Sunday, 26 January 2014

Risk sharing scheme: does the DoH deserve to get its money back?

The Big Pharma Exodus. Have we shot ourselves in the foot? #MSBlog #MSResearch

"You will find the paper below interesting. It describes the methodology the next analysis of the UK Department of Health's (DoH) risk-sharing scheme (RSS). The RSS was out in place to allow MSers access to DMTs after NICE (National Institute for Health and Care Excellence) had ruled that interferon-beta and glatiramer acetate were not cost-effective for the NHS."

"The RSS was a political solution to a very tricky problem. NICE was meant to prevent postcode prescribing, i.e. access to medication depending on where in England and Wales you lived. The problem with MS is that the horse had already bolted and there were several thousand MSers on IFN-beta when NICE made its ruling. This created a perverse situation with MSers already on IFN-beta being able to stay on treatment, and nobody else being able to access the drugs. This caused an uproar. A threat of a legal challenge by a few MSers was all it took to get the DoH to change its stance. It was clear that the DoH would have lost its case in either an English court, or on appeal in an EU court. Denying some MSer DMTs when others were on them is against the laws of the EU. The DoH recapitulated and the RSS was born."

"The RSS is a simple idea, but flawed in its implementation. The idea is to see how the drugs work in the real world. The problem is you need to compare the RSS data to something. Initially the plan was to compare it to the London Ontario historical natural history study. This cohort proved unsuitable; rumour has it that the data was imputed and that the EDSS in this database did not behave as it should. For example, you can only get worse on the EDSS in the London, Ontario, database when real-life experience shows the EDSS is a wobbly score with improvements (regressions) as well as progressions. The DoH RSS has now turned to the British Columbia Multiple Sclerosis (BCMS) database as its comparator. This database has been heavily criticized by commentators in the field as MSers in this database behave in a benign way; this database is an outlier. This has problems for the RSS. If you compare how MSers do in the RSS with MSers in  the BCMS database and find no difference is it because the drugs don't work or is it because the MSers in BCMS database have benign disease? Why is this important? It is important to the Pharma companies involved because if they don't show the RSS MSers doing better they are going to have to lower the price of their drugs. It will also create the impression that these drugs don't work. I think we now have enough data from trials, and real-life MS registries, to counteract this argument at an International level, but at a UK level the therapeutic nihilists will use this to say 'we told you so' and to try an extract resources out of the RSS to be used elsewhere. The latter is a potential problem because the RSS has helped MSers enormously. The RSS has been responsible for revolutionising MS services for MSers in the UK, by providing access to specialist care and information which has benefited the whole MS population, whether or not they are on drug therapy. The RSS has created 100s of MS Specialist Nurse posts; a recent estimate puts the numbers of MS specialist MS nurses in the UK at around 270. The RSS has also created a network of over 70 MS specialist treatment centres, which has been responsible for the data collection for the RSS. What will happen to all these gains if the RSS data shows that treatment with IFN-beta or GA is no better than living with benign MS in British Columbia?"

"Are we shooting ourselves in the foot?"

"The paper below sets the scene for how the data will be analysed in the next phase of the RSS. Please don't hold your breath. Most of us are expecting the comparison to reveal no differences. The DoH will then have a new truncheon with which to beat Pharma into a pulp. Pharma will have yet another reason to justify its exodus from the UK and the UK Plc will be poorer for the loss of yet another industry. Politicians are too shortsighted to realise the impact NICE has had on the Pharma industry within the UK."

"In my centre we run an MSc in translational neuroscience; we teach the students about drug development and how to translate basic discoveries into treatments for neurological conditions. Where in the UK are our graduates going to get jobs? Almost all new jobs in Pharma are being created in emerging markets, Switzerland and the USA. Why? Look no further, the RSS is just one of the reasons for the state of affairs."

Palace et al. UK multiple sclerosis risk-sharing scheme: a new natural history dataset and an improved Markov model. BMJ Open. 2014 Jan 17;4(1):e004073. doi: 10.1136/bmjopen-2013-004073

BACKGROUND & OBJECTIVES: In 2002, the UK's National Institute for Health and Care Excellence concluded that the multiple sclerosis (MS) disease modifying therapies; interferon-β and glatiramer acetate, were not cost effective over the short term but recognised that reducing disability over the longer term might dramatically improve the cost effectiveness. The UK Risk-sharing Scheme (RSS) was established to ensure cost-effective provision by prospectively collecting disability-related data from UK-treated patients with MS and comparing findings to a natural history (untreated) cohort. However, deficiencies were found in the originally selected untreated cohort and the resulting analytical approach. This study aims to identify a more suitable natural history cohort and to develop a robust analytical approach using the new cohort.

DESIGN: The Scientific Advisory Group, recommended the British Columbia Multiple Sclerosis (BCMS) database, Canada, as providing a more suitable natural history comparator cohort. Transition probabilities were derived and different Markov models (discrete and continuous) with and without baseline covariates were applied.

PARTICIPANTS: From the BCMS database, 898 'untreated' patients with MS considered eligible for drug treatment based on the UK's Association of British Neurologists criteria.

OUTCOME MEASURE: The predicted Expanded Disability Status Scale (EDSS) score was collected and assessed for goodness of fit when compared with actual outcome.

RESULTS: The BCMS untreated cohort contributed 7335 EDSS scores over a median 6.4 years (6357 EDSS 'transitions' recorded at consecutive visits) during the period 1980-1995. A continuous Markov model with 'onset age' as a binary covariate was deemed the most suitable model for future RSS analysis.

CONCLUSIONS: A new untreated MS cohort from British Columbia has been selected and will be modelled using a continuous Markov model with onset age as a baseline covariate. This approach will now be applied to the treated UK RSS MS cohort for future price adjustment calculations.


  1. Prof G,

    Thanks for all your efforts. As a patient all I want is highly effective treatments to keep me as well as possible. Friends diagnosed with cancer seem to go to the oncologist and be treated straightaway. Why does MS have to be treated differently. I have no interest in RSS - seems another example of creating unneccessary paperwork and cost. We now have highly effective treatments for RRMS - nataluzimab, alemtuzumab and more on the way. It seems that fate always conspires to prevent patients from getting these treatments and at a time where they can have maximum benefit. I bet NICE don't give Alemtuzumab the green light this year. MS is bad enough without all this approval bureacracy. They should just admit that they don't want to spend money. I hope those countries who now use Alemtuzumab e.g Denmark record the benefits to these patients (fewer relapses, less hospitalisations, less disability) compared with the data on patients using first line injectibles. This will hopefully convince other countries where the only interest is to delay introducing treatments to save money at the expense of patients health.

    1. You are correct. The main aim of NICE and the commissioners is to make sure our healthcare is affordable, i.e. cost-effective. The current models don't take indirect costs into account for example loss of work and your partner needing stop working to become your carer. Nor do they take social costs into account; i,e disability benefits and having your house redone to deal with your disabilities. All they are worried about is how much is it going to cost the NHS. Theoretically, a cure for MS may not be cost-effective if all costs are front loaded. The cost of giving the treatment may be too expensive for the NHS. Isn't this amazing.

    2. Professor Giovannoni, I work for NICE and you are making factually incorrect statements. Please see-
      The NHS has limited resources, by paying for treatments that are not cost-effective is to deprive other patients a cost-effective treatment.

    3. Anon 1:16pm, thank you. I have MS and despair at the way this blog advocates the callousness of health bodies when it comes to withholding treatments they have been involved in developing. This blog is extremely pro-medicine and devalues holistic treatments as simply add-ons. It also vilifies anyone that doesn't agree with its stance.

    4. I agree. NICE exists to ensure we get good value for money. If they don't approve then it's because the drug doesn't work or pharma wants too much for it. Alemtuzumab was discovered in UK universities funded by UK tax payers. It was withdrawn as a treatment for leukaemia so the price could be inflated for MS. That is disgusting and nothing to do with NICE.

    5. I don't understand your arguments Prof G- NICE assesses whether drugs should be reimbursed by the government, nothing else. Why would that make pharma leave the UK? I don't think NICE has stopped any pharma company applying for NICE approval for all of their drugs? or can you please give an example of a drug that has been marketed in all countries apart from the UK?

    6. "This blog is extremely pro-medicine and devalues holistic treatments"

      Wrong...we are what it says on the tin "Interpreting the good bad and other Research news"....the holistic treatments often falls towards the bad because they are so underpowered and lead to no definitive tangible conclusions.

      However always ready to enthuse, you are obviously a "Dre" fan :-)

  2. Most big pharma have already left the country as a site for neuroscience research many companies have moved their operations to the us or east wards, Maybe too much costs or red tape

    It will be interesting iF anything can be clawed back.

    1. That has nothing to do with NICE- they still apply to get all their drugs approved in the UK. There is a NICE equivalent in all countries. The Fed rejected alemtuzumab - I don't think they will leave the US.

    2. I did not say this was NICE...

      Pharma are out to make a buck and so they apply to sell drugs which is their business, but they decide how much they will accept for their drugs, Will they say no you can't have then for that price?

    3. Regarding the new price of alemtuzumab. You have to realise that the pricing of Pharmaceuticals has little to do with the manufacturing costs. It is mostly based on what it costs to develop a drug and how long the patent has to run. What Alemtuzumab cost for leukemia is not relevant to MS; the MS development programme was long, arduous and expensive. If you remove the incentives for pharma, i.e. their ability to make money, you get no drug development. The choice is simple; we either allow Pharma to make money and get new drugs or we enter a pharmaceutical dark age.

    4. Prof G is saying it is NICE. I'm glad you disagree with him too!

  3. What hasn't ProfG had his finger on somewhere in the loop so if he opens his mouth, is he really an ogre for being pro choice

    " It (the blog) also vilifies anyone that doesn't agree with its stance"

    So consider yourself villified then :-)

  4. Prof. G you need to come clean; are you against NICE and the RSS or not? And are you criticizing Prof. Ebers and his London Ontario register?

    1. Re: "...criticizing Prof. Ebers and his London Ontario register/"

      I was only paraphrasing the BMJ Open article, which made the following statement:

      "In retrospect, both the control dataset and analysis model selected, when setting up the RSS, were found to have intrinsic flaws that made them unsuitable for the task.6 The natural history cohort (from London, Ontario, Canada) was unexpectedly found to contain retrospectively smoothed disability data (rather than actual, real-time collected disability scores), censoring any improvement in EDSS. Comparing our uncensored treated cohort to data retrospectively smoothed in this way would have the effect of unpredictably underestimating any treatment effect. In addition, individual-level patient data were not available from the London, Ontario cohort, which prevented precise baseline matching between the two cohorts, limiting our validation of the underlying (Markov) model for disease progression. Furthermore, there were only 342 patients matching the ABN prescribing criteria from which to generate the models."

      For full access to the article:

    2. Re: "Are you against NICE and the RSS or not?"

      This question is a very complex one and I would need to prepare a long statement. My attitude to NICE is a mixed one. It all depends on what hat you want me to wear? With regard to the risk-sharing scheme; it was a good idea, but poorly executed. It achieved what it was meant to politically. It prevented a legal challenge, NICE survived and MSers got improved services. The results the RSS will produce will be confusing and will muddy the waters. Hopefully, we can all learn from the experience.

  5. You say people in the BCMS dataset behave in a 'benign way', however weren't patients chosen from the BCMS dataset to be compared only if they matched the association of british beurologists guidelines for starting DMT's? I.e. 2 clinically significant relapses in the previous 2 years? Surely this would mean that at a population level they would have roughly equal seriousness of disease?



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