Monday, 2 March 2015

Reporting conflicts of interest

Conflicts of interest may affect MSer participation in clinical trials. #MSBlog #MSResearch

"Not surprising conflicts of interests are an important issue and may affect MSers decisions to participate in clinical trials. In many centres there are financial rewards for doing clinical trials; i.e. the income from clinical trials supports the centres and staff who work in them. The latter is particularly prominent in countries without socialist healthcare systems. In the NHS as we are salaried there are no personal rewards for doing clinical trials or recruiting study subjects; however, our hospitals receive the money from doing them. In the past we used to received a small proportion of the so called overheads associated with clinical trials to be used to support research projects of our choosing. Recently, this has changed; all trial overheads are now being taken towards our CIP (cost improvement programme) to help with our large and ever increasing budget deficit. Therefore, there is no direct incentive for doing trials or if there is it is now far removed from the investigators."

"I sit, or have sat, on commercial trial Steering and DSM (data and safety monitoring) committees; this is done in a personal capacity for which I get paid consultancy fees for my time. My commitment to these committees is not linked to subject recruitment, but  obviously my membership in these committees is a conflict of interest. The following is a list of my prior and current commitments to commercially sponsored trials:
  1. Steering Committee Member for the “Oral Cladribine in Early Multiple Sclerosis (MS)” and “CLARITY Extension Study” trial (Merck-Serono) - NOT ACTIVE
  2. Steering Committee Member for the “Safety and Efficacy Study of Daclizumab High Yield Process to Treat Relapsing-Remitting Multiple Sclerosis (SELECT)” and “Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) in Subjects With Multiple Sclerosis Who Have Completed Study 205MS201 (NCT00390221) to Treat Relapsing-Remitting Multiple Sclerosis. (SELECTION)” trials (Biogen-Idec & Abbvie) - NOT ACTIVE
  3. Data and Safety Monitoring Committee Member for the “Efficacy and Safety of GTR in Comparison to Copaxone” trial (Synthon) - NOT ACTIVE
  4. Steering Committee Member for the “Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)” trial (Novartis) - ACTIVE
  5. Steering Committee Member for the “A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Patients With Relapsing Multiple Sclerosis” trial (Roche) - ACTIVE
  6. Steering Committee Member for the “Laquinimod in PPMS (Arpeggio) Study” (TEVA)- ACTIVE
  7. Clinical Advisor for the VSN16 clinical development programme (Canbex Therapeutics), phase 1 and 2a trials - ACTIVE
"What do steering committees do? We help the sponsor design and manage the trial and when the trial is completed we help analyse and interpret the results, present the results at meetings and then write-up the results for publication. Some steering committees have adjudication subcommittees to assess whether study subjects are eligible for inclusion in the trial and to assess whether or not they have had protocol-defined relapses or not. Steering committee members often help with training of investigators and often lead on add-on studies in clinical trials, for example I am the lead of the CSF neurofilament level substudy of the EXPAND and ARPEGGIO trials."

"To address the findings of the study below we will need to start including in the patient information sheet a paragraph about conflicts of interest. I suspect the ethics committees will need to lead on this to make sure it happens. What do you think?"

"My approach to conflicts of interest is transparency and to try and remember to declare them. One of the tabs on this blog lists our current conflicts. Please remember, if you want to be involved in MS drug development it is almost impossible to avoid conflicts of interest, which is one of the reasons the EMA and FDA have such problems finding non-conflicted expert members for their SAGs (scientific advisory groups)." 


Epub: Solomon et al. Patient perspectives on physician conflict of interest in industry-sponsored clinical trials for multiple sclerosis therapeutics. Mult Scler. 2015 Feb. pii: 1352458515569101.

BACKGROUND: Pharmaceutical industry financial support of physicians, physician practices, and academic departments involved in multicenter industry-sponsored clinical trials of novel therapeutic agents is a relatively new and infrequently acknowledged source of potential physician conflict of interest. Detailed disclosure of these relationships to study participants is not uniformly a part of informed consent and documentation practices.


OBJECTIVE: To understand attitudes of MSers concerning disclosure of potential physician-industry conflicts of interest created by clinical trials and how such disclosures may influence study participation.

METHODS: An anonymous online instrument was developed.

RESULTS: 597 MSers participated in the study. The study found that detailed disclosure of conflicts of interest is important to potential participants in industry-sponsored clinical trials for multiple sclerosis therapies and that the presence of these conflicts of interest may influence MSers decisions to participate in these studies.

CONCLUSIONS: Findings from this study support a call for uniform guidelines regarding disclosure of physician-industry relationships to prospective research participants for industry-sponsored clinical trials.

CoI: multiple

16 comments:

  1. I've a question. Given what you've said about the need for hsct to be trailed against Alemtuzumab to decide whether it's worthwhile, does it not rub you up the wrong way to be part of a trial design panel who've chosen to test Ocrelizumab against... Interferon beta? Why not Lemtrada or Tysabri instead?

    Genuine question.

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    1. I'm making assumptions here, and ProfG will know the full story, however (i) Roche will want to show superiority against a standard of care, and to beat IFN beta should be reasonably straightforward, (ii) Roche are probably planning to submit for first line license, whilst Natalizumab is more often used - and nationally approved (such as in the UK) - as second line treatment only (exception: RES MS), and (iii) the Ocrelizumab program commenced before Dimethyl-Fumarate, Teriflunomide and Alemtuzumab became licensed first line alternatives. I agree, from an MSer's perspective showing *non-inferiority* against Alemtuzumab would be the real test for Ocrelizumab, and could be a winner given Alemtzumab is a highly effective drug. If Ocrelizumab were equally effective, however safer than Alemtuzumab (quite likely given the risk of secondary autoimmunity on Alemtzumab), Ocrelizumab might just sweep the market. I suspect the risk it might - for whatever reason - fail on efficacy against Alemtuzumab, and the associated cost (drug + oncosts) makes such a trial commercially unattractive.

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  2. This is timely given the recent issue about two senior Parliamentarians. My comments aren't directed specifically at Prof G, but raise some wider issues:

    (I) as with case of an MP is a neurologist job a full time job? NHS doctors always claim that they are overloaded, but there seems to be plenty of time to do all this advisory / paid work.
    (ii) i'm guessing a consultant neuro gets more that the £67,000 of an MP. Is there really a need to do all this extra fee paying work?
    (Iii) i don't think the COI issue is about simply declaring it. The issue is money. I have no idea how much all this advisory work brings in. If company x was paying you a couple of thousand pounds to read some pares etc. i would feel comfortable. If the same company were paying you tens of thousands of pounds, i would feel less comfortable, particularly if I was being advised to start one of their drugs.

    (IV) the major issue I have is that a neuro getting a NHS salary plus an academic salary plus a large number of fees from variuos companies equates to a very large income (bear in mind that the average UK salary is £28,000 a year). This is a disease where, for the progressive stages there are no treatments and patients and their families have to watch the deterioration. The fact that good money is being made out of this situation leaves a bad taste in the mouth.

    Please note: this is just my humble opinion. I've no doubt that lots of hard work is undertaken. But at the end of the day conflicts of interest comes down to money.

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    1. So true. MS is a thriving business.

      It really disgruntles me that the people running this blog and raving about new DMTs have also fiscally profited in some ways by steering the development of these medicines. Where is the impartiality?

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    2. The conflicts involved for doctors in the NHS are relatively minor when compared against most doctors working in private healthcare systems where the doctors pay is related to many factors within the doctor's control. So they get more money for more patients examined, treated and investigated. This equates to many more pointless investigations, treatments and also increases the complexity of all of these as there is money to be made by increasing all of this.

      People are making money from other people's ill health all over the world. The NHS and its doctors are relatively small fry when it comes to this. It can definitely be distasteful and unethical when people do more than is required simply to make more money. Remember all of this when you're voting as the Conservatives believe that someone/some company/some group of shareholders should be making money of all of our ill health in the UK.

      It can be a fine line, but the NHS reforms will tilt it all towards private money... the doctors probably won't benefit greatly from this (though doctor's pay in the end is often higher in private systems).

      Academic medicine, by the way is often thought to be in crisis in the UK as the pay can be relatively poor for the remuneration available, and the job can be a considerable hassle and highly stressful as universities demand a certain number of studies and journal articles per year.

      The bottom line is that things in the UK aren't perfect, but they aren't that bad. I come from both sides of the fence when it comes to this blog and its subject matter. I've seen doctors quit academic medicine and have also seen many leaving the UK due to changes over the last number of years. I'd love to see decent doctors retained in the UK and decent people encouraged to continue their academic work.

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    3. An excellent comment. I entirely agree with you.

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    4. To the the best of my knowledge very few NHS neurologists sit on trial steering committees. They tend to have their jobs planned to account for every 15 minutes of their programmed activities (PAs). NHS consultants supplement their income by seeing private patients after hours or on weekends; this provides a much regular income for them. Some NHS consultants are able to carve out academic PAs in their job plans, but these are usually paid for by other funds and not from routine NHS budgets.

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  3. I don't know if it is done or not, but I think that all data arising from trials should be given as raw data to independent number crunchers to see if their findings concur with those who ran the trial. If it doesn't, then questions can be asked, and this should help with reducing any bias that may be introduced as a result of conflict/s of interest.

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    1. Check here for an initiative supporting publication of all trial data: http://www.alltrials.net/petition/

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  4. Prof G why don't you be open and report your financial earnings from pharma here

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    1. http://multiple-sclerosis-research.blogspot.com/p/conflict-of-interests.html

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    2. this doesn't tell me how much he's actually getting. if it's £100 who cares but if it's £100,000 then clearly that's an issue. physicians in the US are doing this.

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    3. how does prof g compare to this guy- http://time.com/3714242/candidate-to-lead-fda-has-close-ties-to-big-pharma/

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    4. why doesn't prof g do the decent thing and give the money earned to the charcot 2 project? if he does i will match it.

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  5. " ... transparency and to try and remember to declare them...' -

    And to be vigilant that clinical decisions are not affected ?

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