MPs call for fresh talks to end deadlock over cystic fibrosis drugBMJ 2018; 360 doi: https://doi.org/10.1136/bmj.k1337 (Published 21 March 2018) Cite this as: BMJ 2018;360:k1337
All rapid responses
Dear Editorial Team;
Over the last 40 years, incremental improvements in the care for people with cystic fibrosis (CF) has resulted in improved survival for individuals with this devastating genetic disease.1 However, in the current decade treatment for CF has made a step change to therapies which correct the cellular defect in chloride transport and could potentially have a transformative impact on morbidity and mortality.1,2 In the UK, ivacaftor has been reimbursed for around 5% of patients with specific gene mutations since 2013. A recent study of UK and US patients with the G551D mutation (the largest group in whom protein function is corrected by ivacaftor) showed improved survival and less requirement for lung transplantation compared to matched controls3.
A combination of ivacaftor and lumacaftor (Orkambi)4 was approved by the European Medicines Agency in 20155 for people with CF who are homozygous for the F508del gene mutation (approximately 50% of people with CF in the UK). This therapy has undergone health technology assessment through NICE and was considered by the Scottish Medicinesby Consortium (SMC). It was found to have efficacy, but the cost was considered too high for the benefit derived by patients.6,7 The main beneficial effect is to reduce pulmonary exacerbations and reduce hospitalisations.4 Protracted discussions between NICE, NHS England and the SMC with the pharmaceutical company which manufactures these drugs, Vertex, have failed to reach resolution and most people with CF in the UK do not have access to this therapy. This was highlighted in March through parliamentary discussion and debate8 and on 9th November 2018, the Chair of the Health and Social Care Committee Sarah Wollaston asked for full disclosure of all correspondence between Vertex, NICE and NHS England relating to the pricing of Orkambi.9
The position in the UK contrasts with most other countries where cystic fibrosis is prevalent. People with CF in the United States, most of Europe and Australia have access to this combination therapy. Understandably, this has led to significant frustration and anger for children and adults with CF and their families in the UK. Concern about access to effective treatment is further heightened by the development of new triple combinations of CFTR modulators which are currently being evaluated in phase III clinical trials (including participants from the UK). Phase II clinical trials suggest these combination therapies will be very effective in people with CF and will benefit around 90% of patients.10 Discussions between NHSE and Vertex have involved a portfolio deal which includes these potentially transformative drugs for the majority of people with CF with the most common mutation, F508del.
As representatives of the UK clinical community, we believe that access to current and future approved therapies for people with CF is critically important. Patients who will benefit from these treatments are being denied an effective therapy which has been approved by the appropriate regulatory body and has market authorisation. We fully support the health technology assessment undertaken by NICE and agree that the combination of ivacaftor and lumacaftor has efficacy. It is however now intolerable for people with CF and their care teams that after 3 years, a fair price has not been negotiated between Vertex and our commissioning bodies in the NHS. It is inequitable that such treatments are available to most of the world’s CF community, but not in the UK. This limits our options as paediatric and adult physicians to provide optimal treatment for people with CF in this country.
Clinicians in the UK want to use these therapies and people with CF wish to be treated with these drugs. It is therefore incumbent that Vertex work with NICE and UK commissioners to strike a fair deal based on the robust health technology assessment undertaken, to enable us to deliver the best care possible for people with CF in the UK.
J Stuart Elborn*
On behalf of the UK Cystic Fibrosis Medical Association.
J Stuart Elborn
Imperial College London and Royal Brompton Hospital
Fulham Road, London, SW3 6HP
1: Elborn JS. Cystic fibrosis. Lancet. 2016 Nov 19;388(10059):2519-2531. doi:
10.1016/S0140-6736(16)00576-6. Epub 2016 Apr 29. Review. PubMed PMID: 27140670.
2: Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, Griese M,
McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe
SM, Dong Q, Rodriguez S, Yen K, Ordoñez C, Elborn JS; VX08-770-102 Study Group. A
CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl
J Med. 2011 Nov 3;365(18):1663-72. doi: 10.1056/NEJMoa1105185. PubMed PMID:
22047557; PubMed Central PMCID: PMC3230303
3: Bessonova L, Volkova N, Higgins M, Bengtsson L, Tian S, Simard C, Konstan MW,
Sawicki GS, Sewall A, Nyangoma S, Elbert A, Marshall BC, Bilton D. Data from the
US and UK cystic fibrosis registries support disease modification by CFTR
modulation with ivacaftor. Thorax. 2018 Aug;73(8):731-740. doi:
10.1136/thoraxjnl-2017-210394. Epub 2018 May 10. PubMed PMID: 29748252..
4: Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo
C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF,
Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT
Study Group. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for
Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. doi:
10.1056/NEJMoa1409547. Epub 2015 May 17. PubMed PMID: 25981758; PubMed Central
8: BMJ 2018;360:k1337
10: Holguin F. N Engl J Med. 2018 Oct 25;379(17):1671-1672. doi: 10.1056/NEJMe1811996. Epub 2018
Competing interests: Conflicts of interest: CE has received speaker fees from Vertex. JSE has participated in advisory boards with Vertex, Galapagos and Proteostasis. He has contributed as a chief and principal investigator in clinical trials of drugs developed by Vertex. All monies for clinical trials are paid to the Royal Brompton Hospital. The Royal Brompton Hospital is in receipt of a NHS England/ABPI innovation grant supported by Vertex which he co-leads. CSH has received consultancy fees, speaker fees and research grants from Vertex. He has contributed as a site principal investigator in clinical trials of drugs developed by Vertex and Galapagos. All monies for clinical trial work go to Royal Papworth Hospital. GC has participated in advisory boards for Mylan and Novartis. He has contributed as a principal investigator in clinical trials developed by Vertex and Gilead. All monies for clinical trials also go to University Hospital Southampton. UK CF Medical Association (UKCFMA) This is an Association of medical doctors in the UK who deliver clinical care to children and adults with cystic fibrosis. The Association formed in 2018. The purpose of the Association is to advocate for optimum care of people with cystic fibrosis in the UK. The Association receives support from the UK CF Trust to undertake it’s activities. It receives no sponsorship from the pharmaceutical industry. This letter was circulated to all members of the UKCFMA and was is endorsed by 98 Consultants from UK CF centres. Three did not support the content. Some members of UKCFMA have contributed to advisory boards and /or been a PI on clinical trials sponsored by Vertex.
MPs have characterised NICE's appraisal system as not fit for purpose following its failure to recommend the cystic fibrosis medication Orkambi for use in the NHS on cost-effectiveness grounds (News Analysis, 31 March). A parliamentary debate was held in response to an online petition by more than 100 000 people. How has this come about? It is because there is a disconnect between the method used by NICE in its economic evaluations and the ethical views of many members of the public.
NICE's overriding aim is to maximise health. That sounds great! But whose health? Not yours or mine, I'm afraid.
NICE's approach is utilitarian. It aims to maximise aggregate population health, treating health as an entity disembodied from individuals. It does this by aiming to distribute health care resources across the population so as to maximise total health gain (allocative efficiency).1 The utilitarian approach is concerned only with the sum of gain and, as Nobel Prize-winning economist Amartya Sen has said, is "supremely unconcerned with the interpersonal distribution of that sum".2
NICE applies a standard criterion for the cost-effectiveness of interventions and thus allocates resources to those people who are lucky enough to have conditions which are treatable with those interventions. For people who cannot be so treated, NICE is identifying, not cost-effective treatments for people, but people who are not cost-effective for treatment.3 This is in contrast to the approach of health care workers, who start with patients and then look for cost-effective interventions to treat them (productive efficiency).1 These are very different things.
Over two millennia ago Aristotle wrote that, for justice, people who are equal (in some relevant respect) should be dealt with equally.4 That is fair. It is like in a tax system where everyone in a given income band pays the same rate of tax. This Is called horizontal equity. But Aristotle went on to say that people who are unequal in a given respect should be dealt with differently in order to mitigate the inequality.4 This is like in a tax system where people of lower income pay lower rates of tax than those of higher income. This is called vertical equity. When NICE applies a standard criterion for the cost-effectiveness of interventions which applies to all people, it applies a criterion of horizontal equity when vertical equity is plainly called for. Vertical equity calls for people with life threatening or other serious illnesses such as cystic fibrosis to have a priority resource claim. Such people should not be sacrificed on the altar of one particular definition of efficiency.
For productive efficiency, the outcomes of different interventions for a particular condition can be measured empirically in natural units (such as mm Hg or deaths avoided) and related to cost. But estimating allocative efficiency involves comparing cost-effectiveness of interventions across different conditions and this requires a generic measure of health gain. NICE uses the anticipated number of additional years of life adjusted for the quality of life in those years - the quality-adjusted life year (QALY). Allocative efficiency is achieved by maximising the sum of QALYs. The generic measure involves a process of compositing the outcomes of death and estimated quality of life. Yet many people would regard death and quality of life as being qualitatively different and incommensurable.5 The compression of frequently multidimensional health outcomes into a single, objectively-unmeasurable number is essentially artefactual. Is it a sufficient basis for making life and death decisions on the allocation of health resources? It seems you are more likely to believe this if you belong to the brand of economists whose professional work depends on it.
Decisions on health resource allocation do not lend themselves to easy solutions because a balance must be found between degrees of affordability, clinical effectiveness, equity and efficiency. But this is not something that should be decided behind closed doors based on – what many would regard as - an arcane formula. The principles to govern such a decision-making process are a matter of social policy and require informed political debate and open public consultation (wider than NICE's Citizens Council). This is not a question of economics. It's a question of political choice.
1. Palmer S, Torgerson DJ. Definitions of efficiency. BMJ 1999; 318:1136.
2. Sen AK. On economic inequality. Oxford: Clarendon Press, 1973: 16.
3. Harris J. It's not NICE to discriminate. J Med Ethics 2005; 31:373-5.
4. Gosepath S. Equality. The Standford Encyclopedia of Philosophy. Standford: 2011.
5. Anand S, Hanson K. Disability-adjusted life years: a critical review. J Health Econ 1997; 16: 685-702.
Competing interests: No competing interests