NICE in the dock: what the judicial review means for pharma

pharmafile | April 16, 2007 | Feature | Research and Development, Sales and Marketing |  NICE, UK, healthcare, judicial review 

The National Institute for Health and Clinical Excellence (NICE) has been at the centre of controversy ever since its inception in 1999, but now, its work and its authority are being more hotly contested than at any other time in its short history.

Currently, there are two major inquiries pending in relation to NICE; the first, a judicial review, has arisen as a direct result of guidance contained in a Final Appraisal Document (FAD) whereby Alzheimer's drugs are to be withheld to certain groups of patients. The second is an inquiry to be carried out by the Commons Health Select Committee, which will be examining aspects of NICE's work, the reasons for attacks on its decisions and the level of public confidence in the institute.

In particular, the select committee is to examine NICE's evaluation process and whether any disadvantage is suffered by groups as a result of the process. The implementation of NICE guidance, both technology appraisals and clinical guidelines, as well as the appeal system, are included within the inquiry's remit.

Written submissions to the select committee have now been made, and the Alzheimer's Society and Pfizer, which co-markets the Alzheimer's drug, Aricept (donepezil), with Eisai, have both welcomed the inquiry and are likely to make submissions to the judicial review.  

NICE accused

The background to this investigation is the long-running row over access to Alzheimer's medicines. In 2001, NICE recommended drug therapy for patients with both mild and moderate Alzheimer's disease, but after a long process, NICE effectively reversed this decision for some patients in November 2006.

The guidance, if followed, means that newly-diagnosed patients with mild Alzheimer's are unlikely to be prescribed drugs, such as Aricept, which were previously available on the NHS.  Sufferers who are in either the early or late stages of the disease would be the ones to be affected by the agency's ruling, which it says, is based on the lack of evidence of the drug's efficacy in these patients This decision has been widely condemned by patient groups, including the Alzheimer's Society.

In January this year, Eisai, the licence-holder of Aricept, and Pfizer applied to the High Court for permission to request a judicial review of the process by which NICE ruled that some patients with Alzheimer's disease should no longer receive drug treatment. This is the first legal challenge of this nature to a NICE decision and the judicial review, which was granted in March, will look at the process by which NICE developed guidance on the use of drugs for treating Alzheimer's disease.

The key area of concern arising from NICE's evaluation methods in this particular case, is their use of a computer model to assess assumptions about price and effectiveness of treatment. This model has not been made available for scrutiny meaning that stakeholders are unable to assess the efficacy of NICE's clinical or economic assessment of a product.

Before issuing its application for leave for judicial review, Eisai called on NICE to withdraw its FAD, and requested disclosure of a fully transparent working version of the model used in the calculation of cost-effectiveness. Eisai asked NICE to develop a new FAD using rational clinical assumptions and both a more accurate cost-effectiveness model and data  essentially a call for transparency in this aspect of NICE's deliberations.  

The institute answers back

In its response, NICE's chief executive, Andrew Dillon commented that the institute's methodology and process for evaluating medicines has been assessed by the World Health Organisation to be of the highest standard and the board has full confidence in the conduct of the appraisal of the Alzheimer's drugs.

He went on to say he considered NICE's consultation, decision-making and appeals processes to be transparent and fair, adding: "We share our methodology and enable our stakeholders to see the basis on which our experts arrive at their decisions. We invite patients, medical professionals and anyone who has an interest to express their views and comment on our proposals."  

A previous Commons Health Committee report in 2002 recommended that NICE improve its transparency by communicating to stakeholders as clearly as possible how and why it arrived at its decisions. It also called for all information used by NICE in its decision-making to be made available for public scrutiny, as well as greater clarity over the criteria for evaluating clinical and cost-effectiveness.

Since this report, there have been many developments and innovations to NICE's technology appraisals. Its Guide to the Technology Appraisal Process is supplemented by its Guide to the Methods of Technology Appraisal, which provides an overview of principles used and how stakeholders can contribute and what is required of them.  

Why a judicial review?

So, what will the various parties be hoping to achieve from the judicial review? A judicial review is the process by which the High Court controls the exercise of powers by public bodies. The courts have an inherent jurisdiction to review the way those entrusted with the performance of public duties carry out their functions, where this affects those with legally recognised interests. A court charged with the task of judicial review will not look at the merits of a decision itself – this is not the court's function in such proceedings. So, it will not be NICE's FAD and its conclusions that will be reviewed, but rather the decision-making process itself.  

In a judicial review, the court will examine whether a public body has exceeded its powers or, in this particular case, whether a decision-maker has failed to observe the principles of natural justice or procedural propriety, by way of a failure to provide a fair and transparent process. A decision may also be reviewed because it is one which no reasonable agency or tribunal could have reached or because the decision-making body has abused its powers.  

There are a number of bases for judicial review. Broadly, these grounds are classified under the headings of illegality, irrationality and procedural impropriety. It has been recognised that these criteria are capable of expansion and one area where this has occurred is by reference to the Human Rights Act 1998, which incorporated the Convention for the Protection of Human Rights and Fundamental Freedoms.  This may be viewed either as a new ground of challenge or as a specific example of illegality.

Since NICE has refused to disclose a fully working version of the cost-effectiveness model used to determine the value of treatment in patients with mild Alzheimer's disease, Eisai and Pfizer have stated that they believe the process leading to the FAD and new treatment guidance was unfair. They consider that many of the conclusions drawn in the FAD cannot be supported legally and/or are irrational.

In addition to seeking a judicial review on the grounds of procedural unfairness and irrationality, the companies also allege that the use of a rigid diagnostic tool – in this case, mini mental state examination scores – discriminated against certain patient groups. It could, therefore, be argued that NICE has acted in breach of a convention right, conferred by way of the Human Rights Act 1998.  

A question of fairness

At the heart of the judicial review is the question of fairness and transparency in NICE's decision-making process. However, the importance of natural justice considerations, such as fairness and transparency, will be very difficult for the court to weigh and apply.

Legally interested parties to NICE's FAD in respect of Alzheimer's treatments, should be able to see what matters have been taken into consideration and what view was formed by NICE on the points which arose. However, there is no uniform standard of reasoning which is required. Questions of the sufficiency, accuracy and rationality of the decision will turn on the issue and circumstances arising in a particular case.

The concept of fairness is inevitably difficult to define and the requirements which it will impose will depend upon all the circumstances linked to the prescription of Alzheimer's drug therapies.

The duty to act fairly will have to be considered by reference to a number of factors, including the subject matter of the decision, the interest of those bringing the review and the impact of the government body's decision upon them, as well as the finality of the decision and the right of appeal. Where reasons have been given for a decision, the evidence must show the existence of reasons consistent with the findings and the decision. However, the link between procedural fairness and the substance of the decision arrived at by the decision-making body remains difficult for the courts to pinpoint.

The technology appraisal process is designed to include a systematic and independent evaluation of relevant evidence available in relation to a product. The aim is to produce an estimate of its clinical and cost-effectiveness for a specific indication. The appraisal part of the process is designed to consider the conclusions of the assessment stage along with additional information supplied by consultees, commentators, clinical specialists and patient experts. NICE consider technologies to be clinically effective if they confer an overall health benefit, taking account of any harmful effects, when compared with relevant alternatives.

The general consequences for the wider group of patients in the NHS are considered alongside the benefits for those patients who are directly affected by the particular technology.  

The courts considerations

When it comes to appraising cost-effectiveness, NICE's judgments are stated to be influenced by the following factors: strength of the supporting clinical effectiveness evidence; the robustness of the structure and the plausibility of the assumptions made in the economic model; the Appraisal Committee's preferred modelling approach, taking into account all the economic evidence submitted and the critique of the manufacturer's models; and the range and plausibility of the incremental cost-effectiveness ratios generated by the models reviewed.

Against this framework, the court will need to consider whether the assumptions made or the conclusions drawn in the FAD are rational and can be supported. The manufacturers will argue that without being able to consider a transparent working version of the cost-effectiveness model, they have been unable to consider or respond to the arguments being relied upon by NICE as part of the process leading to the FAD.  

The court will also need to consider whether there has been a breach of article 14 of the Human Rights Convention, which prohibits discrimination on any ground. For there to be a breach of this article, the area in which a person is discriminated against has to come within the scope of one of the other convention articles.

It is unlawful for a pubic authority to act in a way which is incompatible with the rights conferred under the convention, but this, too, will be a matter for considerable debate before the courts, bearing in mind the wide-ranging and ever-changing criteria NICE must apply in giving guidance to the NHS on the health benefits and costs of new technologies.

Clarity and transparency

Now permission for the judicial review has been granted, the defendant must set out detailed grounds for contesting the claim, along with any written evidence upon which it intends to rely. The court will provide directions for the future management of such a claim, leading to an eventual hearing. By this time, the criticisms facing NICE are likely to have been well rehearsed by both patient groups and before the select committee.  

Speaking for the wider UK pharma industry, earlier this year, Director General of the ABPI Dr Richard Barker commented: "Public and patients have been dismayed by recent NICE decisions covering a wide variety of medicines that effectively deny patients in England and Wales access to therapies available elsewhere.

NICE has an essential, if unenviable, role to play in defining priorities and setting standards of care –  which makes it vital that it stands for clinical excellence and that the thinking behind this decision-making is clear to all.  

The ABPI indicated that it believed NICE was applying arbitrary thresholds of cost-effectiveness. This lack of transparency was noted as a cause for concern by the Commons Health Committee in 2002. Despite the progress made by NICE in its appraisal processes, it is regrettable for all parties concerned – patients, manufacturers and NICE – that a further consideration of this issue has become necessary; but the need for transparency is such that scrutiny at the highest levels was inevitable.

The judicial review, in tandem with the health select committee, has the potential to bring about significant change in the NICE process. The industry could certainly benefit if NICE is forced to make public its economic modelling, as this would allow pharma to better understand just what is required to gain a NICE recommendation.

Nevertheless, such a move could not eliminate NICE's raison detre, which is to demand proof of the cost and clinical effectiveness of new medicines – a process which is fundamentally contentious and frequently controversial.

How would an adverse decision affect NICE?

The High Court has now agreed that there should be a judicial review of NICE's decision in respect of the  Alzheimer's drugs.

But what are the potential end results of the review for NICE, patients and the industry?

It must be remembered that the court will not substitute its own view for that of NICE. The court will only exercise a supervisory role, examining the decision-making process itself, rather than ruling what the decision should have been.

The remedy likely to be granted by the court will be what is called a declaration, setting out its findings on the questions before it. While the strict legal remedy that can be offered by the court is therefore limited, any adverse finding would be a serious blow to NICE and to its standing, both within the industry and before the glare of public and media scrutiny.

A court decision is likely to concentrate solely on the decision-making process behind this specific drug, but any criticism of NICE will be seen as a victory for the challengers and is likely to result in the restriction on funding of Alzheimer's drugs being lifted.

However, the repercussions could go a lot further, instigating a review of NICE's consultation process, its transparency and the factors it takes into account when weighing evidence and arriving at decisions.

It is unlikely that a court decision will be returned quickly  and even then, there is always the possibility of either party appealing the decision.

But these proceedings, along with the Health Select Committees inquiry, are adding to the pressure for NICE to make radical changes to the way it works.

Alison McAdams, Associate Partner at Davies Arnold Cooper.

For more information contact Davies Arnold Cooper on tel: 020 7936 2222