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Australasian Human Research Ethics Consultancy Services Pty Ltd (AHRECS)

Embedding clinical research as part of routine healthcare: Managing the potential for competing interests.0

 

Nik Zeps
AHRECS Consultant

 

Clinical trials are widely accepted as the best method for understanding whether any particular medical intervention is safe, efficacious, acceptable to patients and cost-effective. Almost every Health Service in Australia runs clinical trials of one sort or another. Enrolment of patients (in this instance they are all patients and not healthy volunteers) into clinical trials through health services operates as a separate activity to routine health care delivery and is managed through its own governance processes rather than as a part of clinical governance. This is widely recognised to be necessary but is unfortunately inefficient, duplicative in many instances, has a lack of objectivity and as a result of poor resourcing and training, is often slow and regarded as problematic by the research community. Sadly, there is a fairly widespread view amongst researchers that Research Governance is a bureaucratic hurdle rather than a means to ensure their research will be safe, quality work, be well managed and have significant impact.

One of the problems with the current system is that it treats all clinical trials as a single category rather than recognising the profound differences between trials that are seeking to establish new evidence for experimental therapeutics and those that are comparing existing therapeutic interventions (so-called Comparative Effectiveness Trials-CETs). It is clear that the risks of being enrolled in a CET are likely to be less than if being enrolled in a trial involving an unapproved therapeutic. Indeed many patients expect clinicians to deliver evidence based care, rather than practice variation, which can only elicited from high quality CETs  However, it is also true that if a person is randomised into the standard-of-care control arm of a trial of an unapproved therapeutic is at no greater risk than if they were not in the trial. Indeed, there is a broad range of evidence that participation in trials has an overall benefit in terms of safety and outcomes even for the control arms so one could argue that being in trial is by and large better than not being in a trial. It is also widely believed that the act of randomisation, the key feature underlying the power of clinical trials, is in itself risky and lifts any trial into a category that requires careful management. The National Statement does not make any such comment about risk related to randomisation and this view is one of subjective convention rather than one based on any proper assessment of risk.

Another feature of managing clinical trials is ensuring that potential participants are given appropriate information free of any coercion or inducements so that they can make a completely autonomous and sufficiently informed decision to participate or not. To ensure this a great deal of time and attention is paid to reviewing increasingly lengthy and complicated Participant Information Sheets and Consent forms (PICFs). In contrast almost no meaningful time is spent on evaluating the skills of the team in providing the information and being able to answer questions in a manner that ensures there is no coercive or inducive behaviour. Moreover, to my knowledge, no HREC has ever sent observers to audit how a participant is recruited, whether consumer input was sought in the development of the enrolment strategy or to evaluate notes taken as part of the consent process. This would appear to be the more important component of understanding whether the ethical issues arising from enrolling participants in a trial are being met.

Another area of research governance in need of an overhaul is a proper evaluation of the competing interests involved in running clinical trials in the first place. The term ‘conflict of interest’ is problematic in itself because it inherently assumes a negative position rather than recognising that instead there are legitimate instances of competing interests that have to be balanced and that it is not a black and white scenario. The NHMRC National Ethics Conference held in 2005 had this topic as it’s central theme and attendees discussed the need to take a more nuanced approach that included a broader consideration of competing rather than conflicting interests. These competing interests apply to participants themselves, the health professionals running the trials, the institutions responsible for operating the site where the trials are being done and finally the funders of the trials who may also be the ‘sponsor’ in the definition adopted by the TGA, that is, those with a direct vested interest in proving an unapproved therapeutic is better than existing practice so they can market their product for profit. Frameworks for managing these competing interests are often little more than answering ‘conflict of interest’ questions in the ethics application forms or on institutional declaration forms and stating that any institutional policy is being followed. This is clearly inadequate for a variety of reasons. Firstly, in my view after having worked in public and private institutions for 20 years, is that there is a check box mentality to managing potential competing interests with no resources deployed to either teaching staff about it or exploring the more subtle elements as opposed to simply addressing the blatantly obvious ones such as a direct financial conflicts. Secondly,

Given the earlier statements about the potential benefits of being enrolled in trials, and also the fact that for a subset of people the trial may be the only way to access a potentially life-saving treatment, participants themselves may have a profound self interest in participation. At the end of the day who are we doing research for if not the end-users, therefore system generated research barriers inadvertently have a direct impact on patients and members of the public.

It is also possible that participation in the trial leads to funding of components of care that would otherwise be a cost to the person. Some hold the view that people on trials should not experience any out-of-pocket expenses, even where those expenses would occur if they were not on the study. Arguments presented by investigators and sponsors that people should still have to pay any out-of-pocket expenses for standard-of-care components of a trial have been met with opposition by HRECs and institutions in some instances.

Health services are encouraged to run clinical trials for a variety of reasons that include being seen to be a centre of innovation and learning as well as providing access to cutting edge treatments. The reputational benefits are a discrete interest of the organisation that may, if connected to revenue from increased referrals, also be regarded as a potential marketing tool.  In addition, some have argued that government funders or health funds should not have to pay for treatments provided during any part of a clinical trial and therefore enrolment in trials is a means to offset some of the expenses associated with providing care to people in the health service. Some also argue that to promote clinical trial activity health services should have enrolment of patients in trials as a Key Performance Indicator (KPI) despite the obvious issues arising from simply working in ways that focus on meeting this that may not align with the best interests of participants. Indeed, whilst setting KPIs may seem like a good idea they create perverse incentives that are difficult to manage in the existing framework.

A topic that is rarely adequately discussed is the conflicts of interest of the institution that is both the site of the research, enjoying some of financial and reputation benefit from doing so, having a degree of duty of care for the participant, plus conducting the ethical and governance review. Commercially sponsored studies bring in revenue which is used to offset the costs of managing a clinical trial infrastructure. Ironically, making HRECs and Research Governance Offices dependent on revenue from commercial sponsors through fees is a major potential risk for conflicts of interest to arise, particularly where pressure is put to streamline approvals which could compromise more thorough evaluation of risks. Clearly a need to balance efficiency with due process is needed, but the dependence on fees that are not linked in any way to actual work done in terms of proportionate fee structures creates a clear conflict of interest within organisations. There is also a significant issue with using clinical trial revenue from commercially sponsored studies to subsidise the costs of Investigator led studies which do not otherwise enjoy such financial support. Whilst highly attractive to cash-strapped organisation unwilling to invest in such trials, the dependence on such revenue is far from ideal, and in some instances means that these trials cannot be opened as they may compete for recruitment of the same patient population and revenue generating trials will take precedence. I have observed this on several occasions at my own and other institutions, so it is far from a hypothetical risk.

Finally, investigators themselves may have competing interests with respect to enrolling people into trials and there have been arguments against permitting doctors who are both a chief investigator and the primary care provider for a patient from being involved in enrolling a person into a study. This is a fundamentally flawed argument and not one supported in the National Statement. Health Professionals have a primary responsibility to ensure the safety of those in their care and this is enshrined in a legal framework that could result in them losing their status as a health provider for any serious transgressions. Health Professionals should be in true equipoise regarding whether a person participates in a study or not and only suggest it if it would not be against their interests. Those paid to do research (study coordinators and Research Nurses) have competing interests to enrol people with no such equipoise and penalty for failing to exercise good judgement about whether a person should or should not participate. For this reason for medical interventions only doctors should decide whether a person should be invited to participate and should provide independent advice regarding the risks and benefits. Recognising where competing interests to enrol a person exist are managed well on the whole although I have also experienced instances in which obliviousness to the actual conflict of interest of being an investigator and having a financial interest in a product were not identified by doctors as being a direct conflict despite filling in forms that asked them to identify these. Therefore, it is not enough to simply write policies and ask people to fill in forms and appropriate training and the development of a culture that supports people to think about what they are doing is needed.

With our thanks to Nicola Straiton for her helpful comments on an earlier draft.

It is perhaps worthwhile for institutions implementing the Australian Clinical Trial Governance Framework overseen by the Australian Commission for Safety and Quality in Health Care (ACSQHC) to incorporate key parts of managing competing interests used in clinical governance for research activities as these likely overlap. A reasonable question can be asked: Do potential participants appreciate the conflicts of the parties they might assume are supposed to safeguard their welfare and interests? What is therefore needed is more than simply listing financial interests or relationships in ethics and governance applications. Instead a systematic and sophisticated approach is required that weighs up the risks and benefits of running research at a strategic level that is deployed as a core part of the culture of an organisation rather than as check box approach in research applications.
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This post may be cited as:

Zeps, N. (29 June 2020) Embedding clinical research as part of routine healthcare: Managing the potential for competing interests. Research Ethics Monthly. Retrieved from: https://ahrecs.com/human-research-ethics/embedding-clinical-research-as-part-of-routine-healthcare-managing-the-potential-for-competing-interests

A checklist to assist a supervisor to check a candidate’s research ethics review application0

 

“Regulations don’t solve things. Supervision solves things”
Wilbur Ross 2015

Dr Gary Allen, Prof. Colin Thomson AM and Prof Mark Israel
AHRECS Senior Consultants

HDR supervisors should, and often do, play an important role in the formulation of a candidate’s research ethics review application. If you talk to an experienced busy research ethics committee member, they will tell you they’ve seen too many applications where there wasn’t any indication the supervisor even saw the application prior to its submission.

Many institutions consider the supervisor to be the lead investigator for candidate research. Even those that don’t usually will expect the supervisor to be a key adviser and mentor for the candidate’s passage through the research ethics review process.

A supervisor not taking an active role in a candidate’s review application can reflect a worrying attitude: “I don’t have time to know about research ethics in detail. The candidate should submit what they have, the experts on the committee can tell them what they need to fix and how they want it changed.”

Such thinking is irresponsible and concerning at numerous levels, not least because research ethics is a fundamental component of the quality design of research.

Being able to think and write about ethical challenges is an essential component of the research training of new researchers.

A supervisor or a research school that isn’t systematically engaged in a candidate’s ethical capacity-building and professional development is failing them.

But a not unreasonable question is “What should I be looking for, when I read an HDR candidate’s application?” A reader of the Research Ethics Monthly asked for a tool she could use.

Attached here is the start of such a tool. The Research Ethics Monthly community includes some very experienced research ethics reviewers. It would be deeply appreciated if you could comment on what we have drafted and suggest other elements for the tool.

This post may be cited as:
Allen, G., Thomson, C. & Israel, M. (24 May 2020) A checklist to assist supervisor to check a candidate’s research ethics review application Research Ethics Monthly. Retrieved from: https://ahrecs.com/human-research-ethics/a-checklist-to-assist-supervisor-to-check-a-candidates-research-ethics-review-application

Why autism research needs more input from autistic people0

 

Elle Loughran
Student, Trinity College Dublin
Elle Loughran is a Laidlaw scholar studying genetics at Trinity College Dublin in Ireland

This post first appeared in Spectrum, the leading site for autism research news.

I am a student and researcher studying evolutionary genetics, and I am autistic. I often come across papers on autism research, but unfortunately, reading them is rarely a positive experience.

Too much autism research fails to acknowledge autistics as people who can read and make valuable contributions to the field. Instead, it casts them as little more than passive study participants or recipients of treatment. This shortsightedness damages research and scientists’ ability to help autistic people.

Reading autism research as an autistic person can feel like being treated as an alien. For example, consider a 2019 paper that stated: “This finding reinforces other work which shows that autistic people can have, maintain, and value close romantic relationships and friendships.” Imagine how bizarre it would be to read that about yourself.

I do not mean to pick on that paper in particular, but on a research culture in which anyone would think that sort of statement needs to be made.

This sort of culture results in seeing top researchers throw around blatantly wrong and offensive ideas about my community. For an old but powerful example, British researcher Simon Baron-Cohen endorsed a quote that suggested autistic individuals experience people at dinner parties as “noisy skin bags” that are “draped over chairs.” In my view, the appropriate response to that is, “No, that is absolutely not how we experience anything. What the hell?” Of course, that would not be an appropriate academic reply.

I understand that even seemingly obvious things need to be examined and tested in science, but if someone were to suggest that the moon is made of cheese, I doubt researchers would insist on disproving it with a study. Yet somehow autistic people must be so strange and unknowable to researchers that they cannot dismiss equally implausible characterizations of us.

In fact, many autistic people are available to answer questions about how we see things. Many of us speak up and share our stories proactively. It can seem to us as if scientists are not listening.

Then there are papers that suggest society would rather fewer people like me existed — and not because they care about my suffering. Or those that survey the prospects of preventing autism, pointing out that these are “high priorities for researchers, parents, advocates, clinicians, and educators.” Why is there is no mention of autistic people on that list?

Integration barriers:

The opportunities for someone like me to correct the culture in autism research are limited.

Often when I see these things in the course of my work, I just sigh and ignore them. If I’m discussing a paper with my scientific peers, I do not want to bring up issues with the paper’s treatment of autism and be seen as an ideologue, research subject or object of pity rather than as a respected colleague.

Other people’s responses can also thwart meaningful exchange. Last summer, I ‘came out’ as autistic while in conversation with an autism researcher and several of her colleagues. The people in the group responded with something along the lines of,  “Oh, well, you’re not like other autistic people, so those points do not apply to them.”

If a person’s ability to converse with you makes you assume she is not like ‘real autistics,’ then your idea of autism is automatically going to be ‘people who can’t talk to me.’  You will have a flawed understanding of autism and may not be able to see autistic people as potential colleagues. This risks researchers perceiving autistic people purely as research subjects who do not talk back, have opinions or contribute to the process.

Autistic people are treasure troves of information on their own lives. By including more autistic voices in research, we as scientists could improve our ability to gather knowledge about the condition.

Given the flaws in prevailing theories of autistic psychology, I believe we should encourage more qualitative, open-ended research that seeks input from autistic people and establishes a firmer basis for future studies. We could also seek their help in prioritizing treatment targets. Likewise, if biomedical researchers are going to get funding for studying autism, they must make more of an effort to engage with the autistic community and their wishes.

Things are getting better, and many researchers are doing good work. But listening to autistic people could help them make faster progress. Autistic people are not aliens with whom scientists cannot communicate. We are right here. We are reading what you have to say, and that communication can go both ways.

This post may be cited as:

Loughran, E.  (27 April 2020) Why autism research needs more input from autistic people. Research Ethics Monthly. Retrieved from: https://ahrecs.com/human-research-ethics/why-autism-research-needs-more-input-from-autistic-people

COVID 19, human research and human research ethics review1

 

Prof. Colin Thomson AM
AHRECS Senior Consultant

We at AHRECS, like all our friends, colleagues and clients, are becoming more and more aware of the immediate and probably long-lasting impact of this pandemic on almost every part of our lives. It has compelled researchers to vary methodologies adopted for both ongoing and planned human research. It has also been forcing institutions to adapt human research ethics review processes to enable responsible social distancing.

In this brief item, we are opening a conversation to offer assistance, ideas, successes and strategies to achieve these changes while maintaining the ethics and quality of human research and ethics review.
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Human research ethics review

A number of our clients have long been conducting ethics review meetings online because of geographical necessity. Australia’s regional universities have led these innovations and acquired considerable experience in managing to achieve effective, efficient and quality ethics review. They use different online platforms and have experience of the strengths and weaknesses of several of these in running both synchronous meetings and asynchronous review processes.

They also have experience of assisting those committee members who have been reluctant to review digital applications. The current crisis may compel further limitations on such assistance; for instance, institutions may be unable to print and dispatch agenda papers and members may be less willing to receive them. Experience in enabling less IT-savvy members to adopt online processes with comfort could be a value now to other institutions making these changes.

There may also be substantive issues in addition to these ones of process.  For example, how does COVID-19 change our perceptions of merit; what if it shifts the balance in an unfavourable direction after a project has been approved?

We have asked some of our clients who have these experiences to respond to this item and encourage others to either offer or seek assistance, not necessarily through AHRECS, but directly. This may be the time in which the development of broader community of human research ethics review practice will be more needed than ever.
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Human research

For researchers, particularly those with approved projects that involve interaction with participants, the new restrictions on physical distancing and self-isolation are likely to present significant difficulties in continuing and completing their projects. They will need to change the manner of that interaction and the ways they collect the data they need so as to limit risks to participants and to themselves.

In normal circumstances, such changes would require prior ethics approval to conform to the conditions of approval that the National Statement requires (National Statement 5.5.6 (c)). However, the consequences for researchers of seeking prior approval may have a greater impact on the continuity and completion of their work and, in busy research institutions, lead to a significant workload increase in approval requests for urgent project variations.  In addition, those alterations to data collection will involve, in due course, changes in the manner in which data are stored, used and either retained or destroyed, all of which would, in normal circumstances, require consent from participants.

Other issues that researchers may face include:

  1. Identifying and fulfilling the responsibilities that arise when they have to close down their research, e.g. can they use data already collected? Do they inform participants and, if so, how?
  2. What obligations they may have to participants who are distressed by the current situation, especially when relevant to the research, as it is entirely foreseeable?
  3. How do they continue to engage in consultations to which they are committed, whether with communities or with all stakeholders?

In the situation that now presents itself, new strategies will need to be devised and it is likely these will depend more than ever on the ethics reviewers’ trust of researchers. For example, an institution could permit researchers to make urgent changes themselves to data collection methods in order to protect participants and meet COVID-19 limitations on condition that they notify the ethics reviewers as soon as practicable following the implementation of the change. That later application could also include a request for approval of changes to data use, management and retention or destruction.
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Guidance for researchers

Australian governments at Commonwealth, State and Territory level have provided combined guidance for researchers, especially those conducting clinical trials and other institutions have combined to offer practical advice for researchers on how to negotiate needed changes and ethics review.
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Research about COVID-19

The COVID-19 situation will generate research initiatives, not only in relation to the immediate medical needs such as vaccines, but also about the impact on health professionals, researchers, and families of those victims of infection, serious illness or death, as well as about the social impact of information, social distancing and self-isolation.

In vaccine projects, issues of justice in inclusion of participants are likely to be difficult to resolve: should all be included or only those capable of a voluntary consent.  And achieving an ethically sound consent will be complicated by the need to provide sufficient information, counter the possibility of social pressure to participate or the heightened influence of health professionals.  As Haaser says, “It is not easy to say no to a hero.”
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An invitation

In this brief note, these are but early suggestions. We invite our readers to respond to these thoughts with ideas and experience of strategies that they, as researchers or ethics reviewers, have adopted to address the new needs.

Further, and more importantly, this invitation is to encourage institutions, ethics review administrators, ethics review committees and researchers to exchange their ideas and their experiences.  It may be ironic that one of the effects of the COVID-19 crisis is to promote a wider community of good ethical human research practice – but it would nonetheless be a very good outcome.

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This post may be cited as:
Thomson, C. (18 April 2020) COVID 19, human research and human research ethics review Research Ethics Monthly. Retrieved from: https://ahrecs.com/human-research-ethics/covid-19-human-research-and-human-research-ethics-review

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