In the lead up to our R&D Conference on 20 November, one of our speakers, Adrian Towse, Director of the Office of Health Economics (OHE), writes a guest blog about the benefits and challenges of diagnostic testing.
Greater use of stratified medicine – targeting treatments at particular patient groups we know are going to benefit – depends on the use of diagnostic tests of varying degrees of complexity.
An increasing number of new medicines are aimed at a small patient group where the benefits are known to be high. Ensuring the drug gets to patients that can benefit and not to those that can’t is essential. One example is Xalkori (crizotinib) for non small cell lung cancer (NSCLC). It is effective against metastatic NSCLC caused by a defect in the ALK gene. Only around three per cent to five per cent of people with NSCLC may test positive for the ALK fusion gene and so can benefit from the treatment.
Herceptin (trastuzumab) was the first new medicine in this category. It is a highly effective treatment for breast cancer, but only for women who express the HER2 positive protein. Around 25 per cent of patients are HER2 positive. For the NHS to get value and patients to benefit, only patients testing HER2 positive should take the drug, and all women who are HER2 positive. This requires accurate testing, and the agreed international protocol is for a two stage process, whereby a second, different type of test, is carried out on patients for whom it is not clear from the results of the first test if they qualify for the drug.
The National Institute for Health and Care Excellence (NICE) already has experience of Technology Appraisals of new medicines in which there needs to be a test taken to decide if the patient is eligible for treatment. This process works well, although, whilst NICE regards the ’companion diagnostic’ as covered by the funding mandate for the Technology Appraisal, it is not clear that the NHS recognises this.
Diagnostic tests vary in their accuracy. Better tests – with improved accuracy – bring the potential for more health gain and for lower treatment costs per truly positive patients. These tests can therefore be cost effective for the NHS, even at higher acquisition prices. NICE has a Diagnostic Assessment Programme (DAP) to review these tests to see if they provide value for money. It uses a cost-per-QALY framework. The clinical utility or value of a test comes from using the test in combination with a change in clinical practice (such as prescribing a different medicine depending on the result of the test) to produce a better health outcome for the patient, as compared to using a different test or not testing at all. The DAP programme places NICE as a world leader in applying value-for-money principles to diagnostics through a Health Technology Assessment programme that looks at the cost effectiveness of using better diagnostic tests to improve the health of NHS patients.
However, there are challenges. I set out four. Firstly, there may be several tests available of different accuracy and cost to help target a new medicine. The Technology Appraisal Committee may need the expertise of the DAP members to help them assess the right test to recommend for use with the new drug. Secondly, not all important aspects of a test may be captured in the cost effectiveness framework. Research evidence suggests that patients value test information even when it does not change treatment options – there is a value of knowing. Thirdly, the evidence of clinical utility (or value) for most tests is very poor, unless they have been included in clinical trials by the drug manufacturer. It may be that the NICE DAP needs to encourage evidence collection alongside use of the test, in order to clarify whether tests are, when used in routine clinical practice, as good as the early indications of performance suggest. Fourthly, there is no funding mandate for NICE DAP approved tests. NICE approved Oncotype Dx, a test for the likelihood of breast cancer recurrence, to help clinicians and their patients decide whether or not to use chemotherapy after surgery. It delivered better health (by avoiding the side effects of chemotherapy that was unlikely to be of benefit) and saved drug treatment costs. It was cost effective even though the price of the test pushed up NHS costs, because of the health benefits that it delivered. NHS England decided not to pay for it on budget impact grounds.
NICE and the NHS have the opportunity to lead the introduction of cost-effective stratified medicine into the NHS, benefiting patients and establishing the UK as the place to undertake research and to collect evidence of clinical utility. For it to do so, these challenges must be overcome.
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Director of the Office of Health Economics