When ethics committees kill

March 26th, 2011 by Ben Goldacre in regulating research | 41 Comments »

Ben Goldacre, The Guardian, Saturday 26 March 2011

Every now and then, very occasionally, a government will do something awesomely good. The budget contains plans for a new unified Health Research Regulatory Agency to streamline the regulations on clinical trials, and so make them cheaper and easier to run.

It’s motivated, disappointingly, by a desire to make the UK a more attractive location for commercial clinical trials. But this is the first time that a government has shown signs of seriously addressing one the most serious ethical problems in medicine: the harm done to patients by ethics committees and regulators.

At present there is a bizarre paradox in medicine. When there is no evidence on which treatment is best, out of two available options, then you can choose one randomly at will, on a whim, in clinic, and be subject to no special safeguards. If, however, you decide to formally randomise in the same situation, and so generate new knowledge to improve treatments now and in the future, then suddenly a world of administrative obstruction opens up before you.

This is not an abstract problem. Here is one example. For years in A&E, patients with serious head injury were often treated with steroids, in the reasonable belief that this would reduce swelling, and so reduce crushing damage to the brain, inside the fixed-volume box of your skull.

Researchers wanted to randomise unconscious patients to receive steroids, or no steroids, instantly in A&E, to find out which was best. This was called the CRASH trial, and it was a famously hard fought battle with ethics committees, even though both treatments – steroids, or no steroids – were in widespread, routine use. Finally, when approval was granted, it turned out that steroids were killing patients.

Only a trial could give us this information. Head injury is common. Patients died unnecessarily while we waited for this trial to be approved.

But it wasn’t just the delay to getting the trial approved. Many research sites insisted on getting written consent for randomisation from a relative of the unconscious patient, just because it was a trial, even though the treatments were exactly what the patients would have received in normal practice, while unconscious, without a relative’s consent. On average, treatment in these centres was delayed by 1.2 hours.

Does a delay harm patients? Of course. And this week, after a paper in the Lancet, for the first time we have quantitative data showing how patients are harmed by ethics committees’ insistence on these delays.

The CRASH-2 trial showed that giving a drug called tranexamic acid reduces the number of deaths for trauma patients with severe bleeding in A&E. What’s more, as you’d expect – since they’re bleeding to death – the sooner it’s given the better.

A one hour delay while you get consent for an unconscious patient in this situation reduces the number of patients helped by tranexamic acid from 63% to 49%.

This doesn’t just harm those individual patients, although we should be clear: it really harms those patients. More than that, if the benefits of a treatment in the real world are attenuated in a trial, because of a delay introduced by the demands of ethics committees, then the trial gives the wrong answer. We incorrectly conclude that an effective treatment is ineffective, and it is abandoned, when it could have saved lives.

These kinds of outcomes are disastrous. Furthermore, it has taken medical researchers to expose them. As the Lancet authors explain, with no small touch of huff: “the lethal effects we have shown might have been found decades ago had the research ethics community accepted a responsibility to provide robust evidence that its prescriptions are likely to do more good than harm.”

Of course there is a role for ethics committees. Of course we don’t want an army of Dr Mengele’s let loose on patients. Of course there will be disagreement on details. But I simply don’t believe that most patients hearing the stories I’ve just told – replicated around the country – would welcome the acts of the ethics committees. The government’s new announcement this week should hasten change, and if you ever get sick, you might be grateful.

Please send your bad science to ben@badscience.net

The CRASH trial:

This was an extraordinary piece of work. At the end of the trial, where the head injuries were pretty bad (a quarter of the people died), it turned out there were two and a half extra deaths for every one hundred people treated with steroids.

www.ncbi.nlm.nih.gov/pubmed/15936423


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41 Responses



  1. matthew_w100 said,

    March 26, 2011 at 10:31 am

    Fascinating article, as ever. Just a peripheral point – Why is Ben Goldacre allowed to translate “Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.” into “it turned out that steroids were killing patients.” whereas the Daily Mail wouldn’t be? :-)

  2. Dingleford said,

    March 26, 2011 at 10:42 am

    Shame on you. You are conflating the need to regulate research to protect participants from over-enthusiastic or (rarely) downright unethical researchers with the need for a public debate about consent in emergency research. And you are way behind the times calling for changes to research ethics committees. The research you cite was carried out in 2004 – the world of research ethics has transformed since then and it’s time you got yourself up to date. If you had bothered to read the report from the Academy of Medical Sciences which has led to the setting up of the Health Research Regulatory Authority you would have seen that it is highly complimentary of the way the National Research Ethics Service (NRES) has developed in recent years to respond to the needs of researchers. I’m sure Research Ethics Committees would welcome further guidance on consent in emergency research, and NRES has structures that enable this to happen in a timely way. I’ll refer the issue to NRES’ Advisory Panel.

    Conflict of interest: Chair of a Research Ethics Committee

  3. nye said,

    March 26, 2011 at 10:45 am

    Without reading the article itself, I’d say based on the abstract:

    “Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids”

    I’d speculate that the sentence “the cause of the rise in risk of death within 2 weeks is unclear” could be more accurately rendered as “the *direct* cause…”, or “the mechanism…”

  4. Ben Goldacre said,

    March 26, 2011 at 11:42 am

    hi matthew_w100, without access to the paper from here i don’t know where you found that sentence, but the CRASH trial showed that steroids increase death after head injury. it’s possible theyre talking about the mechanism being unknown? the worst you could say of the CRASH finding is that the trial was stopped early, iirc, when it was found that steroids were killing people. depending on circumstances, stopping early can mean you’re less sure if your finding of a difference between two groups was statistical artefact, comparable to complaints about “peeking” (a phenomenon which i’ve written on before).

    “Dingleford”: this is very familiar rhetoric, similar to what we hear over the pharmaceutical industry hiding trial results: “those findings are old, the problems have been fixed now, don’t worry”, except they haven’t.

    i was very clear that there is a role for ethics committees (and that people will differ in their view of what they should do). but the barriers to research presented by regulators and ethics committees continue to delay, obstruct, and prevent important research, which results in serious harm to patients, which needs to be factored in. the problem is that community has shown little sign of recognising that problem, or, as shown in the Lancet paper published this week, described above, setting out to measure it.

    i should lastly say, i do think it’s a bit unimpressive for someone to post something a bit personal and nasty (“shame on you” etc), whilst also declaring, and being, a senior figure in administrative bodies involved in this situation. in all seriousness i think it would be right for you to declare your real name.

  5. jodyaberdein said,

    March 26, 2011 at 12:29 pm

    RE: 2,

    Is not the ‘conflation’ more with regard to the fact that if I actually treat a patient based on no firmer evidence than opinion, then I am regulated by the GMC, my local Trust, my own personal standards, and importantly by shared agreement with the patient. If however I admit outside of the consultation that there is only opinion, and that I am going to formally generate stronger evidence in order to improve the situation, then I am still bounded by the GMC, my local Trust, my personal standards, shared agreement, but now also a committee decision which requires prior written approval.

    Interested readers might wish to peruse the IRAS form and guidance:

    www.myresearchproject.org.uk/

  6. penglish said,

    March 26, 2011 at 12:37 pm

    It’s not just in emergency care that there are issues regarding research ethics approval.

    Despite in theory a single ethics committee being able to sign off a project, it used to be the case – and for all I know it still is (I’d love to hear it’s changed) that many local ethics committees would still insist on approving any research project being undertaken in a trust. This means that for trials where large numbers of patients are required – necessarily requiring a multi-centre trial – the bureaucracy and delays involved in getting a research project off the ground wast vast resources, and risk continuing evidence-free treatments that could be harmful or wasteful of resources; or risk not taking up cost-effective treatments because of a lack of evidence.

    I gather that the NHS is worse than universities in this respect. If you want to interview healthcare workers for a qualitative study the NHS requires prior ethical approval over and above the university’s ethical committee approval, for example.

  7. Ben Goldacre said,

    March 26, 2011 at 12:37 pm

    quite.

    i think one of the most disturbing aspects of this whole process is the reluctance of the ethics committee community to engage seriously with this issue. for example, our anonymous head of a REC above cites the AMS report as if it was favourable about the status quo, when in fact it identifies serious problems, and says (quoted in the Plan For Growth):

    “UK health research activities are being seriously undermined by an overly complex regulatory and governance environment”.
    A new pathway for the regulation and governance of health research, Academy of Medical Sciences, January 2011
    www.acmedsci.ac.uk/index.php?pid=47&prid=88

    i recommend reading the report.

  8. penglish said,

    March 26, 2011 at 12:38 pm

    Another problem with the ethics industry is that it has b become increasingly difficult for e.g. students doing masters degrees to do a research project: there just isn’t time for the bureaucracy to approve the study while they’re still students.

  9. QuietKnoll said,

    March 26, 2011 at 12:45 pm

    As a non clinical but nonetheless interested reader of your blog I welcomed this posting. Whether or not this is an “old problem” that has been successfully remedied I am now aware of yet another “unintended consequence” of “well meaning but confused” initiatives.

    It seems to me that people charged with responsibility (who may as a result find themselves accountable for decisions) will often want to feel protected from adverse comment. Resulting risk aversion can often give rise to the opposite of what was intended. In management terms this has been called “Skilled Incompetence”. (It is of course rampant in many health care systems and reforms).

    It is (and will no doubt continue to be) human nature to adopt defensive positions when balancing risk. This is why it is important that “skilled incompetence” in the world of health research and ethics continues to be highlighted.

    So please keep it up – even if at present there appears to be (perhaps temporary) improvement in the processes you have described.

  10. sciencerocks said,

    March 26, 2011 at 1:02 pm

    I do pretty boring, low risk research. I continue to be amazed at the pedantry and the inconsequential issues fussed about by NHS Res Ethics Comm leading to staggering delays. The current system is killing the clinical aspects of the research conducted by my colleagues and I. For example, last year, it took *6 months* to get approval from REC to do a incredibly low-risk, benign study based on results of a test that patients have anyway (we needed to do the test at a follow-up appt where it isn’t usually done). I cannot stress how quick, benign and low risk this was.

    I too agree we need robust ethical oversight. But it has to be *focussed*, *proportionate* and *HELD TO ACCOUNT* for delays and stupid decisions (e.g. delaying for the sake of grammatical pedantry).

    Another reason we need appropriate ethics. I am aware of some researchers who are bypassing the ethics process completely by selling the research as a service evaluation or audit, then writing it up as research. Why? Because the REC process is unwieldy and disproportionate and is preventing good research. I’m not arguing that bypassing it with lame attempts to make research sound like something else is appropriate or acceptable. But it’s happening.

    Finally, I am not convinced that the ComDems motivation for this is about facilitating science and improving patient care. I’m guessing it’s about money changing hands.

  11. Lynch Mason said,

    March 26, 2011 at 1:15 pm

    Those ‘medics’ that present well put together and informative applications do not get delayed. Ethics committees are there to protect jo public, innocent in these events and very vulnerable to medical arrogance which is still unfortunately common. So instead of slamming these committees as incompetent you should a) be on a committee and/or b) understand the issues from all sides and not just the powerful medical lobby. Your article just confirmed my fears that the medical lobby is still all powerful and controlling. I sit on a committee (volunteer expert member) and had a meeting yesterday. All applications were given approval. All researchers came and discussed their applications and it was informative and useful. No delay but safer research volunteers. So get over it we need to protect the subjects.Come up with a better idea.

  12. Ben Goldacre said,

    March 26, 2011 at 1:21 pm

    I am sad to see the ad hominem about “arrogant medics” etc, I’m afraid I don’t regard this as a class war issue.

    I am sadder still that none of the defenders of the status quo have produced a strong justification for the problems I set out, of barriers to research where patients are randomised to treatments that they would receive anyway. The AcadMedSci set out the risks posed by these obstructions.

    “Lynch Mason”, mercifully the government has seen the need for reform, and the “better idea” is being planned and implemented. I hope it works out well. Nobody thinks ethics committees are a bad idea, but there are serious problems around whether their work is, as above, proportionate and focused.

  13. Ant said,

    March 26, 2011 at 2:18 pm

    As a newly qualified junior, I agree with the point around getting approval within the time frame of a degree/rotation. It makes it much easier to get an audit running rather than research and tick the boxes needed for career progression than it is to get involved in anything bigger or more interesting.

    Ultimately, patients are better protected by focused and detailed examination of difficult cases and transparency than they are by a paralyzed indecision. If researchers stop believing that a regulated UK system can produce the data they need, they will go elsewhere, which is good for no-one.

  14. chris lawson said,

    March 26, 2011 at 2:43 pm

    I recall a story from a year or two ago about a new hand hygiene technique that had been shown to reduce in-hospital infections, but which was forcibly ended because the original study had not had ethics committee approval in the EU. I cannot find any details and I’m flying on very vague memories here. Can anyone else remember more?

  15. jodyaberdein said,

    March 26, 2011 at 5:19 pm

    Are you by chance recalling the use of checklists in ITU to reduce catheter associated blood stream infections?

    Paywalled here:

    journals.lww.com/ccmjournal/Abstract/2009/02000/Critical_care_checklists,_the_Keystone_Project,.44.aspx

    But available if you google scholar the title.

    Commentary here:

    www.nejm.org/doi/pdf/10.1056/NEJMp0800372

  16. adzcliff said,

    March 26, 2011 at 5:23 pm

    Penglish.

    Absolutely! The prospect of having to go through the NHS Ethics process for my own (qualitative) MSc research project, was enough to put me off interviewing a handful of NHS staff. It would have been impossible in the time-frame allocated. I ended up using private health providers – which was fine – but my employing Trust may have stood to benefit from my findings and recommendations?

    Anyway…

    Adzcliff

  17. matthew_w100 said,

    March 26, 2011 at 5:37 pm

    Hi Ben,

    Ref your comment #4, that quote was the (whole of) the “Interpretation” section of the abstract of the CRASH paper you linked to…

    If the authors of the paper thought the cause of increased death rate was “unclear”, so should commentators!

    Matthew

  18. Dingleford said,

    March 26, 2011 at 6:00 pm

    Lots to respond to:
    1. Re issue of nicknames. My response was my personal view, I am not representing NRES and there is nothing sinister about my use of a nickname. When I registered on the site it asked for a nickname so I gave the one I use for tripadvisor etc. If you don’t want people to use nicknames, why do you ask for them? I am not a senior administrative person. I included the fact that I am a REC Chair to help readers put my comments in context (which they have). I note that there is a mix of people giving their names or using nicknames.

    2. Ben, I didn’t think “shame on you” was personal and nasty, but clearly you saw it that way and so I apologise if I hurt your feelings.

    3. Anyone sitting on a REC will tell you NRES is never satisfied with the status quo, that is why RECs have transformed over recent years and why the AMC report was generally complimentary about NRES. I agree that overall it was critical of the regulatory environment, which also includes a host of other regulatory agencies and processes. But your piece was aimed solely at RECs, so not very fair. I totally disagree that the research ethics community doesn’t want to engage on these issues.

    4. Proportionate review of low risk studies is something that I know NRES has been addressing, including piloting of proportionate review to get these studies through the system more quickly. But I agree that it still isn’t satisfactory and much more needs to be done to facilitate these studies and student research (while still providing an appropriate degree of protection to participants and researchers).

    5. I agree that emergency research poses complex ethical issues and I know that the research ethics community has been discussing these. The role of RECs is not just to protect research participants and researchers (yes, sometimes they need protecting from themselves), but also to facilitate good research. I think this is an area that RECs can improve on, but sometimes decisions can be difficult and no-one is infallible. As I said before, there needs to be more public debate about consent and those situations where it might be inappropriate to require consent prior to enrolment in trials.

    6. Unfortunately it is not just the likes of Mengele that prospective research participants need protection from, there are plenty of well-meaning or misguided researchers who sometimes fail to recognise the ethical issues in their research. I don’t suppose there was any malevolence intended by the researchers in the Tuskegee study where patients with syphilis were not told of their diagnosis or treated, even when treatment became available.

  19. sciencerocks said,

    March 26, 2011 at 6:14 pm

    @LynchMason

    Me no medic. Me do incredibly low risk, benign research that has to go through our ethics committee at the university. Me get delayed by 6 months or more by ethics committees, and a process, more interested in pedantry and inconsequential issues than facilitating research in a timely manner. Me concerned that some researchers are so frustrated they are doing research without ethics approval at all. Me thinks ethics committee should be held to account (almost impossible at the moment). Me don’t trust ComDems to be motivated for the ‘right’ reasons.

    No longer @LynchMason
    I wish people wouldn’t turn this into a binary issue. (ethics process vs. no ethics process). I don’t think Ben, me or anyone else are arguing for ethics processes to be abandoned. It’s just that the current process lacks focus and is often disproportionate (leading to delays in getting approval and taking action) and is not adequately held to account. As Ben says, it’s almost as our ethical principles suddenly have to change as soon as someone even whispers the word ‘research’.

    In fairness to REC, it was even worse a few years ago. It still sucks though.

  20. sciencerocks said,

    March 26, 2011 at 6:22 pm

    @Dingleford

    Thanks for accepting that more needs to be done to facilitate low risk stuff. Alas NRES don’t really seem to be in any rush to sort this out – its been a problem for years. In the meantime, straight-forward, benign research is being squeezed out of practicality. Something needs to be done urgently. Alas, I don’t feel able to have faith that politicians especially the ConDems will do anything remotely sensible. I do though think there are a lot of excellent people working in research ethics committee who can make this work – although I realise they have challenges in making it happen. I’m lobbying for action more quickly than it takes to turn around an incredibly low risk ethics application! :)

  21. ShadesOfGrey said,

    March 27, 2011 at 12:57 pm

    Everyone is concentrating on Research Governance bureaucracy but a far more dangerous threat is emerging to ALL clinical research in NHS institutions – accountancy.
    I work at the sharp end with a medium London hospital which for 10 years has required all researchers to jump through the following hoops.
    -Must negotiate with 3 support departments on how R&D money will be split between them within the amount available (impossible)
    -Then must get sign off on the proposal from the finance department, the divisional general manager and the divisional clinical director (impossible)
    -Then must set up tracking system to allow payments to be properly made (impossible)

    Combined with a small and deadbeat R&D department the inevitable result is that outside a couple of areas where they previously had big research programmes they have absoloutely no research whatsoever. However they have achieved their stated aim of being certain that they are not losing money by being host to research projects.

    This trust is now being viewed as an exemplar by neighbouring trusts with jaw-dropping financial crises.

    The future is still bleak for research in the UK.

  22. chris lawson said,

    March 27, 2011 at 1:48 pm

    jodayaberdeen,

    Thank you for the references. I don’t think this was the specific case I had in mind — but given my hazy memory it may be — and anyway, even if it is another example, at least I now have a referenced source. My gratitude is boundless!*

    *offer limited to expressions of gratitude only

  23. chris lawson said,

    March 27, 2011 at 2:14 pm

    Matthew@#17,

    The CRASH study showed that being in the corticosteroid arm gave subjects an 18% higher chance of dying than being in the placebo arm and that this was highly statistically significant (p=0.0001). If you prefer absolute risk to relative risk, as all good epidemiologists should, then 18% of subjects on placebo died within 2 weeks of serious head injury, and 21% of those in the treatment arm died (i.e. an extra 3% died *because* they were in the treatment arm). As this was an intervention trial, this means that methylprednisone caused an increase in mortality (and I think 3% is a pretty big risk when you’re talking mortality).

    When the authors say that methylprednisone did not reduce mortality, they are being deliberately restrained in their language. They acknowledge in the paper (including the abstract) that methylprednisone was causing deaths — that’s why they stopped recruiting subjects for the trial. When the authors say the cause is unclear, they are not casting doubt on the findings; they mean that the physical mechanism by which corticosteroids caused the harm is not known.

  24. AdamJacobs said,

    March 27, 2011 at 3:57 pm

    OK, conflict of interest declaration first of all: I’m a member of a REC. That said, I’ve not been afraid to criticise NRES in the past when I think they’re doing something silly. Here’s an example: dianthus.co.uk/mission-impenetrable

    There are some good points made here on both sides. Yes, ethics review can be over-bureaucratic and silly at times. That’s not, as far as I’m aware, NRES policy. I see it as a training issue: not all RECs are up to the standards of the best. A good REC will not delay things unnecessarily for daft reasons, but I accept that not all RECs are good.

    However, I have to say that in my experience, most of the time the researchers have only themselves to blame for delays, because they don’t take the trouble to fill in the application form properly. The form may seem long and bureaucratic, but the questions are there for a reason, that reason being that the ethics committees need to know about these things if they are to make a judgement about whether the research is ethical. Not all questions require lengthy answers (in fact most don’t). But they do need to be answered according to the instructions. Researchers also need to realise that RECs have lay members as well as expert members, so when it says “Make sure this is comprehensible to a lay member: do not simply copy and past the protocol”, it means it. If I had a pound for every application I’d read that simply copied and pasted the protocol into that section, I’d be a rich man.

    Filling in the form is not difficult, and plenty of guidance is available if researchers struggle with it. But some researchers seem to think it’s not an appropriate use of their time to fill in the form, so they do it in a cavalier and slapdash manner (or delegate it to one of their juniors without ever bothering to read it themselves). How can they expect the ethics committee to approve the research in a timely manner if the ethics committee doesn’t have a clue what research is being proposed because the application makes no sense? And I don’t think it’s totally unreasonable that RECs may wonder whether someone who takes such a careless attitude to their work should really be allowed to experiment on human beings.

    Dingleford makes some good points above, but No 6 is particularly pertinent. There are many ways in which research can be unethical, not all of which will always be apparent to researchers. That’s what RECs are for, and their role in doing that needs to be appreciated.

  25. geodoc said,

    March 27, 2011 at 8:50 pm

    Hey, what’s going on here?

    It’s like someone has replaced the real Ben Goldacre with some subtly Daily Mail-esque inversion of the real thing. Don’t disagree with the main thrust of the article (who wouldn’t want to get rid of unnecessarily obstructive red tape?), but:

    Attention grabbing and provocative headline; small selection of extreme and non-representative examples used to generalise wildly (let’s face it, the CRASH trials were an incredible achievement but pretty unusual in terms of setting, challenges with randomisation etc); confusing conflation of two distinct, albeit related, issues (ethics committees approving trials vs time-to-consent within trials); and even some circular/post hoc reasoning (there’s lots of other undiscovered knowledge out there that could ‘save countless lives’ if the research could be done sooner— but the point is, we don’t know what it is because the research hasn’t been done yet*)

    Anyways, thought-provoking as always, but please Ben, don’t stray too far into polemic. My limited encounters with ethics committees haven’t been particularly positive (one annoying delay, one project re-scoped to avoid potential hassle), and this issue is not something I’ve looked at closely- but I doubt it’s as clear cut as you suggest here.

    *this argument amounts to ‘we must do all research faster’, which admittedly is not a bad idea

  26. chris lawson said,

    March 28, 2011 at 7:37 am

    geodoc,

    I’m not sure why you think Ben Goldacre has oversimplified. In this instance there was an observable increase in deaths because of the way ethics approval was handled. The matter is well documented and argued in the paper he referred to. While Ben did not mention it, the paper itself also makes a very cogent point that the way ethics committees operate, clinicians can prescribe medications and perform procedures without approval, but as soon as they try to measure the outcomes of their procedures they face a significant bureaucratic hurdle. Ben did not say that ethics committees were a waste of time, or that they need to be disempowered. He was asking for a more efficient, more predictable, and above all less capricious system.

    It strikes me as odd that in a case where the prevailing ethics approval system has been shown to have resulted in deaths, a number of people rushed to defend ethics committees against an accusation that was never made.

    With regard to Adam Jacobs’ comment — if the process is as easy as you say it is, why is it that so many applications get it wrong? I suspect that the form is far more difficult than you think — perhaps your work on an REC has made you familiar with the forms and the common errors in applications, but to a researcher it may seem incredibly complex. I have face the same problem as a clinician in trying to answer forms for insurance companies. They are not trying to be difficult, but often the way they phrase questions makes it impossible to give a good answer. “When will the patient be able to work at full capacity?” is easy to answer for a straightforward injury like a broken metacarpal, but it is not so easy to answer for a chronic overuse injury, but often there is no room to express reservations or ranges of possibiltis.

    In Australia, our major welfare body Centrelink sat down with doctors a few years ago and completely redesigned their forms, making massive improvements for everyone (doctor, patient, and Centrelink) — so maybe it’s as simple as sitting down with researchers and working out a better way to ask the questions.

  27. Stelita said,

    March 28, 2011 at 11:32 am

    We were just talking in the pub on Friday about how the supposed ‘fast-track’ ethics approval for pandemic flu research in 2009 still took months. Unfortunately the virus wasn’t holding off about while they were deliberating.

  28. AdamJacobs said,

    March 28, 2011 at 1:18 pm

    @chris lawson:

    I appreciate that as someone who is used to reading the application forms, I’m at an advantage over a rookie researcher. However, I really, really don’t think the form is difficult to fill in: it’s just that many researchers don’t make the effort. If it says quite clearly above one of the questions “Do not simply copy and paste the protocol”, then how hard can it be to do something other than copy and paste the protocol?

    Most questions come with very clear instructions, which are frequently ignored.

    Which specific questions do you think are difficult?

  29. bladesman said,

    March 28, 2011 at 5:03 pm

    @ Adam Jacobs

    I agree that the forms are reasonably straight forward to complete. However, in my experience it is often the REC that is guilty of not making the effort. In the last study I (successfully) put through, the response letter to the board required me to address 13 concerns, 12 of which simply referred to the Committee to the appropriate sections of the form! IMHO the main bugbear facing researchers is consistency between RECs and proportionality – it takes me as long to get a focus group study dealing with non-contentious issues through as it does a study using MRI or collecting genetic data. No one in their right mind would argue against the need for the process – it’s more the process itself that needs streamlining.

  30. jodyaberdein said,

    March 28, 2011 at 8:05 pm

    RE: 26

    ‘clinicians can prescribe medications and perform procedures without approval, but as soon as they try to measure the outcomes of their procedures they face a significant bureaucratic hurdle’

    I’d be interested in the thoughts, particularly from those with experience on ethics committees, on the following:

    Proposal – it is unethical to offer or perform any treatment that is not evidence based outside of the context of the most appropriate trial or research setting required to generate the necessary evidence.

  31. AlexG said,

    March 28, 2011 at 9:05 pm

    RE: 29

    “it takes me as long to get a focus group study dealing with non-contentious issues through as it does a study using MRI or collecting genetic data. No one in their right mind would argue against the need for the process”

    I might actually go further and say it can be *harder* to put through a non-contentious focus group study than one with a significant medical intervention. Since studies are frequently evaluated by RECs who aren’t really that knowledgeable about the subject area, a very technical study on genetics, for example, can get evaluated by non-geneticists who aren’t sensitive to methodological flaws that geneticists would spot.
    On the other hand, focus groups are (perceived to be) just a bunch of people talking and every layperson (thinks they) can understand that, meaning that a REC can be more likely to pick holes with that kind of study.

  32. Craig said,

    March 29, 2011 at 4:33 am

    @bladesman: I’m an animal-based (rats) psychopharmacology researcher, and I’d say that there’s also a problem with the ethics committees lacking the expertise to evaluate the proposals.

    I routinely get responses from the ethics committees along the lines of “we don’t like Y; why don’t you do X instead?”, when the answer to that proposal is “we’re not doing X because it’s an incredibly stupid idea that wouldn’t work, and anybody who has ever done this sort of research would already know that”.

    My big problems with the ethics committees I deal with are:

    1) The slow turnaround. Meetings are held, at best, monthly: this means that you spend a week writing up an application, wait a week for a response, find out that you were rejected for some daft trivial reason…and then have to wait another three weeks or so before you can even try to get them to consider the revised version. Getting anything through ethics routinely takes several months; this is obviously a problem when you’re trying to do cutting-edge research in a fast-moving field.

    2) The lack of experimenter involvement in the deliberation. Half of the objections I get could be dealt with in a second if I was at the ethics meeting to answer their questions directly; however, I’m not invited to participate. I’m not even allowed to observe.

  33. AdamJacobs said,

    March 29, 2011 at 9:17 am

    @bladesman:

    Yes, you have a valid point. Some RECs are better than others. If I were running NRES, my main priority would be to figure out why some RECs are underperforming and sort it out.

    However, a tip: I’m not 100% au fait with the way in which particular research projects get assigned to particular RECs, but I believe that in some circumstances, the researcher can choose the REC. Figure out which RECs are sensible and which are not, and then choose appropriately.

    But another thought on your specific experience: can you put your hand on your heart and say that this was definitely the REC not taking the trouble to read the form? Or is it possible that if you’d spent a bit more time making the form easier to read, some of those questions wouldn’t have been asked? Obviously I don’t know what was on the form in your case, but many of the forms I’ve seen are unclear and contradictory, and even if the information is on the form somewhere, it’s hard to be sure you’ve found it and understood it correctly.

    @jodyaberdein:

    That’s an interesting proposal. In one way, I’m tempted to agree with it. Clearly it would be better if non-evidence-based treatments were not used, or if they were used, they were used in the context of a trial. However, I do worry about the practicalities of that. There are an awful lot of non-evidence-based treatments in use. Setting up a trial for each of them would be a pretty tough task, and one which is probably not really feasible. Some efforts towards that ideal would, however, be possible and desirable. The question is how far you could get.

    @Craig:

    I think you may have hit on a difference between animal ethics committees and human ethics committees. If you were doing research in humans, you would always be entitled to attend the meeting and state your case to the committee. I didn’t realise that that wasn’t possible for animal research, and I agree that it’s a shame. It’s always helpful for everyone concerned when researchers attend the meeting, and I can’t understand why animal committees take a different view.

    But as for your first point about “we don’t like Y, why don’t you do X instead?”: well, that may well be a stupid question for anyone who’s an expert in the research area. But bear in mind that ethics committees, at least for human research, cannot always be expert in the research area. They are required to review applications from a range of disciplines, and there is no way they can have expertise in all of them. Applicants need to bear that in mind when writing the application form, and make sure that everything is explained such that someone who is not an expert in their particular subspecialty can understand clearly what is being proposed.

  34. chris lawson said,

    March 29, 2011 at 10:21 am

    joyaberdein @30:

    I think this is a really interesting question. My opinion (although I haven’t worked on any ethics committees): it should be considered unethical to subject patients to untested treatments *without the patients’ consent*. The reason I add the qualification is that sometimes patients will find themselves in a situation for which there is incomplete or contradictory evidence, and the simple formulation of “untested=unethical” would leave these people without any treatment options at all.

    It also leaves open the question of what counts as adequate testing. Ideally every treatment we recommend would be supported by several well-conducted SRs of many well-conducted RCTs. In practice, only 1% of everyday medicine meets this standard (I just made that number up, but it feels about right to me — maybe 5% if one is feeling optimistic). In the absence of ideal evidence, we have to deal with uncertainty, so un- (or under-)tested treatments are going to play a valuable role in medicine until the heat death of the universe.

  35. bladesman said,

    March 29, 2011 at 11:29 am

    @ AlexG
    Good point!
    @Adam Jacobs
    Yes there is indeed a choice of Committees and as you point out, we have learnt which ones to avoid. The fact that we have to do this highlights my point about inconsistency.
    I agree that not everyone takes the time to write a clear proposal and appreciate that each REC have a huge amount to read for each meeting. We do take pains to make things clear and often consult user groups over things like PISs (dodgy acronym!) to make sure of this. And yes, when we get questions in our letter of provisional opinion about, for example, how we calculated sample size yet have several paragraphs detailing this in the section ‘sample size’, I would say we are not the guilty party . Most RECs are great and act as an objective second pair of eyes – it’s the ones that don’t listen, are downright rude or cause unnecessary extra work that give us the headache

  36. Craig said,

    March 29, 2011 at 12:44 pm

    Adam: for the example I had in mind, the bit of “expert” knowledge was, roughly, “stimulant drugs taste bad, and rats won’t voluntarily eat bad-tasting things”. If I have to foresee and counter all possible objections at that sort of level, every ethics application I write is going to be the length of an encyclopedia.

    Yes, there is a need for thorough ethical oversight of research. But the ethics systems as they currently stand are a textbook example of bureaucracy out of control.

  37. Bozo said,

    March 31, 2011 at 3:17 pm

    As a junior doctor I often find myself discussing research ideas with colleagues, and I’m afraid that no matter how simple, easy, safe or downright brilliant a research concept is, most conversations end along the lines of ‘But it will need ethical approval so it’s just not worth the hassle’. It simply isn’t feasible to attempt to get ethical approval for studies within the 6 month timeframe of most of our attachments. First we have to battle with the local R and D department before we’re even allowed to approach the ethical committee, then we have to back to R and D for local approval AGAIN after ethics have approved it. Each stage includes a morass of paperwork and delay. The NRES form, unwieldy as it is, forms only a tiny part of the overall process.
    There are thousands of small scale but useful studies out there being ditched because the ethical approval process is too tortuous.

  38. mikewhit said,

    April 5, 2011 at 1:20 pm

    So from the “Why don’t you do X” behaviour, it would seem to be best to actually indicate as part of the application, why superficially feasible alternatives *at each stage* are not possible / do not work / would not be valuable / are not considered further etc.

    OK, it’s more work but it also shows you have thought about all the background and possible alternatives, and might save time …

    Or, maybe the “why don’t you do X” is just the committee’s way of trying to show it has read the application; just not very thoroughly.

  39. gdvallance said,

    April 7, 2011 at 9:33 am

    OK, first things first — who am I (so you can put my comments in context). I am an ex-member of various NHS RECs with some five years of experience. Its been a couple of years since I was last on a committee. My day-job is largely clincial trials coordination — i.e. I manage clinical trials. So I have to use the research governance framework which Ben criticises. I also have post-graduate qualifications in bioethics (Masters) and ethics and the philosophy of science (Ph. D.)

    I am also writing this *very* quickly, so it might not be as coherent as it should be …

    1. The research governance framework does have many issues. However, these days the problem is *mostly* not with the RECs, rather the R&D Departments. I speak from experience. e.g. one substantial amendment for research I manage took over a year to get approval from one Trust …

    2. Do not equate research governance with RECs. RECs are one element of the entire system. While it is a convenient short-hand it is misrepresentative. Consequently, I want to take issue with what Ben says above:

    “i think one of the most disturbing aspects of this whole process is the reluctance of the ethics committee community to engage seriously with this issue. for example, our anonymous head of a REC above cites the AMS report as if it was favourable about the status quo, when in fact it identifies serious problems, and says (quoted in the Plan For Growth):

    “UK health research activities are being seriously undermined by an overly complex regulatory and governance environment”.

    A new pathway for the regulation and governance of health research, Academy of Medical Sciences, January 2011″ See #7 above.

    If you go to Section 2 p. 6 of the report referred to in Ben’s quote, the Report blames combined regulatory regime *not* RECs particularly.

    “The combined regulatory requirements of the EU Clinical Trials Directive, European Medicines Agency (EMEA), UK Medicine and Healthcare products Regulatory Agency (MHRA), NHS ethics committees, R&D offices in NHS Trusts, the National Information Governance Board and other agencies are stifling UK R&D in both the private and public sector.”

    Moreover, the Academy of Medical Sciences has recently published another report on the Governance system ‘A new pathway for the regulation and governance of health research’ See: www.acmedsci.ac.uk/download.php?file=/images/publication/Anewpath.pdf

    Interest declaration: I made a submission to this report. FWIW, largely critical of the governance system, esp. the R&D element.

    I have not investigated, but it seems that the Coalition Governments proposals, which Ben welcomes, is based on this report. (It was commissioned by the Govt., see p. 2.) It proposes a Health Research Agency, which appears to be the same as the Health Research Regulatory Agency.

    This report notes that RECs have improved significantly. They say:

    “There was clear consensus from the responses received that the process for ethics review has been dramatically enhanced in recent years through streamlining of the process and the introduction of timescales.” See section 8.1 p. 76.

    Although they do go on to say (in the next sentence):

    “However, some respondents raised remaining concerns about review by NHS Research Ethics Committees (RECs) including the lack of proportionality in the system.”

    I should point out that NRES have been piloting a system of proportionate review. I am not sure whether this is operational yet for the entire system. Certainly, the intention is there to make it so, and if/when it is, this point will be addressed. (It might be delayed by the changes proposed …) Anyway, getting on …

    3. The requirement to gain a proxy consent for research on subjects without capacity to consent, which Ben criticises and blames the RECs for in the article, is now *not* a REC requirement but a legal one. Although, to be fair to Ben, the legal obligation may not of existed at the time of the CRASH trial.

    It has been a legal obligation since 2004 and 2005 respectively in England and Wales. I am not familiar with Scottish legislation, but it appears that it has been a legal obligation there since 2000. I.e. The Adults with Incapacity (Scotland) Act 2000.

    The reason for the two dates in England and Wales is because the requirement for proxy consent first became a legal obligation for controlled trials of investigational medicinal products (CTIMPs) under the The Medicines for Human Use (Clinical Trials) Regulations 2004. (See: www.legislation.gov.uk/uksi/2004/1031/contents/made) The relevant part is part 5. This regulation is to implement the European Directive 2001/20/EC.

    It then became a requirement for non-CTIMP research under the Mental Capacity 2005. (See: www.legislation.gov.uk/ukpga/2005/9/contents) The relevant sections are 30-34.

    So since 2004/2005, in England and Wales, the RECs are not to blame for insisting on proxy-consent where adults lack the capacity to consent.

    4. The issue of participation in research without informed consent *is* a difficult issue, where there are legitimate differences of opinion, which the RECs should not be criticised for reflecting.

    I’ll not argue for this point, now, but will if there is demand. Hopefully, why it is a difficult is self-evident to readers of this blog. It should suffice to say, as a starter that history plays a part, and this is even before we get to the philosophical issues.

    Dr. Grant D. Vallance

  40. doctorwithwound said,

    April 20, 2011 at 11:18 pm

    @ Alex G – Excellent point. I saw a patient today inquiring about the distressing, but admittedly cosmetic, appearance of her abdominal striae gravidarum (“stretchmarks”) following her recent pregnancy and delivery. Would vascular laser treatment help, she asked ? I happen to be preparing a forthcoming lecture on laser scar revision to experts and have recently reviewed all the relevant literature (via Pubmed and hand searching etc) on scars and laser treatment. There is nothing to help her, or me,or her, on condition -
    No trials at all, indeed not even any quality low-level evidence (if such a creature exists) – perhaps cocoa butter massage at best. Almost 90% of women get stretchmarks after childbirth so it’s not exactly uncommon. There is some literature on risk factors but very little on treatment. What do I do ? I have considerable experience in treating other types of red scars with laser and some similar striae. Should I refuse to offer treatment for lack of evidence? Should I “experiment” on her outwith an organized trial? I would love to muster the ethical arguments each way but I am a very amateur (tho’ keen) philosopher. In the end, of course, I explained the options, had a reasoned discussion, and we came to a decision – wait a bit longer and review. Was I ethically wrong to decide in the absence of evidence?

  41. vasiln said,

    December 4, 2011 at 12:16 am

    I work in the US, and I have no doubt that there are differences between ethics considerations in the US and in the UK– but it sounds like there are an awful lot of similarities as well.

    I think one thing that ethics organizations ignore is that every medical professional is engaged in non-stop research. When we do something that’s in line with what we know, and don’t get the outcome we expected, we remember it. When that continues, we change what we’re doing. It might not be good research (it’s awfully poorly controlled!) but it’s research, and every time we acknowledge the importance of experience, what we’re doing is affirming that the body of organized medical knowledge that we get in school is insufficient to do our jobs. Medicine is frequently described as both art and science– but what we want to do is turn as much of the art as we can into science! That way, we can tell the difference between a good doctor and a bad doctor, and we can teach our students rather than sighing, “One day, you’ll understand,” and maybe, if we’re lucky, we can get computers to do more medicine and doctors can get a little bit of sleep :)

    The problem with ethics considerations out of proportion to ethical risk (Goldacre describes this perfectly in the example of two treatments that are both acceptable) is that the only thing we’re doing is restricting professionals from performing good research rather than bad research. We still try to figure out what treatment to use in different situations– we’re just careful about how we phrase things, and we don’t write it down, and we don’t randomize our controls.

    Unethically designed experiments exist, and they get caught. But I think what’s been ignored is that it can be just as unethical to prevent research. Insisting on all of the same checks for research regardless of how acceptable the various interventions being researched are is not just stupid, it’s wrong. It is responsible for slowing the development of medicine, and that means reduced quality of life, reduced autonomy, and even, yes, death. This is not a situation where it’s best to err on the safe side, because there is no safe side.

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