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Family experiences with non-therapeutic research on dying patients in the intensive care unit
  1. Amanda van Beinum1,2,
  2. Nick Murphy3,
  3. Charles Weijer4,5,
  4. Vanessa Gruben6,
  5. Aimee Sarti7,8,
  6. Laura Hornby1,9,
  7. Sonny Dhanani1,10,
  8. Jennifer Chandler6,11
  1. 1 Critical Care Research, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
  2. 2 Sociology and Anthropology, Carleton University Faculty of Arts and Social Sciences, Ottawa, Ontario, Canada
  3. 3 Philosophy, Western University, London, Ontario, Canada
  4. 4 Philosophy, Western University Faculty of Arts and Humanities, London, Ontario, Canada
  5. 5 Medicine, Epidemiology and Biostatistics, Western University Schulich School of Medicine and Dentistry, London, Ontario, Canada
  6. 6 Common Law, University of Ottawa Faculty of Law, Ottawa, Ontario, Canada
  7. 7 Medicine, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
  8. 8 Critical Care Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
  9. 9 Deceased Donation, Canadian Blood Services Organ Donation and Transplantation, Ottawa, Ontario, Canada
  10. 10 Division of Pediatric Critical Care, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  11. 11 Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
  1. Correspondence to Amanda van Beinum, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada; avanbeinum{at}cheo.on.ca

Abstract

Experiences of substitute decision-makers with requests for consent to non-therapeutic research participation during the dying process, including to what degree such requests are perceived as burdensome, have not been well described. In this study, we explored the lived experiences of family members who consented to non-therapeutic research participation on behalf of an imminently dying patient.

We interviewed 33 family members involved in surrogate research consent decisions for dying patients in intensive care. Non-therapeutic research involved continuous physiological monitoring of dying patients prior to and for 30 min following cessation of circulation. At some study centres participation involved installation of bedside computers. At one centre electroencephalogram monitoring was used with a subset of participants. Aside from additional monitoring, the research protocol did not involve deviations from usual end-of-life care.

Thematic analysis of interviews suggests most family members did not perceive this minimal-risk, non-therapeutic study to affect their time with patients during the dying process, nor did they perceive research consent as an additional burden. In our analysis, consenting for participation in perimortem research offered families of the dying an opportunity to affirm the intrinsic value of patients’ lives and contributions. This opportunity may be particularly important for families of patients who consented to organ donation but did not proceed to organ retrieval.

Our work supports concerns that traditional models of informed consent fail to account for possible benefits and harms of perimortem research to surviving families. Further research into consent models which integrate patient and family perspectives is needed.

  • informed consent
  • research ethics
  • research on special populations
  • death
  • vital organ donation

Data availability statement

All data relevant to the study are included in the article.

http://dx.doi.org/10.1136/medethics-2021-107311

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    Introduction

    Non-therapeutic research involving imminently dying patients in the intensive care unit sits at an intersection between the research domains of critical care, palliative care and postmortem investigations. Important research questions—such as when and how death occurs amidst life-supporting technology,1 2 how best to accurately and safely determine death using clinical tests and diagnostics3 and how to optimise processes of deceased organ donation4—can only be answered through close study of the dying process and, at times, interventions on the imminently dying patient.

    The ethics of research on dying patients have been discussed primarily in the context of palliative care, in which death is expected and dying takes place gradually over weeks or months.5–7 In contrast, perimortem research in the intensive care unit often occurs in circumstances of sudden, unexpected illness or injury which renders patients unconscious and at risk of death within hours or days of hospital admission. Both therapeutic and non-therapeutic research procedures conducted in these contexts require surrogate consent, in which an authorised substitute decision-maker is permitted to make decisions about research participation on a patient’s behalf.8–11 Non-therapeutic perimortem research in these settings must also contend with practical and ethical challenges in several areas, including constraints on resources,12 13 the conduct of research procedures during important life transitions,14 15 gatekeeping by research ethics committees,16–18 conflict with clinical processes such as organ and tissue donation1 and the need to engage substitute decision-makers amidst the stressful context of critical illness.19–21 In addition, study designs are often met with resistance from grant reviewers, research ethics committees and site investigators who may lack experience and comfort with non-therapeutic research on imminently dying patients.22–24

    Unconscious and imminently dying patients cannot provide consent, nor can they directly report experiences of physical or emotional harms or benefits. Nevertheless, the possibility of harm to both patients and surviving family exists even with minimal-risk non-therapeutic research.25 Some researchers proposing perimortem studies have suggested that because potential harms are minimal in comparison with assumed burdens of surrogate decision-making, a waiver of the consent requirement is justified.26 Others have advocated for the need for informed consent from families as part of the recognition of both the intrinsic human dignity of the dying patient and the social significance of the dying process.27 Stakeholder engagement indicates support for a process of informed consent prior to enrolment of imminently dying patients.22 28 However, the experiences of substitute decision-makers with requests for research consent and non-therapeutic research participation during the dying process, including to what degree such consent requests are perceived as burdensome, have not been well described.

    In this study, we explore the lived experiences of substitute decision-makers who consented to non-therapeutic research participation on behalf of an imminently dying family member.

    Methods

    We present an analysis of interview data obtained as part of a larger qualitative investigation of family experiences of decision-making about end-of-life care and organ donation after circulatory determination of death. The qualitative project was one component of a prospective, international observational study on the process of dying following withdrawal of life sustaining measures in the intensive care unit.2

    Research context

    The Death Prediction and Physiology after Removal of Therapy study has been described in detail elsewhere.2 Here we provide an overview of study procedures as a background for reported family experiences.

    Observational data were collected from adult patients (≥18 years of age) in the intensive care unit during the withdrawal of life sustaining measures, the subsequent dying process and for up to 30 min after cessation of circulation. Study procedures required a research coordinator to obtain the patient’s electronic waveform data from existing electrocardiogram (ECG), arterial line and pulse oximeter devices. Data were obtained from existing bedside monitors during the dying process, either using a direct laptop connection in the patient’s room (installed during the study), or by downloading it from a central monitor. At one centre, study procedures involved the addition of an electroencephalogram (EEG) to monitor brain activity. Setting up the EEG sometimes involved a delay in the timing of the removal of life sustaining measures to permit the placement of electrodes on the patient’s scalp and connection to additional monitors at the bedside. All imminently dying patients in the intensive care unit with pre-existing continuous monitoring of blood pressure and heart rate, including potential organ donors, were eligible for enrolment. Patients declared dead using neurological criteria were ineligible. The study was designed so as not to interfere with routine end-of-life care.

    Informed consent was obtained from patients’ substitute decision-makers before withdrawal of life sustaining measures and commencement of data collection. At eight Canadian sites, families who agreed to the observational study were then asked if they were willing to be contacted after the patient’s death about participation in this interview study.

    Semi-structured family interviews

    Participating families who agreed to follow-up were contacted by phone 6 months to 1 year following the patient’s death regarding participation in a semi-structured interview. This time window was suggested by the research ethics boards reviewing our study. We did not restrict study participation to the surrogate decision-maker; all family members who had been involved in the dying process were invited to participate. After three unsuccessful attempts to reach a family member they were considered lost to follow-up. If a family member agreed to participate, the study team sent a copy of the informed consent form by mail or email and set up a time for the interview. A member of the research team reviewed the consent form with each participant prior to commencing the interview. All interviews were conducted by phone or in-person, digitally audio recorded, and transcribed verbatim. Interviews consisted of questions about family experiences surrounding decision-making in the intensive care unit, including the decision to withdraw life sustaining measures, the decision to consent to or decline organ donation and the decision to participate in research. Questions were designed to explore connections between decisions as well as interactions among family members and the healthcare team. The analysis presented here is focused specifically on aspects of interviews pertaining to research decision-making and participation (online supplemental material).

    Supplemental material

    Interview transcripts were analysed using Atlas.ti.29 AvB, JC, VG and AS read and coded five transcripts, meeting after each transcript to develop a coding guide. Once a final coding guide was developed, AvB, JC, VG and AS read and coded subsets of transcripts. Each transcript was reviewed and coded by two researchers. AvB then read through all transcripts to ensure coding consistency and met with other authors to resolve any discrepancies. We used an iterative and applied method of constant-comparative coding30 31 to compile thematic understandings related to family experiences of consent and participation in prospective perimortem research in the intensive care unit.

    Results

    Forty-eight families who provided consent for a patient to participate in perimortem research were eligible for a follow-up interview and agreed to be contacted. Eight (8/48, 17%) family members declined to be interviewed when contacted, and 12/48 (25%) were lost to follow-up. Twenty-eight out of 48 (58%) families agreed to participate and completed an interview. Of participating families, 24/28 (86%) consented to organ donation (of whom 11/24 (46%) proceeded to organ recovery), 2/28 (7%) declined organ donation and 2/28 (7%) made decisions on behalf of patients who were not eligible for organ donation.

    A total of 33 individual family members participated in an interview (two families included multiple members in the interview process). Participants were 70% women (23/33) and were most often the sibling (10/33, 31%), spouse (9/33, 27%) or parent (8/33, 24%) of the deceased. One family at one study site consented to the addition of EEG monitoring during the dying process; this interview is labelled accordingly.

    Difficulty remembering approach for consent to research

    Almost half (16/33, 48%) of participants expressed at some point during the interview that they did not clearly remember agreeing for their family member to participate in a research project (table 1). Participants described being ‘in a fog’ (Interview 45) during the process of their loved one dying in the intensive care unit. As a result, many memories were unclear (“it was all kind of blurry” (Interview 42)). Several participants explained that this was likely due to their focus elsewhere—on the process of withdrawal of life sustaining measures, organ donation or both (“I was consumed with other things.” (Interview 8)).

    View this table:
    Table 1

    Difficulty remembering approach to research

    Experiences of consenting to research

    Fourteen out of 33 (42%) participants had some memory of signing a consent form (table 2). Several participants explained that they gave ‘permission’ for researchers to have access to the dying patient. As one family member explained, “nothing was done [to the patient] unless we gave permission,” (Interview 16, patient had EEG monitoring). Participants most commonly described the consent process as another form to be signed, part of the ‘paperwork’ involved in making a decision for withdrawal of life sustaining measures and consenting to deceased organ donation. Many did not appear to separate these as distinct decisions. Instead, decisions to withdraw life sustaining measures, consent for organ donation and requests for participation in research blended together in their memories of the experience, as did the various medical personnel involved in those conversations. As one participant noted, “You know I signed so many papers that night. You know, I remember signing, I remember them just saying, do you want to participate in a survey, you know, I don’t remember what the name of it was and I had said yes. They may have told me and I’m sure they did. It’s just, at that point you have to sign like hospital papers and the funeral home. So honestly, no, I don’t remember any of it,” (Interview 27).

    View this table:
    Table 2

    Experiences of consent

    During the interviews some participants reflected on their perceptions of the risks and benefits of consenting to this prospective perimortem study. Participants perceived the observational study to be minimally invasive (ie, not requiring additional blood draws or research procedures), which contributed to their decision to provide consent (table 2). No family members expressed concern with the requirement for continued monitoring after death. The family that consented to the addition of electroencephalogram monitoring also reported similar experiences of not finding the research to be unduly invasive or obtrusive.

    Reasons for consenting to research

    We asked all participants, even those who could not distinctly remember the process of being approached for and providing informed consent, to reflect on why they had agreed for their dying family member to participate in perimortem research (table 3). Common themes included the desire to help others, to contribute to the advancement of science, and the desire to create meaning from the patient’s death. Many family members said that consenting to research participation was in line with the patient’s personal values and was something they had previously mentioned or likely would have agreed to. The wife of one patient told us, “It was one of M’s wishes always to be part of the research […] Whether it be even for, like… He used to joke about being a lab rat. Like, he said as long as his body is reused for a useful purpose, whether it be for schooling/teaching or someone was a recipient, that’s what he wanted to do,” (Interview 46). In contrast, some family members explained that consenting to research participation was in line with their own personal beliefs about the value of research and helping others, including several participants with personal experience in research-related work. One patient’s son explained, “I guess as a researcher I recognise the importance of data; this kind of data is particularly hard to get, I would suspect,” (Interview 33). We did not observe any family members who consented to research in a manner that appeared to conflict with the patient’s pre-stated desires. Family members justified their consent to perimortem research as upholding the patient’s and their own personal values.

    View this table:
    Table 3

    Reasons for consent

    Experiences of research procedures

    Several family members’ reflections on the patient’s research participation suggested that they may have had difficulty distinguishing processes of clinical care and organ donation from research (table 4). Participants remarked that there were ‘so many people, and so many names’, (Interview 23), involved at the end of the patient’s life that research processes ‘just felt like [part of] the flow of what was happening, they were just a part of that’, (Interview 35–3). Participants did not perceive this confusion of roles negatively.

    View this table:
    Table 4

    Experiences of research procedures

    Family members who remembered research participation did not appear to have perceived it to be invasive or to have greatly impacted their ability to be with the patient during the dying process. Several commented on how kind and professional the research team was (table 4). Others experienced the patient’s research participation more ambivalently, describing the collection of observational data as something that was ‘going to be done”, (Interview 3) or something that ‘had to be done’ (Interview 33).

    A few participants explained that their experiences of witnessing the patient’s participation in research were overshadowed by their focus on organ donation and honouring the patient’s wishes for end-of-life care. One participant said: “[the research process] was okay, we weren’t there for the monitors, we were there for B, to say our goodbyes, I mean, it wasn’t, we just pretended it wasn’t there… it wasn’t an invasion of privacy or anything like that, it was there, yeah,” (Interview 16, patient had EEG monitoring). This same participant later explained that since the research was a way to honour the patient’s memory, the procedures were not perceived as intrusive: “…for our family, it wasn't intrusive, and I know some would possibly think that, but for us it wasn't, because of the nature of B’s personality, and just what we knew of him, and we did what we thought was, the best thing we could to honor him,” (Interview 16, patient had EEG monitoring). Another participant framed this sentiment in terms of how they personally felt about research, stating that their “logical and fact-based mind” (Interview 33) allowed them to perceive the research as not obtrusive and instead contributing to a larger project of knowledge acquisition. None of the participants experienced their loved one’s participation in perimortem research negatively.

    Discussion

    Our interviews with 33 family members represent one of the largest descriptive cohorts to date of decision-maker experiences with non-therapeutic research on dying patients. Our thematic analysis suggests that most family members did not perceive participation in this observational research study to encroach on their time with the patient during the dying process. Similar themes were reported across interviews with family members who consented for the addition of neurological monitoring during the dying process and those who declined consent for organ donation. Qualitative insights from this study are consistent with high rates of consent observed in recent minimal-risk, non-therapeutic perimortem research in critical care populations.2 24

    We observed that many substitute decision-makers did not have clear memories of being approached for and consenting to the study beyond the experience of signing a consent form. Burns and colleagues similarly report that substitute decision-makers had a poor ability to recall details of the consent approach but were nevertheless able to comment on reasons for the consent decision.32 Difficulty remembering the details of research consent may be due in part to the emotionally and physically demanding circumstances faced by family members of imminently dying patients.33

    Our results support prior assertions that informed consent for perimortem research offers an important opportunity for families of the dying to affirm the intrinsic value of the patient’s life and contributions.28 In our study, whether family members provided consent for altruistic reasons or due to known research-related wishes of the patient, the act of providing consent for research allowed grieving families to feel that the patient had made a positive contribution to the advancement of scientific and medical knowledge. Though not all participants recalled signing the consent form when asked open-ended questions about their experiences of research, on reflection all were able to provide reasons for why they had agreed to the patient’s participation. Altruism and a belief in the value of research align with previous studies of substitute decision-maker’ research decisions in the intensive care unit.34

    The opportunity to create meaning through research consent and participation may have been particularly important for families of patients who consented to organ donation but were not able to proceed to organ retrieval. As the wife of a patient who was ultimately unable to donate organs described, “So, and in the end. That was A. He was so, he was so interested in data and research and teaching that if we couldn’t have donated you know, his organs, at least something was given back to science, which I’m very grateful for…” (Interview 20). Contrary to suggestions that prospective consent for minimal risk research on the imminently dying may be burdensome,20 we found that families often attributed meaning to the ability to ‘give back’ through research participation. Removing this possibility by adopting a waiver of consent approach may in some cases deny a benefit to patients and families.

    Some participants appeared to have difficulty distinguishing between research, organ donation procedures and routine clinical care . While no family members indicated they thought research participation would benefit the patient (ie, none operated under a therapeutic misconception35 36), the inability to separate these distinct activities may limit families’ ability to ask questions or voice concerns about research. Proximity in timing of consent for research and organ donation may also suggest to families (incorrectly) that one is not possible without the other. We did not explore this theme in our interviews and we believe this merits further investigation.

    The possibility for meaning-making and the risk of procedural confusion by families point to the need to rethink traditional autonomy-based foundations of informed consent in perimortem research designs. Death is a biological as well as a social process, one which impacts families in complex ways.37 Consent models built on assumptions of patient autonomy and individual atomism may fail to account for the involvement of family members and ‘intimate others’38 in surrogate decision-making in perimortem research. Indeed, even outside the context of perimortem research, traditional conceptions of autonomy have led to debates about how substitute decision-makers should make decisions on behalf of others (ie, use of substituted judgement vs best-interests models).39–42

    More recently, feminist and ethics of care criticism of the traditional notion of autonomy have led to the development of relational autonomy models for use in decision-making.43 Grignoli and colleagues argue that relational autonomy—a model that emphasises the importance of relationships for autonomy and its exercise—may provide a better ethical framework for evaluating decision-making processes in critical care where patient autonomy is often compromised and families assume much of the decision-making burden.44 Rather than focusing criticism on the degree to which the previously expressed wishes and values of the patient are upheld by consent procedures, relational autonomy models strive to account for how patients’ lives hold meaning and value for—and in relation to—others45 In the context of non-therapeutic perimortem research, the benefits and risks of participation are shouldered mainly by surviving family since the patient’s death is imminent.25 46 As a result, we believe that relational autonomy may usefully inform consent processes in non-therapeutic, perimortem research.47 A relational autonomy perspective would uphold the intrinsic value, personhood and contributions of the patient. In addition, this perspective would allow space for family meaning-making in the dying process. Where possible, perimortem research should seek to partner with the family as part of research design,48 as well as to consider how research interventions, even in minimal risk studies, pose risks and benefits to families which include, but are not limited to, the approach for consent.

    Limitations

    This study has a number of limitations. There was a 6-month to 12-month interval between patients’ deaths and family member interviews. Researchers have recently outlined the benefits of a less paternalistic approach which permits bereaved families to decide for themselves when to be contacted.49 It is likely that this time interval led to more difficulties remembering details about the study, the consent processes and family members’ time in the intensive care unit. However, all participants were asked to reflect on why they consented to perimortem research and how they felt about it, allowing us to elucidate a number of themes.

    The minimally invasive nature of the perimortem research may have contributed to family members’ unclear memories as well as their positive or ambivalent perceptions of research procedures. In addition, it is likely that family members who agreed to complete an interview already held positive views about research. Caution should be taken not to over-generalise the findings of our study.

    Finally, we did not interview research coordinators, organ donation coordinators or bedside staff who interacted with family members. The perspectives of medical personnel would provide important context and nuance to understanding how processes of informed consent and prospective perimortem research take place during end-of-life care in the intensive care unit.

    Conclusion

    Our interviews with family members about their experiences of perimortem research contribute further evidence that obtaining surrogate consent is feasible and that some non-therapeutic research procedures are not perceived as intrusive. Rather than being perceived as a burden, requests for consent for perimortem research offer families the opportunity for meaning-making during the dying process. Models of informed consent based on traditional views of autonomy may fail to account for potential benefits and risks that perimortem research poses to families. Relational autonomy may be better suited to low risk non-therapeutic perimortem research designs.

    Data availability statement

    All data relevant to the study are included in the article.

    Ethics statements

    Patient consent for publication

    Ethics approval

    This study was approved by the University of Ottawa Social Sciences and Humanities Research Ethics Board (file no. 04-15-25) and by the local research ethics board of all participating centres: St Michael’s Hospital Research Ethics Board (File no. 14–340), Western University Health Sciences Research Ethics Board (file no. 105752), Nova Scotia Health Authority Research Ethics Board (file no. 1020827), the Research Ethics Board of Sunnybrook Health Sciences Centre (file no. 042–2015), Hamilton Integrated Research Ethics Board (file no. 14–405), the Mount Sinai Hospital Research Ethics Board (file no. 14–0341-E) and the Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board (file no. 6018723).

    Acknowledgments

    We are grateful to all of the families who participated in this study and took the time to share their insights and experiences with us. The authors also thank Lindsay McKay for her contributions to study development and interviewing, and the Canadian Donation and Transplantation Research Program for the opportunity to share earlier versions of this work at the 2018 annual meeting.

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    Footnotes

    • Contributors AvB, VG, AS, LH, SD and JC contributed to the conception and design of the project. AvB, VG, AS and JC participated in the acquisition and analysis of data for the work; NM, CW, LH and SD additionally contributed to interpretation of data for the work. AvB, NM, CW, VG, AS, LH, SD and JC drafted the work and revised it critically for important intellectual content and gave final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

    • Funding This project was partially funded by the Bertram Loeb Research Chair and by the Canadian Donation and Transplantation Research Program.

    • Competing interests CW receives consulting income from Cardialen, Eli Lilly and Company and Research Triangle Institute (RTI) International. LH is a paid consultant for Canadian Blood Services.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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