Improving production times for guidance on new pharmaceuticals

One of NICE?s regular functions is to produce recommendations on the use of new and existing medicines and treatments in the NHS.

One of NICE's regular functions is to produce recommendations on the use of new and existing medicines and treatments in the NHS.

The NICE technology appraisals programme is responsible for this area of work. It produces guidance on pharmaceuticals through the single technology appraisals (STA) process, which appraises a single product with a single indication, based on the best available evidence.

Once a new drug has been licensed for use in the UK by regulatory authorities, NICE aims to produce guidance on whether the drug is cost and clinically effective.

Since our formation in 1999, one of the most common criticisms of NICE is that we have been too slow in developing our recommendations on the use of drugs in the NHS.

This is despite the fact that the length that NICE takes to appraise a drug has reduced dramatically over time, and continues to do so.

Recently, NICE published final guidance on use of apixaban for the prevention of stroke in patients with atrial fibrillation. The guidance comes a mere four months after the drug was initially licensed.

The process this drug went through, from referral to NICE, to licensing, and final publication of guidance, is an example of how the NICE appraisal process is timely and effective when it comes to drugs that are referred with appropriate evidence on their cost and clinical effectiveness.

How the guidance process works

The process for appraising begins once a drug has been formally referred to NICE by the Secretary of State for Health.

For apixaban, one reason why final guidance was produced so quickly is because it was referred before the drug received a licence for use in the UK from regulatory authorities.

Apixaban was referred to NICE in November 2011, and received its licence for use in November 2012. By this stage, NICE was already well on its way towards the production of final guidance.

Jenniffer Alty, Associate Director of Planning and Operations for Appraisals at NICE's Centre for Health Technology Evaluation, says: "NICE liaises with pharmaceutical companies with regards to anticipated license timings. In most cases, as with apixaban, the process for appraisal will begin before the drug receives its official licence.

"If for any reason a drug does not receive a licence for use, then we cannot continue with the production of guidance for the drug."

Before any appraisal is formally referred, NICE develops a draft scope for its use. For apixaban, the scope covered adults with atrial fibrillation - a condition that causes the heart to beat irregularly - and who are at moderate to high risk of stroke or systemic embolism.

The manufacturer was then asked to provide a submission of evidence which was considered by an external academic organisation independent of NICE, called the Evidence Review Group (ERG). This process occurs with every STA.

In certain cases, the evidence submission might be incomplete, or might not refer appropriately to the final scope. If this happens, then NICE will consult with the independent group, request a meeting with the manufacturer, and inform all of the delay in timelines.

However, in the case of apixaban there were no issues with the evidence submitted, and so the ERG could proceed straight towards preparing a report.

Ms Alty says: "The ERG critiqued the evidence submitted by the manufacturer.

"NICE then compiled an evaluation report containing information from the manufacturer's submission, and the report from the ERG. All of this was passed on to our Appraisals Committee."

Publishing final guidance

The Appraisal Committee is an independent advisory body which considers all submitted evidence and has clarification provided from nominated clinical specialists, patient experts, manufacturer representatives and NHS commissioning experts.

At this stage, the committee might decide that an appraisal consultation document (ACD) should be produced. This can happen if the manufacturer or sponsor needs to provide further clarification on the evidence submitted, or if the recommendations limit use of the product further than it is licenced for.

Once an ACD is produced, it is put out for a four-week consultation, after which the Appraisal Committee meets again to consider comments.

However, for apixaban the committee decided that an ACD was not needed, so the recommendations could go straight to a final appraisals determination (FAD). This document contains final recommendations from NICE on how the technology should be used in the NHS in England and Wales.

Since NICE received no appeals on the FAD for apixaban, the final guidance was published on the NICE website on February 2013.

Ms Alty says: "We have now published 17 STAs that have gone straight to a FAD. For apixaban, the committee felt the evidence was clear-cut, and no further clarification was needed.

"This, together with no appeals received, helped speed up the process for the production of final guidance from NICE."

More information on the process that is gone through to produce STAs, and the methods behind then is available in the guides NICE has produced on technology appraisals.

NICE's final guidance on apixaban (Eliquis), recommends the drug in accordance with its licensed indications, as an option for the prevention of stroke and systemic embolism in some people with non-valvular atrial fibrillation.

The guidance means that drug can be used an alternative to anticoagulants such as warfarin, which can be inconvenient and uncomfortable to use.

NICE says any decision to start treatment should be made after an informed discussion between the clinician and the patient about its risks and benefits compared with warfarin, dabigatran, etexilate and rivaroxaban.