28 Jun, 11 | by BMJ Group
A useful update was provided at a meeting this week sponsored by the Royal National Institute for the Blind (RNIB) and Patients Involved in NICE (the National Institute for Health and Clinical Excellence). As the proceedings are to be written up and published, I focus here on the key points that emerged for me.
The stakes in the Avastin/Lucentis (bevacizumab/ranibizumab) contest have been raised as the target condition has enlarged from macular degeneration to include diabetic macular oedema (DMO). This matters hugely because NICE is currently appraising Lucentis for this condition and has had to rule out consideration of Avastin because it is unlicensed. The potential patient population for DMO is put at 3% of people with diabetes, or around 100,000 patients each year. By contrast the estimates for wet age-related macular degeneration (AMD) are 20,000-25,000. NICE’s appraisal consultation does not recommend use of Lucentis for DMO. Avastin, it notes, is already being used off label to treat DMO in the NHS. This draft guidance, if it remains unchanged, will increase this use. By not recommending Lucentis for DMO, off-label Avastin will be the only option available. The draft guidance seems unlikely to change since the appraisal committee considered that “a model that relied on a combined set of plausible assumptions would be certain to produce ICERs [incremental cost-effectiveness ratios] that substantially exceed the range it could consider to represent an effective use of NHS resources” (para 4.26).
The meeting heard that Avastin is being widely used in the private sector to treat AMD. Some primary care trusts (PCTs) have offered patients the choice of immediate treatment in private clinics using Avastin or waiting for NHS treatment with Lucentis.
The reasons private clinics are using Avastin are unknown but plausibly relate to its price (£85 pre VAT per injection supplied by Moorfields pharmacy compared with £740 for Lucentis). Extraordinarily, it seems that some ophthalmologists may be using Avastin in private practice but, depending on the local PCT, they may be required to use Lucentis in their NHS practice. The extent to which NHS use is split between Avastin and Lucentis for AMD is unknown. However, a recent US study showed that 64% of all AMD Medicare patients received Avastin.
What is clear is that UK ophthalmologists are using Avastin off-label to treat AMD and DMO and that this use is likely to increase, particularly in DMO. Legally it was suggested that ophthalmologists are covered by their host NHS trusts via the NHS Litigation Authority. GPs, it was suggested, might not be so likely to do so, but GP commissioning groups might well be happy to contract for off-label use of Avastin by their providers.
In any legal challenge to off-label Avastin prescribing the guidance to doctors from the General Medical Council (GMC) would be hugely important. The meeting received an update on the GMC consultation on changing its 2008 guidance Good Practice in Prescribing Medicines. The consultation proposed to change the requirement that off-label prescribing be “better” to “as good as.” The 2008 guidance specified that the prescriber had to “be satisfied that it would better serve the patient’s needs than an appropriately licensed alternative.” The 2011 update proposed off-label prescribing if: “There was no appropriately licensed alternative available or you are satisfied on the basis of authoritative clinical guidance that is as safe and effective as an appropriately licensed alternative.”
The GMC , it appears, has been lobbied particularly by ophthalmologists on this issue and the consultation, the results of which are being analysed, seems likely to support change. Acceptance of the proposed change would require clarification of “authoritative clinical guidance”. Authoritative clinical guidance cited elsewhere by the GMC included that from NICE, royal colleges, the US Food and Drugs Agency (FDA), British National Formulary (BNF), or local prescribing committees. The meeting considered the possibility that a guideline, particularly if issued by a competent authority such as NICE, might also count.
Could a NICE guideline include off-label use of Avastin? Someone from NICE explained that although NICE cannot consider unlicensed drugs (or off-label use of licensed drugs) within the remit for technology appraisals, it can and has included such uses in its clinical guidelines. Almost all guidelines to do with children have to include off label use of licensed drugs. Which sparks the thought of what would happen if a NICE clinical guideline for either AMD or DMO included Avastin.
Could off-label Avastin be referred by the secretary of state for health to the Medicines and Healthcare products Regulatory Agency (MHRA) for “market approval”? Yes, is the answer, based on the precedent of such referrals of blood products and vaccines, which were noted at the meeting. NICE was asked if it could assess Avastin for AMD. The unsurprising answer was yes. “The next step is for the Department of Health to decide whether or not to refer bevacizumab (Avastin) to NICE for consideration as part of its technology appraisal process.” That was NICE’s view in December 2010.
I came away from the meeting thinking that the ophthalmologists are voting with their syringes and that some of the NHS is finding ways follow their lead.
James Raftery is a health economist with several decades’ experience of the NHS. He is professor of health technology assessment at Southampton University. A keen “NICE-watcher,” he has provided economic input to technical assessment reports for NICE but has never been a member of any of its committees. The opinions expressed here are his personal views. Comments welcomed.