Patients In Research: What Patients Should Require
By James Coyne
In this edition of Mind the Brain, I suggest how patients, individually and collectively, can take responsibility for advancing this important initiative themselves.
NoteStreams are readable online but they’re even better in the free App!
The NoteStream™ app is for learning about things that interest you: from music to history, to classic literature or cocktails. NoteStreams are truly easy to read on your smartphone—so you can learn more about the world around you and start a fresh conversation.
For a list of all authors on NoteStream, click here.
Read the NoteStream below, or download the app and read it on the go!
Patients Involvement In Research
A bold BMJ editorial calls for more patient involvement in the design, implementation, and interpretation of research – but ends on a sobering note: The BMJ has so little such involvement to report.
In this edition of Mind the Brain, I suggest how patients, individually and collectively, can take responsibility for advancing this important initiative themselves.
I write in a context defined by recent events.
• Government-funded researchers offered inaccurate interpretations of their results [1, 2].
• An unprecedented number of patients have judged the researchers’ interpretation of their results as harmful to their well-being.
• The researchers then violated government-supported data sharing policies in refusing to release their data for independent analysis.
• Patients were vilified in the investigators’ efforts to justify their refusal to release the data.
Things To Consider
These events underscore the need for patients to require certain documentation before deciding whether to participate in research.
Declining to participate in clinical research is a patient’s inalienable right that must not jeopardize the receipt of routine treatment or lead to retaliation.
A simple step: in deciding whether to participate in research, patients can insist that any consent form they sign contains documentation of patient involvement at all phases of the research. If there is no detailing of how patients were involved in the design of this study and how they will be involved in the interpretation, patients should consider not consenting.
Exercise Your Rights
Similarly, patients should consider refusing to sign consent forms that do not expressly indicate that the data will be readily available for further analyses, preferably by placing the data in a publicly accessible depository.
Patients exercising their rights in these ways will make for better and more useful biomedical research, as well as research that is more patient-oriented
The BMJ Editorial
The editorial Research Is the Future, Get Involved declares:
More than three million NHS patients took part in research over the past five years. Bravo. Now let’s make sure that patients are properly involved, not just as participants but in trial conception, design, and conduct and the analysis, reporting, and dissemination of results.
But in the next sentences, the editorial describes how The BMJ’s laudable efforts to get researchers to demonstrate how patients were involved have not produced impressive results:
You may have noticed the new “patient involvement” box in The BMJ’s research articles. Sadly, all too often the text reads something like, “No patients were involved in setting the research question or the outcome measures; nor were they involved in the design and implementation of the study.
There are no plans to involve patients in the dissemination of results.
We hope that the shock of such statements will stimulate change. Examples of good patient involvement will also help: see the multicentre randomised trial on stepped care for depression and anxiety.
Our plan is to shine a light on the current state of affairs and then gradually raise the bar. Working with other journals, research funders, and ethics committees, we hope that at some time in the future only research in which patients have been fully involved will be considered acceptable.
Setting A Research Agenda
In their instructions to authors, The BMJ includes a section Reporting patients’ involvement in research which states:
As part of its patient partnership strategy, The BMJ is encouraging active patient involvement in setting the research agenda.
We appreciate that not all authors of research papers will have done this, and we will still consider your paper if you did not involve patients at an early stage. We do, however, request that all authors provide a statement in the methods section under the subheading Patient involvement.
This should provide a brief response to the following questions:
How was the development of the research question and outcome measures informed by patients’ priorities, experience, and preferences? How did you involve patients in the design of this study?
Patients Involvement With The Results
Recent events suggest that these instructions should be amended with the following question:
How were patients involved in the interpretation of results?
The instructions to authors should also elaborate that the intent is require description of how results were shared with patients before publication and dissemination to the news media. This process should be interactive with the possibility of corrective feedback, rather than a simple presentation of the results to the patients without opportunity for comment or for suggesting qualification of the interpretations that will be made. This process should be described in the article.
A Patient Partnership
Material offered by The BMJ in support of their initiative include an editorial, Patient Partnership, which explains:
The strategy brings landmark changes to The BMJ’sinternal processes, and seeks to place the journal at the forefront of the international debate on the science, art, and implementation of meaningful, productive partnership with patients. It was “co –produced” with the members of our new international patient advisory panel, which was set up in January 2014. It’s members continue to inform our thinking and help us with implementation of our strategy.
The “Patients Included” Certificate
For its efforts, The BMJ has been the first medical journal to receive the “Patients Included” Certificate from Lucien Engelen’s Radboud REshape Academy.
For his part, Lucien had previously announced:
“I will ‘NO-SHOW’ at healthcare conferences that do not add patients TO or IN their programme or invite them to be IN the audience. Also I will no longer give lectures/keynotes at ‘NO-SHOW’ conferences.”
But strong words need an action plan to become more than mere words. Although laudable exceptions can be noted, they are few and far between.
Which Way To Go
In Beyond rhetoric: we need a strategy for patient involvement in the health service, NHS user Sarah Thornton has called the UK government to task for being heavy on the hyperbole of empowering patients but lacking a robust strategy for implementing it.
The same could be said for the floundering effort of The BMJ to support patient empowerment in research.
So, should patients just remain patient, keep signing up for clinical trials and hope that funders eventually get more patient oriented in the decisions about grants and that researchers eventually become more patient-oriented?
Recent events suggest that is unwise.
Refusing To Share The Data
The BMJ patient-oriented initiative versus the PACE investigators’ refusal to share data and the vilification of patients who object to their interpretation of the data.
As previously detailed here the PACE investigators have steadfastly refused to provide the data for independent evaluation of claims. In doing so, they are defying numerous published standards from governmental and funding agencies that dictate sharing of data. Ironically, in justifying this refusal, the investigators cite possible repercussions of releasing the data for the ability to conduct future research.
Refusing PACE’s Argument
Fortunately, in a decision against the PACE investigators, the UK Information Commissioner’s Office (ICO) rejected this argument because:
He is also not convinced that there is sufficient evidence for him to determine that disclosure would be likely to deter significant numbers of other potential participants from volunteering to take part in future studies so as to affect the University’s ability to undertake such research. As a result, the Commissioner is reluctant to accept that disclosure of the withheld information would be likely to have an adverse effect on the University’s future ability to attract necessary funding and to carry out research in this area, with a consequent effect on its reputation and ability to recruit staff and students.
Further Problems With PACE
But the PACE investigators have appealed this decision and continue to withhold their data.
Moreover in their initial refusal to share the data, they characterized patients who objected to the possible harm of their interpretations as a small vocal minority.
“The PACE trial has been subject to extreme scrutiny and opponents have been against it for several years. There has been a concerted effort by a vocal minority whose views as to the causes and treatment of CFS/ME do not comport with the PACE trial and who, it is QMUL’s belief, are trying to discredit the trial.
Indeed, as noted by the editor of the Lancet, after the 2011 paper’s publication, the nature of this comprised not a ‘scientific debate’ but an “orchestrated response trying to undermine the credibility of the study from patient groups [and]… also the credibility of the investigators and that’s what I think is one of the other alarming aspects of this.
This isn’t a purely scientific debate; this is going to the heart of the integrity of the scientists who conducted this study.”
Several Claims Later
Physician Charles Shepherd, himself a sufferer of myalgic encephalomyelitis (ME) notes:
• Over 10,000 people signed a petition calling for claims of the PACE investigators relating to so-called recovery to be retracted.
• In a survey of 1,428 people with ME, 73 per cent reported that CBT had no effect on symptoms while 74 per cent reported that GET had made their condition worse.
The BMJ’s Position On Data Sharing
A May 15, 2015 editorial spelled out a new policy at The BMJ concerning data sharing, The BMJ requires data sharing on request for all trials:
Heeding calls from the Institute of Medicine, WHO, and the Nordic Trial Alliance, we are extending our policy...
The movement to make data from clinical trials widely accessible has achieved enormous success, and it is now time for medical journals to play their part. From 1 July The BMJ will extend its requirements for data sharing to apply to all submitted clinical trials, not just those that test drugs or devices. The data transparency revolution is gathering pace.2 Last month, the World Health Organization (WHO) and the Nordic Trial Alliance released important declarations about clinical trial transparency.
PLoS Journals’ Policy On Data Sharing
On December 12, 2013, the PLOS journals scooped other major publishers with:
PLOS journals require authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception.
When submitting a manuscript online, authors must provide aData Availability Statement describing compliance with PLOS’s policy. The data availability statement will be published with the article if accepted.
Refusal to share data and related metadata and methods in accordance with this policy will be grounds for rejection. PLOS journal editors encourage researchers to contact them if they encounter difficulties in obtaining data from articles published in PLOS journals.
If restrictions on access to data come to light after publication, we reserve the right to post a correction, to contact the authors’ institutions and funders, or in extreme cases to retract the publication.
This requirement took effect on March 1, 2014. However, one of the most stringent of data sharing policies in the industry was already in effect.
Publication is conditional upon the agreement of the authors to make freely available any materials and information described in their publication that may be reasonably requested by others for the purpose of academic, non-commercial research.
Even the earlier requirement for publication in PLOS journals would have forestalled the delays, struggles, and complicated quasi-legal maneuvering to characterized the PACE investigators’ refusing to release their data.
Behind It All
Patients are not obligated to participate in research, but should freely choose whether to participate based on a weighing of the benefits and risk. Consent to treatment in clinical research needs to be voluntary and fully informed.
Medically ill patients often cannot expect direct personal benefit from participating in a research trial. This is particularly true when trials involve comparison of a treatment that they want that is not otherwise available, but they risk getting randomized to a poorly defined and inadequate routine care.
No Direct Benefit
Their needs continue to be neglected, but now burdened by multiple and sometimes intrusive assessments.
This is also the case with descriptive observational research and particularly phase 1 clinical studies that provide no direct benefit to participating patients, only the prospect of improving the care of future patients.
In recognition that many research projects do not directly benefit individual patients, consent forms identify possible benefits to other current and future patients and to society at large.
The World Medical Association (WMA) Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects spells out a set of principles protecting the rights of human subjects, it includes:
In medical research involving human subjects capable of giving informed consent, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail, post-study provisions and any other relevant aspects of the study.
Right To Refuse Or Withdraw
The potential subject must be informed of the right to refuse to participate in the study or to withdraw consent to participate at any time without reprisal.
Special attention should be given to the specific information needs of individual potential subjects as well as to the methods used to deliver the information.
Can patients pick up the challenge of realizing the promise of The BMJ editorial, Research Is the Future, Get Involved ?
One patient to whom I showed an earlier draft objected that this is just another burden being thrust on medical patients who already have their condition and difficult treatment decisions with which to contend.
In Need Of Support
She pointed out so often patient empowerment strategies ended up leaving patients with responsibilities they could not shoulder and that the medical system should have met for them.
I agree that not every patient can take up this burden of promoting both more patient involvement in research and data sharing, but groups of patients can. And when individual patients are willing to take on the sacrifice of insisting on these conditions for their consent, they should be recognized and supported by others.
This is not a matter for patients with particular illnesses or members of patient organizations organized around a particular illness. Rather, this is a contribution to the well-being of society should be applauded and supported across the artificial boundaries drawn around particular conditions or race or
A Powerful Effect
The mere possibility that patients are going to refuse to participate in research that does not have plans for patient involvement or data sharing can have a powerful effect.
It is difficult enough for researchers to accrue sufficient numbers of patients for their studies. If the threat is that they will run into problems because they don’t adequately involve patients, they will be proactive in redesigning the research strategies and reflecting it in their consent forms, if they are serious about getting their research done.
A Better Approach
Patients are looking after the broader society in participating in medical research.
However, if researchers do not take steps to ensure that society gets the greatest possible benefit, patients can just say no, we won’t consent to participation.
Acknowledgments: I benefited from discussions with numerous patients and some professionals in writing and revising this blog. Because some of the patients desired anonymity, I will simply give credit to the group. However, I am responsible for any excesses or inaccuracies that may have escaped their scrutiny.