhancements, and countervailing social risks affiliated with pressures to maximize one's feminine beauty. In addition, we highlight the challenges faced in negotiating these risks by examining the limits to traditional forms of medical informed consent provided to the women, who received little information on the medical risks associated with CBS, or who were given uncertain and contradictory risk information. Even respondents who felt that they were well informed expressed difficulties in making "wise" choices because the risks were distant or unlikely, and hence easily minimized. Given this, it is fairly understandable that the known social risks of "failed" beauty faced by the women often outweighed the ambiguous or understated risks outlined by medicine. We argue that traditional notions of informed consent and risk awareness might not be adequate for women choosing CBS.     

Informative inducement: Study payment as a signal of risk

In research involving human subjects, large participation payments often are deemed undesirable because they may provide ‘undue inducement’ for potential participants to expose themselves to risk. However, although large incentives may encourage participation, they also may signal the riskiness of a study's procedures. In three experiments, we measured people's interest in participating in potentially risky research studies, and their perception of the risk associated with those studies, as functions of participation payment amounts. All experiments took place 2007–2008 with an on-line nationwide sample or a sample from a northeastern U.S. city. We tested whether people judge studies that offer higher participation payments to be riskier, and, if so, whether this increased perception of risk increases time and effort spent learning about the risks. We found that high participation payments increased willingness to participate, but, consistent with the idea that people infer riskiness from payment amount, high payments also increased perceived risk and time spent viewing risk information. Moreover, when a link between payment amount and risk level was made explicit in Experiment 3, the relationship between high payments and perceived risk strengthened. Research guidelines usually prohibit studies from offering participation incentives that compensate for risks, yet these experiments' results indicate that potential participants naturally assume that the magnitude of risks and incentives are related. This discrepancy between research guidelines and participants' assumptions about those guidelines has implications for informed consent in human subjects research.     

Participants’ understanding of informed consent in clinical trials over three decades: systematic review and meta-analysis

Objective

To estimate the proportion of participants in clinical trials who understand different components of informed consent.

Methods

Relevant studies were identified by a systematic review of PubMed, Scopus and Google Scholar and by manually reviewing reference lists for publications up to October 2013. A meta-analysis of study results was performed using a random-effects model to take account of heterogeneity.

Findings

The analysis included 103 studies evaluating 135 cohorts of participants. The pooled proportion of participants who understood components of informed consent was 75.8% for freedom to withdraw at any time, 74.7% for the nature of study, 74.7% for the voluntary nature of participation, 74.0% for potential benefits, 69.6% for the study’s purpose, 67.0% for potential risks and side-effects, 66.2% for confidentiality, 64.1% for the availability of alternative treatment if withdrawn, 62.9% for knowing that treatments were being compared, 53.3% for placebo and 52.1% for randomization. Most participants, 62.4%, had no therapeutic misconceptions and 54.9% could name at least one risk. Subgroup and meta-regression analyses identified covariates, such as age, educational level, critical illness, the study phase and location, that significantly affected understanding and indicated that the proportion of participants who understood informed consent had not increased over 30 years.

Conclusion

The proportion of participants in clinical trials who understood different components of informed consent varied from 52.1% to 75.8%. Investigators could do more to help participants achieve a complete understanding.     

Expanding the boundaries of previously obtained informed consent in research: Views from participants in the Personalised Risk-based Mammascreening study

Introduction

Understanding participants' concerns and information needs regarding broadened consent is crucial to ensure transparency and participant autonomy. Our study qualitatively examined these issues in women participating in the Personalized RISk-based MAmmascreening study (PRISMA). The original PRISMA informed consent was project-specific (i.e., breast cancer research), limiting the scope of secondary research. We explored participants' needs for broadened consent to preserve informed decision-making while maximising the potential re-use of data.

Methods

Focus groups (FGs) were performed following a semistructured discussion guide. Two independent researchers analysed the data thematically using an inductive approach.

Findings

Twenty-three asymptomatic women and 13 women diagnosed with breast cancer were randomly divided into six FGs. Four superordinate themes were identified: (1) Normalization, (2) Attitude towards the pharmaceutical industry, (3) Privacy and (4) Knowledge. Our participants viewed data sharing as an important conduit for advancing medical science. Perceived integrity was more often attributed to noncommercial than commercial parties, with a marked mistrust towards the pharmaceutical industry. Most requested information needs related to data protection. Participants' ideal consent process would confer a range of options; for example, they would be able to choose with whom data can be shared, whether data will be de-identified or anonymous, the expiration date of their consent and how, if requested, general and personal study results would be disclosed.

Conclusion

Our participants expressed clear information needs and a strong desire to be actively engaged in future data sharing decisions. Given that many researchers collaborate with commercial parties, building public confidence in these institutions would be beneficial. Illustrative examples addressing privacy concerns and clarifying difficult terms would aid consent decision-making. Although our participants displayed great altruism in sharing their data and accepted that broad consent would ultimately facilitate future research, broad consent did not reflect their ideal situation. Dynamic consent may be an option but warrants further feasibility research.

Patient and Public Contribution

Women were recruited from the general breast cancer screening population. Their perceptions and information needs, as reported in this study, will not only inform broadened consent for PRISMA but ideally guide other consent templates and decisions regarding consent processes.     

Doing accountability: a discourse analysis of research ethics committee letters

Research ethics committees (RECs) are charged with adjudicating the ethical status of research projects, and determining the conditions necessary for such projects to proceed. Both because of their position in the research process and because of the controversial nature of ethical judgements, RECs' views and decisions need to be accountable. In this paper we use techniques of discourse analysis to show how REC decision letters 'do' accountability. Using a sample of 260 letters from three datasets, we identify a range of discursive devices used in letters written by RECs. These include drawing attention to: the process behind the decision, including its collaborative nature; holding the applicants accountable, by implying that any decision made by the REC can be attributed to the performance of the applicants; referring to specialist expertise; and calling upon external authorities. These tactics 'do' accountability by showing that routines of ethical assessment have been enacted, by establishing the factuality of claims, and by managing questions of fault and blame attribution. They may, however, also risk undermining legitimacy by failing to acknowledge the inherent contestability of ethical decision making or the limited nature of the cultural authority accorded to RECs, and thus may appear as an illegitimate exercise of power.     

Ethical review from the inside: repertoires of evaluation in Research Ethics Committee meetings

Evaluating the practice of ethical review by Research Ethics Committees (REC) could help protect the interests of human participants and promote scientific progress. To facilitate such evaluations, we conducted an ethnographic study of how an REC reviews research proposals during its meetings. We observed 13 meetings of a Dutch REC and studied REC documents. We coded this material inductively and categorised these codes in two repertoires of evaluation: a repertoire of rules and a repertoire of production. In the repertoire of rules the REC applies rules, weighs scientific value and burdens to the participants and makes a final judgment on a research proposal in a meeting. In the repertoire of production, REC members check documents and forms and advise researchers on how to improve their proposals and can use informal communication. Based on these findings, we think that evaluations of the practice of ethical review should take into account the fact that RECs can use a repertoire of rules and a repertoire of production to evaluate research proposals. Combining these two repertoires can be a viable option so that the REC gives researchers advice on how to improve their proposals to prevent rejection of valuable research.     

Effects of Written Informed Consent Requirements on HIV Testing Rates: Evidence From a Natural Experiment

Objectives. I evaluated the effects of written informed consent requirements on HIV testing rates in New York State to determine whether such consent creates barriers that discourage HIV testing.Methods. New York streamlined its HIV testing consent procedures on June 1, 2005. If written informed consent creates barriers to HIV testing, then New York''s streamlining exercise should have reduced such barriers and increased HIV testing rates. I used logistic regression to estimate the effects of New York''s policy change.Results. New York''s streamlined consent procedures led to a 31.4% (95% confidence interval [CI] = 20.9%, 41.9%) increase in the state''s HIV testing rate. In absolute terms, 7% of the state''s population had been tested for HIV in the preceding 6 months under the streamlined procedures, whereas only 5.3% would have been tested under the original procedures. These estimates imply that the streamlined consent procedures accounted for approximately 328 000 additional HIV tests in the 6 months after the policy change.Conclusions. Written informed consent requirements are a substantial barrier to HIV testing in the United States.There may be a trade-off between efforts to increase HIV testing rates and efforts to improve patient awareness.In 2006, the Centers for Disease Control and Prevention (CDC) endorsed a shift from targeted HIV testing of high-risk groups to broad-based screening of the general population.¹ The CDC called for opt-out HIV screening of all patients in health care settings and argued that written informed consent procedures that are separate and distinct from general consent to medical treatment procedures should not be required for HIV testing.¹ The CDC recommendations reflect concerns that HIV testing rates are too low in the United States because a large number of people do not learn about their infection until it is too late for treatment to be effective.Opt-out screening has increased testing rates in other settings, including genitourinary clinics in the United Kingdom, and there is little doubt that it would increase HIV testing in the general population.^2,3 The effect of informed consent regulations on HIV testing rates is less clear. The CDC claims that such regulations create administrative and social barriers that discourage HIV testing.¹ There is also some evidence that written informed consent regulations represent a legal impediment to the implementation of opt-out testing.⁴ Such concerns might also explain the CDC''s advocacy of informed consent repeal.Critics of the recommendations argue that separate informed consent promotes important ethical and clinical objectives in public health policy and that removing informed consent regulations could lead to a more coercive HIV testing environment.^5–8 In summarizing the controversy, Bayer and Fairchild argued that the CDC''s informed consent recommendations signal an end to the practice of HIV exceptionalism, which leads the medical establishment to approach HIV/AIDS issues differently than it approaches other health conditions.⁹It is difficult to estimate the effects of informed consent regulations on HIV testing rates because variations in state consent requirements may be correlated with state-level characteristics that themselves predict testing rates; that is, state populations are not randomly assigned to different informed consent policies. Zetola et al. reported the best evidence to date. They found that monthly testing rates increased from 13.5 to 17.9 HIV tests per 1000 patients in a set of institutions in San Francisco after that city''s department of public health eliminated written informed consent requirements.⁵ However, the Zetola et al. study lacked a comparison group, which would have alleviated concerns that the increases observed were associated with underlying trends and changes in HIV testing that occurred in the same time frame as the San Francisco policy change.In addition, Zetola et al. relied on administrative data, for which observations were conditional on patients'' visits to particular institutions. It is possible that HIV testing rates among patients who visited these institutions were different than testing rates in the general population. As a result of such problems, it is difficult to generalize the effects of the San Francisco policy change on HIV testing rates in particular institutions to testing rates in the general population.A careful decision on whether to repeal or maintain written informed consent requirements in HIV testing depends on estimates of the effects of the regulations in terms of both testing rates and the physical and psychological risks to patient well-being. It also requires normative judgments regarding the relative importance of these effects in terms of public welfare.¹⁰ In this study, I investigated the CDC''s claim that informed consent regulations lead to reductions in HIV testing rates. I used data from the Behavioral Risk Factor Surveillance System (BRFSS) to examine HIV testing rates in New York State and a set of comparison states before and after the introduction of streamlined HIV test consent procedures in New York. The policy change in New York generated a natural experiment that helps address many of the challenges associated with evaluating the effects of consent procedures on testing rates.     

Do Australian researchers accept committee review and conduct ethical research?

We sought researchers' views on the ethics of research practice and the Australian system of review of research proposals by research ethics committees (RECs). Researchers were found to be supportive of review of research proposals, even though they thought that the process of review was time consuming and demanding. However, our findings suggest that not all researchers present their research proposals for review by committees, and that some researchers deviate from their approved proposals without seeking approval for those deviations from an REC. Researchers supported monitoring of research by RECs.     

Ethics in public health research: protecting human subjects: the role of community advisory boards

Increasingly, researchers grapple with meaningful efforts to involve communities in research, recognizing that communities are distinct from individuals. We also struggle to ensure that individual participants in research are fully protected.Community advisory boards (CABs) offer an opportunity to adopt a relationships paradigm that enables researchers to anticipate and address the context in which communities understand risks and benefits, and individuals give consent. CABs provide a mechanism for community consultation that contributes to protecting communities and fostering meaningful research. Furthermore, CABs can help us to re-create informed consent as a process. It is critical that we conduct research to understand the role of CABs in the informed consent process.     

Differences between research ethics committees

OBJECTIVES: To examine differences in the ethical judgments made by Research Ethics Committees (RECs) or Institutional Review Boards (IRBs). METHODS: We did a review of the literature and included any study that attempted to compare the ethical judgments made by different RECs or IRBs when reviewing one or more protocol. RESULTS: There were twenty-six articles reporting such discrepancies across Europe, within the United Kingdom, Spain, and United States. Of these studies, there were only five reports of some RECs approving while others rejecting the same protocol. All studies, however, reported differences in the clarifications and revisions asked of researchers regarding consent, recruitment, risks and benefits, compensation arrangements, and scientific issues. CONCLUSIONS: The studies were generally anecdotal reports of researchers trying to do research. New rules requiring a single ethical opinion for multi-site research at least in European Member States may simply conceal problematic issues in REC decision making. In the last analysis, we should expect a certain degree of variation and differences if we are to keep a committee system of review, although there is a pressing need to investigate the way in which RECs make these judgments. In particular, we need to identify the source of any aberrations, distortions, or confusions that could arbitrarily affect these judgments. Furthermore, local conditions remain important ethical considerations and should not be sidelined in pursuit of greater "consistency."