HSCT Citizens’ Jury

H

Prof G, why do you talk with a forked tongue?

I am taking stick from many readers about my stance on HSCT. I implied in a comment yesterday that I would seriously consider it as a first-line treatment if I had MS, but in reality, I don’t offer or support HSCT for my own patients with MS as first-line therapy. Some readers are accusing me of double-standards. Should I walk the talk and put my head above the parapet or keep quiet? I have a potential solution; read on …..

The issues around HSCT are complex. HSCT is not a mainstream treatment for MS but will become so when more evidence emerges about its relative efficacy and safety when compared to other licensed DMTs. To address this question we will hopefully be starting a head-2-head trial of alemtuzumab vs. non-myeloablative HSCT in the near future.

At the moment HSCT is available to pwMS under the NHS, but not as first-line therapy. Why? It positioning as a 2nd- or 3rd-line therapy was made by consensus, albeit an HCP consensus, and the current opinion is to limit NHS access to HSCT to pwMS who have failed at least one high-efficacy DMT. I personally don’t agree with this. Provided pwMS are well informed and understands the risks of HSCT and are prepared to take the risks they should be able to have HSCT. There is no doubt that it will be cost-effective; as a one-off treatment, HSCT costs between £28,000 and £30,000. When you compare this to the annual and cumulative costs of some of the other DMTs HSCT becomes very appealing. The downside as always are the risks, and some would argue the risks are too great. Who should be taking the risks; the person with the disease or the HCP? I know where my allegiances lie.

When you have a disconnect between the needs, or implied needs, of the MS community, and the position of the NHS and/or the HCPs there is a potential solution for this problem called a Citizens’ jury. This is when a group of people from the general public (not people with MS or vested interests) decide policy on behalf of pwMS and HCPs; in other words, citizens decide if the NHS and/or HCPs are right to withhold an effective treatment from pwMS based on its costs and/or safety profile. At the moment most CPs feel HSCT is too risky to be a mainstream treatment for MS.

What I am proposing is that we set up a Citizens’ jury that looks into the question of whether or not HSCT should be available for pwMS, who have active MS, as a first-, second- or third-line therapy. If the jury says ‘yes’ then the NHS should create the necessary capacity to deal with the needs of the MS community. I  think the NHS may support the results of a Citizens’ jury as it is win-win for them. Firstly, they will be viewed as being proactive in supporting MSers wishes and if they have to make HSCT widely available as a treatment for MS it will save the NHS money; potentially lots of money. From a person with MS’ perspective it will also be a win-win; i.e. (1) they will have the option of being treated with potentially the most effective DMT under the NHS and (2) they won’t have to cover the private expenses of having to travel abroad to have HSCT. Accessing HSCT under the NHS will also make it more equitable. What about the HCP or neurologist? Is it a win-win for them? Or a lose-lose for them?

Interestingly there was a very well written opinion piece in last week’s BMJ on the use of Citizens’ juries. It is worth a read.

Jacqui Wise. Citizens’ juries for health policy. BMJ 2017;357:j2650

…. What is a citizens’ jury?

….. Citizens’ juries (or community juries or citizens’ assemblies) aim to give ordinary people a role in democratic decision making. They usually consist of 12-20 randomly selected and demographically representative people, but some have had as many as 100. They explore difficult policy questions for government, charities, or think tanks. They differ from focus groups in that participants should be given reliable information and time to deliberate.

…. Malcolm Oswald, director of the Citizens’ Juries community interest company, a social enterprise supported by the University of Manchester, says, “Citizens deliberate among themselves, and, as they become better informed over several days, their views often change.”

…. They are particularly helpful for considering controversial and value-laden questions. For example, the Irish parliament formed a 99 member jury to advise elected representatives on ethical and political dilemmas including abortion, climate change, and provision for an ageing population.

…. What are their strengths?

Citizens’ juries involve the public in decision making, providing diverse experiences and perspectives, and the process can be thorough.

What do you think? Should we lobby the NHS to have a citizens’ jury on the issue of HSCT as 1st-line treatment for MS?

About the author

Gavin

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

26 comments

  • Can I put AIMS forward to participate in this Citizen’s Jury, Gavin? You can contact me directly if this would be of interest. I think we could bring a lot to the table! Alison

  • Great initiative!

    A naive question to help my understanding. You have kindly answered my last question regarding the What is End Organ Damage post by saying:
    “We don’t know. Clearly, the intensity of T-cell depletion may be important because myeloablative HSCT is superior to non-myeloablative HSCT that looks better than Alemtuzumab”.

    Now if myeloablative is superior (?), why compare the non-myeloablative to alemtuzumab in the head to head study you are envisaging?

    • Safety; even the haematologists were against myeloablative HSCT. In an ideal world, you would want to have 3 or 4 arms – myeloablative HSCT vs. non-myeloablative HSCT vs. Alemtuzumab vs. Ocrelizumab.

      • In the absence of a clinical trial (which will probably take 5 years from today until publication), can we not collect existing data on HSCT from the likes of Prof Murraro and compare it to your Barts alemtuzumab cohort?
        Example: compare the MRI scan after 5 years of 30 HSCT to 30 alemtuzumabers, where baseline EDSS wast between 3 and 5.

        Isn’t an observational study the lowest hanging fruit to answer these question?

      • So is there any point in doing the non-myeloablative? In the MIST trial I think they employed this method. I guess the results point to it being more efficacious than ocrelisumab. If one compares data from separate trials – maybe like a metastudy – are there indications that point towards non-myeloablative HSCT being more efficacious than alemtuzumab? Thanks for all your efforts to inform us about MS. I really appreciate it!!

      • I’ćm really curious, what is the reason that you didn’t include Cladribine? As it targets also T cells (which are obviously becoming an important target after B cell-only depleters are inferior to NIRTs). I would say that it could be even better than Ocrelizumab? Especially now that there are hints of loosing OCBs after Cladribine and that there isn’ćt such an effect known for Ocrelizumab/rituximab…

        • Cladrabine’s impact on T-cells is modest; at the licensed dose it drops them by ~50%, which is not low enough to put people at risk of opportunistic infections. Ocrelizumab takes T-cells down by ~15%. These agents are more B-cell specific.

          • My point exactly (I was referring to your comment about head-to head study of HSCT, Alem and ocrelizumab, not why you think that HSCT and Alem are superior to Bcell only depleters). If you believe that T cells are important, then why include Ocrelizumab but not Cladribine in the (hypothetical) head-to-head trial?
            If we look at the T cells as a potential reservoir for EBV, then getting rid of >50% of that (2 times, or even more if there is a disease breakthrough after 2 years) is surely better than reducing them by only 15%?

          • The trial design at present is alemtuzumab vs. HSCT. However, we are seeing a big swing away from alemtuzumab to ocrelizumab and hence the possible need to include it. I have no problem with including cladribine; at the end of the day, we need to be pragmatic. Cladribine does have a remarkable safety profile and is hence a big game changer at a systems level, i.e. if we can get the majority of neurologists to use it as a platform therapy. At the moment ocrelizumab seems to be occupying this slot; it is extraordinary how many patients with active MS are choosing this treatment.

          • “I have no problem with including cladribine; at the end of the day, we need to be pragmatic.”

            I believe it would be useful, especially if getting rid of OCBs is shown to be a robust effect after all.

            “Cladribine does have a remarkable safety profile ….. At the moment ocrelizumab seems to be occupying this slot; it is extraordinary how many patients with active MS are choosing this treatment.”

            I can tell you from experience that this is also a Neuro driven effect: they have less problems with offering Ocrelizumab, but are more reluctant to use/suggest Cladribine/Mavenclad … Alem or HSCT is not even on the table for majority of risk averse Neuros (again, personal experience).

            I’m really curious about your reasoning for favoring Ocrelizumab over Cladribine? There were no head-to-head studies so directly comparing efficacy data is really difficult (as MouseD’s post a few days back highlighted).

          • Unfortunately, cladribine is licensed on the NHS for highly-active MS, compared to alemtuzumab and ocrelizumab that are available as 1st-line therapies for active MS. Also, the power calculations are done using alemtuzumab data. One would argue that the ocrelizumab data mirrors alemtuzumab’s data in relation to its relative efficacy on the components of NEDA and NEDA itself. Cladribine doesn’t, therefore, including it in this trial will affect the study in many ways that are unpredictable. Saying this it would be great if we could add a cladribine arm and increase the power to address this question.

    • Unfortunately, not! The people who participate need to have no conflicts of interest or prior knowledge. The idea is to educate the jury and then allow them to hear arguments from all sides before voting and making a recommendation. A proper citizens jury when resources well and done vigorously usually provides a very good answer. For example, it may say it is too early to recommend wide access until more trials are done. Or it could say the evidence is so overwhelming and the cost-savings so impressive that the NHS should make it available ASAP.

      • How would it work? Who would oversee it? Would it be something like an APPG (All-Party Parliamentary Group) but for citizens? Wouldn’t some level of expertise be necessary?

      • I would invite you to look at The Russia for MS and Autoimmune diseases,Also Mexico,and just see the thousands of wonderful results 75/90% of people have achieved through HSCT non mylo chemo you will be amazed,surly to god this should be all the evidence you need,as it is now, you are costing people healthy lives by delaying it time after time,when this evidence should be enough,also by delaying this treatment to halt the progression,you are all putting people under enormous stress by having to raise the funds,some are selling there retirement plans,houses,and others trying to fund raise for years and they are having relapes the longer they wait,I beg you to step up and take the lead to put your back behind it and support HSCT for all and give us our lives back please, Kind Regards Helen

  • I see that you are still using the word *active*. Patients are going abroad because they are turned down by the NHS for not having *active* MS.
    Therefore nothing will change!!

      • Please will you define “inactive”. I don’t believe there is any such thing as inactive or mild when describing MS.

        MS is always inactive or mild until it’s not and the deterioration happens to cause new lesions or demyelination.

        Lesions are merely one symptom of MS, and to use them in isolation to measure disease activity, is quite frankly, a nonsense and insulting to pwMS.

  • HSCT is not something I would consider for my slow PPMS. I do not believe my constitution would tolerate any such aggressive treatment. HSCT may be a good option for some who have highly active disease – although I don’t know much about the long term effects. (Does anyone?) I just hope that research into potential cures and the “black swan”, such as EBV research, doesn’t become sidelined by what is really just potent immune system destruction.

  • Speaking as someone who has had HSCT for PPMS, and who is also being treated for several other serious conditions, I’m not sure that I have faith that a random collection of people (the People’s Jury) would have enough understanding of the effects of living with such condition to be able to rule on the availability of the treatment. Even many of the “experts” exhibit lack of true understanding, in my experience.

    • That would be my reservation too – but any dialogue has to be a good thing. Surely this would have to be ‘steered’ by people in the know?

    • It is no different from the role a jury plays in a court of law. The legal teams have to explain and educate the jury of the ‘facts’ and the context of the case. The judge adjudicates and makes sure both sides play fair and then the jury decides. By the end of the case, the jurors are experts.

  • Am 50y old male, RRMS for 26y, just started Ocrelizumab after 9y on Dimethyl Fumurate (CONFIRM trial). Wld go onto HSCT in a flash. Wasn’t allowed under NHS as, bizarrely, I am not ill enough.

    I want to get in front of it before I become that ill, not playing catch-up until I kark it. So v v frustrating.

By Gavin

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