Introduction

Since the 1980s demand for tissue for research has grown dramatically [1], and this demand is expected to continue as genomic, post genomic and precision medicine research activities expand [2]. Demand for health data is also increasing to fuel research in artificial intelligence, big data analytics and learning health care systems (which support the continuous generation of knowledge to inform the provision of care). Data-intensive medical research challenges the traditional 'consent or anonymise approach' approach to ethical data regulation [3]. Health and genomic data are now being shared, re-used, linked and analysed on an unprecedented scale, often outside the parameters for which the data was originally collected.

Many countries, including New Zealand, have set national strategic priorities to build a knowledge economy, and to intentionally harness data-driven technologies, science and innovation to drive economic growth [4]. Clinicians are encouraged to support medical research by generating research questions, facilitating consent in the clinic for the future use of biological specimens and data for research, and supporting research translation back into the clinic [5, 6]. This may lead to relatively inexperienced clinician-researchers proposing to undertake research with data or samples they encounter in their clinical roles.

However, the regulatory structure for secondary use of health information and tissue is complex and difficult to navigate, even for experienced health researchers. Such research may fall under multiple regulatory instruments including legislation, regulation or policy relating to privacy, data protection, human tissue use and human subjects’ research. This regulatory ecosystem aims to support socially valuable health research and innovation, while protecting privacy and public trust [7]. The evolving and increasingly interconnected nature of scientific research points to a complex web of relationships requiring trust, stewardship and responsible governance [8]. Hoeyer asks “what can be done to make biobanks into trustworthy institutions of long-term social durability?”[9] This is a complicated balance that requires the regulatory system to simultaneously:

1. protect the existing public trust in health and research institutions;
2. establish a social and cultural licence for the sharing of tissue and data for research;
3. facilitate access to research material (tissue and data);
4. protect patients’ privacy and other legal rights; and
5. prevent or minimise harm arising from data and tissue misuse or poorly designed or communicated research.

Research Ethics Committees (RECs) and Institutional Review Boards (IRBs) have an important role in this regulatory process. Many jurisdictions and international guidance documents allow an IRB/REC to waive the consent requirement for secondary use research, in cases where gaining consent would be impractical or would impede the scientific validity of the study; where the study addresses important health questions; and poses minimal risk of harm to data subjects [10–13]. Guidelines typically require that all three criteria are satisfied in order to grant a consent waiver. The new EU General Data Protection Regulation gives member states freedom in determining whether patient consent is necessary for secondary use of health data for medical research [14]. If RECs/IRBs decline to grant a waiver of consent, researchers must abandon the research or re-consent all patients and participants whose tissue or data is included in the dataset. Previous research has shown RECs feel a heavy burden of responsibility to protect patients’ and publics’ interests when patient consent is not sought [15, 16].

Regulation of health data is broadly considered by researchers to be a barrier to conducting health research [15, 17]. Even in the context of more traditional clinical research, RECs come under criticism from researchers on the grounds that they are secretive [18, 19], inconsistent [20, 21], slow [22], and the ethics review process is unduly burdensome [23, 24]. There is a recently emerging literature on how RECs function and make decisions [15, 25–30]. Our research adds to this growing literature and is particularly interesting because it compares the opinions of researchers and RECs, illuminating different perspectives on the review process, styles of ethical reasoning and issues of concern in relation to secondary research. In highlighting these different approaches to ethical reasoning, we hope to provide a constructive platform for greater understanding between researches and RECs.

In this paper we provide a comprehensive picture of the points of contention between New Zealand researchers, RECs and other stakeholders regarding secondary use research. We report on qualitative research involving all four national-level RECs in New Zealand (called Health and Disability Ethics Committees or HDECs), interviews with researchers and supplementary interviews with surgeons and pathologists. In this paper we focus on philosophical and to some extent legal understandings of consent for research; but we note that consent is sociologically constructed and that our framing only sheds light on some aspects of the consent process [31]. This research focuses on comparing the perspectives of REC members, researchers and other professionals We do not directly investigate patients’ or research participants’ views; and we acknowledge that consent, while a primary focus of this paper, is alone an inadequate solution to participants’ concerns about the use of tissue and data in secondary research [9, 32].

In New Zealand, the National Ethics Advisory Committee–Kāhui Matatika o te Motu (NEAC) issues the National Ethical Standards for Health and Disability Research and Quality Improvement (the Standards) in line with its statutory functions as described in the New Zealand Public Health and Disability Act 2000. HDECs check that research protocols meet the ethical standards set out by NEAC and they must act consistently with New Zealand law (including for example the New Zealand Bill of Rights Act 1990, the Health and Disability Commissioner Act 1994, the Human Tissue Act 2008 and the Privacy Act 1993). These requirements likely shape and frame HDEC views about the ethical issues discussed in this research.

Our study is a unique multi-dimensional, in-depth view of the regulation and practice of secondary research with tissue and data in New Zealand. We go beyond the existing critiques of RECs, to demonstrate the different ways researchers and RECs analyse ethical questions about tissue and data research. This study is important because it demonstrates where researchers and RECs are talking past each other.

Methods

This paper draws on data from three related qualitative studies conducted in New Zealand in 2016–2017. The overall aim was to understand different stakeholders’ perspectives on the ethical issues and regulatory processes relating to secondary research with clinical tissue or data in New Zealand. Further details of the methodology (including the research protocols and interview guides) are provided in S1 Appendix.

Study 1: Focus groups and interviews with members of all four New Zealand national-level research ethics committees—HDECs. In addition, we conducted three observational sessions with the HDECs and multiple discussions with the Ministry of Health HDEC Secretariat and the HDEC Chairs. This study used a participatory observation approach (AB was a long-serving member of one of the HDECs) and thematic analysis. The full methodology is described in a previous paper [15]. Here we present results that were not included in the initial publication. HDEC Chairs have provided feedback and contributed to data interpretation for this manuscript. This study was approved by the Human Health Ethics Committee at the University of Otago H16/090.

Study 2: Semi-structured interviews with thirteen researchers who had applied for approval for a consent waiver for secondary research through the national HDECs process. Participants included both researchers whose applications for consent waivers had been approved and those that had been declined. This study used purposive sampling and thematic analysis. This study was approved by the Human Ethics Committee at the University of Otago 16.028.

Study 3: Semi-structured interviews with five stakeholders (three surgeons and two pathologists). The third study was a small spin-off pilot study that gathered additional data on specific themes emerging from the earlier two studies. This study used purposive sampling and snowballing; and thematic analysis. This study was approved by the Human Health Ethics Committee at the University of Otago H16/034.

Focus groups were conducted in person and interviews were conducted in person or via the phone. Written or oral consent was obtained (and recorded) from all participants. All focus groups and interviews were audio recorded and transcribed by a professional transcriber. Nvivo was used to support data coding and data analysis. All focus groups and interviews were conducted by AB and used semi-structured interview templates, which are attached in the S1 Appendix. AB and AM conducted the coding and data analysis for study 1. AB and AM developed the coding scheme and coded the transcripts for studies 2 and 3. In addition KB and AG read select sections of the transcripts for study 2 and 3 and contributed to data analysis and interpretation.

Transcription and data analysis were conducted iteratively. Saturation was defined as the point at which no new themes were emerging [24]. We reached data saturation for studies 1 and 2 but not for study 3, which was a pilot study and did not aim to reach saturation.

Summary results and draft papers were presented orally and/or in writing to the MOH secretariat and to the Chairs of the HDECs (who had the option of sharing these results with their respective committees). This process helped refine and validate data interpretation. The varied expertise of the research team, combined with the process of stakeholder engagement, provided a depth of perspective to support, challenge and deepen the data analysis and interpretation [33].

Results

The data summarised here are drawn from three complementary sets of interviews and focus groups involving a total of 42 participants.

• #1–4 refer to the four HDEC focus groups, including 22 members (members asked not to be identified as individuals)
• #5 and #6 are follow-up interviews with individual HDEC members
• #7–19 refer to interviews with researchers who had applied to HDECs for a consent waiver to access tissue or clinical data without patient consent
• #20–24 refer to interviews with other relevant stakeholders (surgeons and pathologists)

New Zealand is a small country of 4.8 million people and the professionals we spoke to often had experience in multiple roles—as clinicians, researchers, ethics reviewers, setting up tissue banks, management roles. In general the interviews were broad-ranging and addressed multiple perspectives on the issue of secondary use research. The cohort included researchers and clinicians with experience in both the public and private research sectors.

Here we present the most interesting and important points of contention between RECs, researchers and other stakeholders on ethical issues in secondary research. Due to this focus we do not present on other themes present in the data—for example, there was discussion, in all three participant groups, about the difference (technical, ethical, sociological or cultural) between tissue and data. This is perhaps unsurprising given New Zealand has a research framework called Te Mata Ira which provides culturally informed guidelines for biobanking and genomic research that take account of Māori (the indigenous people of New Zealand) views, concerns and expectations about the sharing and use of tissue and DNA in research [34] However in this paper we focus on points of contention because they demonstrate misalignment between the expectations, values and assumptions of RECs and researchers. Results are arranged under the following themes: consent; balancing the social value of the research with consent requirements; and harm.

While we focus on points of contention in this paper, we also note that approximately half the researchers we interviewed thought the REC review process was overall constructive.

Consent

Some researchers were surprised that they would need ethics approval to access biological samples or data for research.

“A lot of these patients are deceased, so we thought that we could probably just go to the labs, get the tissue, and go with it. But um, what we found out pretty quickly was no, that can’t be done.”

(#9)

Re-consenting patients.

In cases where the HDEC required researchers to re-consent patients, many researchers thought this was unnecessary, prohibitively expensive or caused harm and anxiety to patients. In no case had the REC review process convinced researchers that re-consenting patients was necessary.

“…this is always voluntary research that we do it just in our own time, and so we never have a lot of time to do it, and to feel like you’re you know, [re-consenting patients] really felt so unnecessary… And that was pretty upsetting for me… it put me off wanting to do that sort of depth of research study again, because it just, it felt so unnecessary and so misunderstood from the committee… its’ yeah, an incredibly frustrating process.”

(#14)

“And we actually got to a point where the [REC] gave me provisional approval… but, what we had to do to get to that point of provisional approval, my boss has just said, this is completely impractical and you just can’t do it. But [REC] kept going on about why couldn’t I employ a nurse to get consent. “

(#10)

Researchers were also concerned about the potential for the re-consenting process to cause distress to patients or relatives.

“I felt that it was potentially harmful [distressing] actually… I wasn’t worried about the work entailed for us.”

(#11)

It’s too expensive to re-consent patients.

An important point of contention that emerged between researchers and RECs was the question of whether the cost of re-consenting patients satisfied the criterion of impracticability. Cost was not specifically mentioned in the national NEAC Guidelines for Observational Studies [26] in place at the time of the research (the Guidelines have since been updated) (see Table 1).

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Table 1. NEAC guidelines for observational studies.

https://doi.org/10.1371/journal.pone.0235618.t001

RECs were mainly of a view that cost alone did not satisfy the impracticality condition.

“I think when you start putting cost over people’s rights, you are actually on a slippery slope… So, I wouldn’t necessarily be looking at the cost, that’s not my problem.”

(#1)

“I mean [researchers have] had some doozy excuses over the years, can’t be bothered, it’s too much cost…”

(#4)

More specifically, RECs expressed some concern that researchers relying on cost considerations may not have sufficient resources to adequately perform research.

“[if they]…don’t have the resources to be able to [re-consent]…‥you’d have to question; is that researcher going to be adequately competent to be able to do the study, if they’re not …capable of meeting ethical obligations.”

(#6)

An exception here was REC members who were also researchers. This sub-group were more sympathetic to the cost implications of research.

“If it was a study that was hugely beneficial to society as a whole, and would answer a really important question that you couldn’t answer any other way, I would certainly consider [cost].”

(#5)

Researchers however typically thought that cost was a relevant consideration for assessing impracticality. “…the added costs of that would have been prohibitive. … so in every sense, we couldn’t have done it [if consent was required].” (#18)

“…this was a project without any resource…and it would have required me to go and get consent… We would need additional funding for that.”

(#15)

Original consent.

We heard from RECs that some researchers argued consent for secondary research use of data and samples had been obtained during the standard clinical consent process at the point of collection (either during informed consent for surgery or when a patient enrolled with a health service). Our interviews with researchers confirmed this perspective. RECs expressed skepticism that this would qualify as valid informed consent, even broad consent.

“I mentioned [to the REC] that all patients have signed consent, and that consent form actually says ‘I agree to my tissue being used for future research, provided ethical approval is obtained’. And I quoted that, and I got shot down at the committee, and told that that only applied to audits.”

(#12)

Discussion

Here we focus on three points of ethical contention emerging from the research. We focus on points of contentions because these are primary sources of dissatisfaction and stress for both researchers and REC members and highlighting these issues provides a constructive platform for better mutual understanding and alignment in the future. The exiting literature suggests researchers experience significant dissatisfaction with ethics review and our novel findings help illustrate issues where RECs and researchers seem to be talking past one another. First, there is debate about whether the costs of re-consenting patients should satisfy the ‘impracticality’ requirement. Second, our results suggest that researchers adopt a more consequentialists approach, and will trade off the benefit of the research against the cost of getting consent; whereas RECs are more deontological, and only consider public benefit once it has been established that re-consenting is impractical. Third, our results demonstrate the struggle for epistemic authority between different members of the REC and between researchers and RECs.

Conclusion

Data sharing is an essential driver of learning health systems, artificial intelligence and precision medicine. Internationally RECs provide the core regulatory oversight for sharing clinical data and tissue. Our study is innovative in that it provides a multi-dimensional view of the ethics review process for secondary research. REC processes are notoriously frustrating, and often confusing, for researchers. Our research provides detailed insight into the reasoning of RECs and is an important contribution to transparency in the data ecosystem.

Here we have focused on identifying clash points between researchers, RECs and other stakeholders. Points of contention are important because they demonstrate misalignment between the expectation, values and assumption of RECs and researchers. Our research shows that these clash points are sources of stress, anxiety, and conflict among the parties.

There were three key insights that emerged from the research. First there was disagreement as to the role of ‘cost’ in satisfying the ‘impracticality’ criterion for consent waivers. In general researchers thought that cost was relevant; whereas RECs resisted the influence of cost. Second, we identified a difference in approach to ethical reasoning. Researchers took a more consequentialists approach and RECs adopted a primarily deontological approach. Finally our research demonstrated the struggle for epistemic authority between researchers and RECs; with both asserting their superior positions to represent the interests of patients and populations and to accurately identify the benefits and (especially) the risks of research. For example, most researchers were skeptical that secondary research with already collected tissue and data could harm patients, and they were particularly perplexed by RECs concern about the potential for research to stigmatize data subjects.

We hope these insights may provide a platform for mutual understanding and re-alignment of the perspectives of RECs and researchers. We conclude by offering several suggestions to support re-alignment. System leaders should clarify the role of RECs and IRBs with respect to whether committees are essentially administrative (and therefore may give effect to their ethical perspectives here only insofar as those perspectives express and apply the duly established and applicable policy standards) or have scope for free-form ethical analysis and are able to reject protocols on the grounds of their own ethical judgment [40, 41]. As demand for health data and tissue continues to grow, it may also be worth establishing specialist RECs with expertise in data science and biobanks [55]. Research ethics guidelines need to be regularly updated to address novel research methodologies. Revised NEAC guidelines have been released in New Zealand subsequent to this research and they offer greater clarity on the ethical standards for tissue and data research. It is imperative for regulators to clarify whether resource limitations are sufficient grounds for not re-consenting patients. Inexperienced researchers should receive training and support to help them translate a burgeoning research hypothesis into an ethical, code-consistent, safe research protocol. It would be valuable to provide forums for greater researcher and REC interaction, for example joint-training days when new ethical guidance or policy is released. These semi-formal environments could provide a forum for relationship building between RECs and researchers and joint discussion of emerging research methods and the ethical issues arising.

Supporting information

Acknowledgments

We thank the participants for sharing their time and insight, the Ministry of Health for facilitating the research, Maria Stubbe for her guidance on qualitative methods, and Wendy Rogers for her helpful criticisms.