The National Institute for Health and Care Excellence (NICE), the body that determines the clinical effectiveness and economic value of new medicines, has increased the cost-effectiveness thresholds it applies for drugs that qualify for their Highly Specialised Technology (HST) programme.
NICE uses ‘quality-adjusted life years’ (QALYs) to quantify a drug’s cost-effectiveness; for standard drugs, their guidelines suggest £20,000 – £30,000 per additional QALY is good value for money, though there are exceptions.
From April 1 this year, the HST programme now applies a more generous threshold, up to £300,000 per QALY, for ultra-rare disease drugs.
Dan Williams, CEO at SynaptixBio, which is developing a drug to treat H-ABC, a rare, deadly, and currently incurable disease, says the change is welcome but that overall the process remains complex.
He notes: “I think everyone understands the need to balance the effectiveness of a drug against its cost, and that there needs to be some kind of metric against which judgements can be made, but it remains the case that some decisions are taken on a case-by-case basis so are open to interpretation.”
Due to high development costs and, by definition, small patient populations, rare disease drugs are typically very expensive, making it a complex and difficult decision to approve them for use in the NHS.
These high prices mean such drugs frequently fail to meet standard cost-effectiveness criteria; today, only 1 in 20 of the approximately 7,000 known rare diseases have an approved treatment on the NHS.
But there are problems even before drugs get to NICE; according to a report from February this year by the Association of the British Pharmaceutical Industry (ABPI), since 2018 only one quarter of rare or ultra-rare disease drugs approved by the Medicines and Healthcare products Regulatory Agency (MHRA) were submitted to NICE for evaluation.
Further evidence that rare disease drugs are struggling to get to market is the decline in clinical trial activity over the last few years.
Dan added: “We know first-hand how challenging it is to bring a rare disease drug to market, as we have just recently selected our development candidate for taking forward into clinical trials.
“The MHRA and NICE form vital parts of the system for ensuring drugs are safe, effective, and economically viable. However, the process is very demanding and, for a small biotech like SynaptixBio, can be a serious drain on resources.”
He continued: “The criteria applied by NICE for getting onto the HST pathway include the requirement that the drug is for a condition that is both ultra rare and debilitating, which despite their best attempts at defining must leave open the possibility of interpretation.
“There are sub-criteria, adding a requirement that the disease is a lifelong condition requiring continuous clinical support, and that is has an ‘exceptional negative impact’, concluding that these things will be judged on a case-by-case basis.”
The UK parliament recently published a post in which it spelled out the real-world implications of the threshold changes.
The report notes that “For rare and ultra-rare diseases, NICE uses a cost-effectiveness threshold of £100,000 per quality-adjusted life year (QALY) gained. For very large health gains (e.g., >10 QALYs), this threshold can be adjusted upwards, potentially reaching £300,000 per QALY.”
Dan concluded: “We are always very supportive of any initiative that improves the life chances of people living with a rare disease.
“Families often struggle for years just to get a diagnosis, then all too often have to be told there is no effective treatment.
“If ways can be found to accelerate the process, and reduce the costs and complexities associated with rare disease drug approvals, then everyone benefits.”
