Will Pharma compensate if their drugs don’t perform

It has been suggested that pharma should pay if their drugs don’t deliver. Would the do this?. M

aybe we can get a hint from the UK Departmentof Health (DoH) RISK SHARING SCHEME,(RSS) which was a fudge to allow access to People in the UK to interferon-beta and glatiramer acetate which were not considered cost effective by NICE. 

Pharma could sell their expensive drugs to people with MS and there would be a pay back if they did not deliver……
This is what ProfG said previously
“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.”

  • In 2002 NICE suggested the UK health authorities and DMT manufacturers consider 
    joint action to allow DMTs to be secured in a cost-effective way for people with MS
  • The target cohort to be monitored of 5,000 patients was reached by April 2005
  • Over 12,000 patients have had access to DMTs through the scheme
  • Over 200 MS Nurse Specialists are now working in the UK
  • Around 12% of people with MS are now on a DMT
  • Results from the first two year data analysis were published in the British Medical 
    Journal in 2009

OBJECTIVE:To generate evidence on the longer term cost effectiveness of disease modifying treatments in patients with relapsing-remitting multiple sclerosis.
DESIGN:Prospective cohort study with historical comparator.
SETTING:Specialist multiple sclerosis clinics in 70 centres in the United Kingdom.
PARTICIPANTS:Patients with relapsing-remitting multiple sclerosis who started treatment from May 2002 to April 2005 under the UK risk sharing scheme.
INTERVENTIONS:Treatment with interferon beta or glatiramer acetate in accordance with guidelines of the UK Association of British Neurologists.
MAIN OUTCOME MEASURES:Observed utility weighted progression in disability at two years’ follow-up assessed on the expanded disability status scale (EDSS) compared with that expected by applying the progression rates in a comparator dataset, modified for patients receiving treatment by multiplying by the hazard ratio derived separately for each disease modifying treatment from the randomised trials.
RESULTS: In the primary per protocol analysis, progression in disability was worse than that predicted and worse than that in the untreated comparator dataset (“deviation score” of 113%; excess in mean disability status scale 0.28). In sensitivity analyses, however, the deviation score varied from -72% (using raw baseline disability status scale scores, rather than applying a “no improvement” algorithm) to 156% (imputing missing data for year two from progression rates for year one).
CONCLUSIONS:It is too early to reach any conclusion about the cost effectiveness of disease modifying treatments from this first interim analysis. Important methodological issues, including the need for additional comparator datasets, the potential bias from missing data, and the impact of the “no improvement” rule, will need to be addressed and long term follow-up of all patients is essential to secure meaningful results. Future analyses of the cohort are likely to be more informative, not least because they will be less sensitive to short term fluctuations in disability.

Whoops there is not evidence of improvement…Are the companies showing evidence of splashing the cash.To save a bit of face they have to bin the Canadian control group who are doing too well

  • 2010 – Potential switch to use of British Columbia comparator dataset to enable more accurate/informed analyses to be made from the scheme in the futureSummer 2010 – The scheme’s 
  • Scientific Advisory Group to sign off the revised Statistical Analysis Plan
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.

Prof G posted 
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”.

It also depends on who does the assessment as it is not always the same, I heard that Alemtuzumab would have done better in phase III trials if one person per centre had made the EDSS assessments.

 “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?”

” Please don’t hold your breath. Most of us are expecting the new 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.”

  • The scheme is scheduled to run until 2015
Will we see a payback….I suspect fat chance…but ist this the way that the DoH intend to pay for newer more effective DMT..or will they have to pay Market Price as in the US if Pharma get fed up with UK PLC.

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  • Sounds like we need some kind of over arching figure or organisation that understands all the issues and is able to influence all the different factors that contribute to the way MSers (and people with other conditions) are treated in the UK.

  • I saw this study a while back on cost effectiveness of DMTs in the United States (http://www.ncbi.nlm.nih.gov/pubmed/21775734), and the conclusion was DMTs in the U.S. are not cost effective by normal measures applied to our treatment of other chronic conditions. However, if we could get them marked down 2/3 to the cost level seen in the U.K. then the costs come in line with other chronic health condition treatments.

    On the idea of repayment if a drug fails, I think there are numerous issues with this. How will we measure failure: new lesions, brain shrinkage, worsened quality of life, greater effective disability score, etc.? I ask this in all seriousness as I work with a web site to develop better measures for patients for tracking disease progression across a variety of medical conditions. We run into problems trying to develop questions and measures to accurately assess health versus illness.

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