Design of patient access schemes in the UK

Background

Patient Access Schemes (PAS) are alternative market access agreements between the UK Department of Health and drug manufacturers. They are implemented to enable the UK National Institute for Health and Clinical Excellence (NICE) to recommend expensive medicines for use in the UK NHS.

Objective

We aimed to analyse the extent to which NICE drug appraisals influence the construction of PAS and what rationale underlies the variety of approaches to their design.

Methods

We analysed publicly available documentation on PAS developed as a part of the NICE Health Technology Assessment process.

Results

We demonstrate how the design of PAS is determined by the kind of evidence that is available to model cost effectiveness of a drug and by the incremental cost-effectiveness ratio that is deemed acceptable in a given patient population. PAS aimed to reduce drug cost to the NHS by means of various discounts or rebates on a per-patient basis rather than by lowering the list price of drugs. While almost all schemes were proposed by the industry in reply to negative draft recommendations by NICE, motivations of the stakeholders to implement PAS are not disclosed in the publicly available documentation.

Conclusion

A more transparent process might be necessary to protect against a perverse impact of PAS on international reference pricing that uses list prices rather than the real cost of purchasing medicines that the NHS incurs.     

Cost-effective public health guidance: asking questions from the decision-maker's viewpoint

In February 2004, in his assessment of the long-term financial viability of the NHS, Derek Wanless recommended the use of 'a consistent framework, such as the methodology developed by NICE, to evaluate the cost-effectiveness of interventions and initiatives across health care and public health'. One year later public health was added to NICE's remit and the new National Institute for Health and Clinical Excellence (NICE) was established, with amended statutory instruments to permit consideration of broader public sector costs when developing cost-effective guidance for public health.With the principle of 'a consistent framework' put forward by Wanless as the starting point, this paper provides an insight into the most challenging aspects of applying the principles of cost-effectiveness analysis in the public health context from the policymaker's perspective. It reflects on the long-term consequences of taking on responsibility for producing public health guidance on the Institute's overall approach to guidance development and describes the tension between striving for consistency and cross-evaluation comparability while ensuring that the methodological tools used are fit for the purpose of developing public health guidance.     

Implications of the Appraisal Function of the National Institute for Clinical Excellence (NICE)

The National Institute of Clinical Excellence (NICE) has three main roles. It provides guidance to the National Health Service (NHS) on the use of selected new and existing technologies (the appraisal process), provides clinical guidelines for clinicians and physicians in important treatment areas, and develops audit methodologies. This paper discusses the NICE appraisal process. The specific steps of the appraisal process are described, including the basis for topic selection. An overview of NICE guidelines for manufacturers and sponsors is reported. First-year experience is assessed, reflecting on the quality of submitted evidence, and the content of the forthcoming program is presented. Finally, the impact of NICE appraisals is explored in terms of potential benefits and risks.     

"Yes", "No" or "Yes, but"? Multinomial modelling of NICE decision-making

The National Institute for Health and Clinical Excellence (NICE) issues mandatory guidance on health technologies to the UK NHS, based on clinical evidence, cost-effectiveness and other considerations. However, the exact factors considered, their relative importance and tradeoffs between them are not made explicit. Previous research modelled NICE decisions as a binary choice (accept/reject) dependent on cost-effectiveness, amongst other variables. This paper proposes and tests an alternative model of decision-making that may better represent the "yes, but..." nature of many NICE decisions. Decisions were categorised as "recommended for routine use", "recommended for restricted use" or "not recommended". The NICE appraisal process was modelled as a single decision between the three categories. Multinomial logistic regression techniques were used to evaluate the impact of: quantity/quality of clinical evidence; cost-effectiveness; decision date; existence of alternative treatments; budget impact; technology type. Results suggest that interventions supported by more randomised trials are more likely to be recommended and endorsed for routine use. Higher cost-effectiveness ratios increased the likelihood of interventions being rejected rather than recommended for restricted use but did not significantly affect the decision between routine and restricted use. Pharmaceuticals, interventions appraised early in the NICE programme and those with more systematic reviews were also less likely to be rejected, while patient group submissions made a recommendation for routine rather than restricted use more likely. The presence of factors affecting the decision between routine and restricted use but not that between routine use and rejection suggests that modelling these three outcomes reflects NICE decision-making more closely than binary-choice analyses.     

Evidence-informed evidence-making

The extent to which clinical and public health guidance developed by the National Institute for Health and Clinical Excellence (NICE) can effectively serve the public by improving quality and efficiency across the National Health Service (NHS) and the broader public sector depends largely on the quality and relevance of the available evidence which informs its decisions. There are well-established organizational and procedural links between NICE and academic and professional organizations that undertake evidence synthesis. However, there are fewer means for evidence gaps identified during the development of NICE guidance to lead to the commissioning of new prospective studies. In this paper, we discuss the importance of a publicly funded clinical and public health research agenda that includes new prospective studies aimed at addressing knowledge gaps identified by NICE. We describe the early experience of NICE and the National Institute for Health Research (NIHR) working together to articulate and commission research to inform best practice recommendations. We propose ways in which NICE can collaborate more effectively with research funders to improve the evidence base upon which it bases its recommendations.     

Meeting the NICE Requirements: A Markov Model Approach

The National Institute of Clinical Excellence (NICE) was established in the United Kingdom in April 1999 to issue guidance for the National Health Service (NHS) on the use of selective new health care interventions. This article describes the NICE requirements for both incidence-based cost-effectiveness analyses and prevalence-based estimates of the aggregate NHS impact of the new drug. The article demonstrates how both of these requirements can be met using Markov modeling techniques. A Markov model for a hypothetical new treatment for HIV infection is used as an illustration of how to generate the estimates that are required by NICE. The article concludes with a discussion of the difficulties of obtaining data of sufficient quality to include in the Markov model to ensure that the submission meets all the NICE requirements and is credible to the NICE advisory board.     

A Systematic Review of Economic Evaluations in Second and Later Lines of Therapy for the Treatment of Non-Small Cell Lung Cancer

Introduction

Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Surgery is generally accepted as the first-line treatment in patients with advanced/metastatic NSCLC, followed by radiotherapy and chemotherapy as second-line treatments. Docetaxel or erlotinib are generally recommended as the first-line chemotherapy option. The objective of this review was to identify previously published economic evaluations in NSCLC for second- and later-line treatments in order to (i) determine common modelling approaches and (ii) establish the relative cost effectiveness of these treatments. An overview of model critique was also produced to identify common criticisms from health technology assessment (HTA) bodies on the models submitted.

Methods

MEDLINE, Embase, EconLit, MEDLINE in Process^® and NHS Economic Evaluation Database (NHSEED) were searched (database start–October 2011), along with proceedings from eight major conferences (2007–2011). National Institute for Health and Clinical Excellence (NICE), Scottish Medicines Consortium (SMC), Pharmaceutical Benefits Advisory Committee (PBAC) and Canadian Agency for Drugs and Technologies in Health (CADTH) websites and the International Network of Agencies for Health Technology Assessment (INAHTA) database were also searched for appraisals in second- or later-line NSCLC. All published studies and HTA appraisals that reported economic evaluations of interventions used in current clinical practice as second- or later-line treatment in patients with advanced/metastatic NSCLC were included. Only studies in English were considered for inclusion. Studies which met the eligibility criteria after the screening of full-text articles were extracted by a reviewer and checked by a second party. Where multiple publications were identified describing a single study, the extracted data were compiled into one entry.

Results

A total of 29 studies were included which clearly evaluated second-line or later-line regimens. Most studies were either cost-effectiveness or cost-utility evaluations. Three-state transition Markov models were frequently used in cost-effectiveness and cost-utility evaluations. The model inputs were well reported and commonly consisted of data from pivotal trials. Sensitivity analyses were conducted in the majority of studies and covered variables such as cost, effectiveness, hospitalization and treatment duration. Therapies (docetaxel, pemetrexed and erlotinib) are for the most part cost-effective/cost-saving second-line therapies compared with best supportive care (BSC). Six erlotinib HTAs, across NICE, SMC, and PBAC, and four pemetrexed HTAs, one by NICE and three by SMC, were identified. The CADTH website did not provide sufficient detail on the appraisals and was excluded. Certain aspects of the models and model assumptions, e.g. efficacy inputs, were criticized or determined unjustifiable by the NICE, SMC and PBAC appraisal committees. Erlotinib and pemetrexed were considered to be cost effective versus docetaxel by NICE and SMC in the final submissions. PBAC considered erlotinib to be cost effective versus BSC following a price reduction in 2008.

Conclusion

Three-state Markov models are often used to conduct economic analysis in NSCLC and are regarded as appropriate to HTA agencies. Docetaxel, erlotinib and BSC are suitable comparators that should be considered for use in the model in the UK and Australia. Further, manufacturers should carefully select underlying assumptions used in the model, for both costs and clinical inputs, where the latter is derived from direct head-to-head trial data.     

Deliberating Tarceva: A case study of how British NHS managers decide whether to purchase a high-cost drug in the shadow of NICE guidance

This paper examines audio-recorded data from meetings in which NHS managers decide whether to fund high-cost drugs for individual patients. It investigates the work of a Welsh individual patient commissioning (IPC) panel responsible for sanctioning the purchase of 'un-commissioned' treatments for exceptional cases. The case study presented highlights the changing rationales used for approving or denying a cancer drug, Tarceva, during a period when NICE first suggested it was not cost effective, but then changed its position in a final technology appraisal recommending use when the cost did not exceed that of an alternative product. Our data show how decisions taken in the shadow of NICE guidance remain complex and subject to local discretion. Guidance that takes time to prepare, is released in stages, and relates to particular disease stages, must be interpreted in the context of particular cases. The case-based IPC panel discourse stands in tension with the standardised population-based recommendations in guidance. Panel members, who based their decisions on the central notions of 'efficacy' and 'exceptionality', often struggled to apply NICE information on cost-effectiveness to their deliberations on efficacy (clinical effectiveness). The case study suggests that the complex nature of decision making makes standardization of outcomes very difficult to achieve, so that local professional judgement is likely to remain central to health care rationing at this level.     

How should cost-effectiveness analysis be used in health technology coverage decisions? Evidence from the National Institute for Health and Clinical Excellence approach

BACKGROUND: In the National Health Service in England and Wales, technology coverage decisions are taken by the National Institute for Health and Clinical Excellence (NICE). The intention formally to apply cost-effectiveness analysis to the decision-making process distinguishes NICE from most other bodies making similar policy recommendations. We carried out a case study of the NICE Appraisals Committee to explore the influence and use of economic evaluation in the decision-making process. METHODS: Qualitative case study methodology. This involved analysis of all relevant secondary sources, observations of Appraisals Committee deliberations and interviews with a cross-section of Committee members. FINDINGS: Economic evaluation is integrated into the Committee's work. There are two main ways in which the use of economic analysis is understood by Committee members: an ordinal approach, whereby cost-effectiveness is only considered if the technology has passed a clinical effectiveness hurdle; and a framework approach, whereby the economic evaluation and model provide a structure for considering the decision problem and the evidence. These two approaches appear to operate simultaneously but are, in essence, inconsistent. CONCLUSIONS: The NICE 'experiment' has seen cost-effectiveness analysis move to the centre-ground of UK national policy deliberations regarding technology coverage. However, our case study implies that there may be room for further refinement of the appraisal process in order to resolve the observed tension between two different ways of incorporating cost-effectiveness analysis in NICE's decision-making.     

Regulating pharmaceutical markets: improving efficiency and controlling costs in the UK

UK government policy on pharmaceuticals is broadly integrated across the whole of health care policy. In the early 1990s, cost containment was emphasized, through budget holding by doctors to ensure clinical acceptability. From 2000 onwards, increased government funding for the NHS has allowed expansion of services and prescribing in areas of public health importance, but has been coupled with increased accountability and ambitious targets for the process of care and health outcomes. Standards for care are set in national guidelines including those from the National Institute for Clinical Excellence (NICE). NICE recommends or rejects new technologies to the NHS for their clinical value and cost effectiveness. Although following its advice is mandatory, evidence so far suggests that it has been only partly successful at improving services and eliminating variations. GP prescribing is monitored by Primary Care Organisations (PCO) which also hold the medicines budget. They may provide incentives to GPs for meeting targets in quality or expenditure. The UK government regulates the prices of generics but not of branded medicines; instead it regulates the profitability of the pharmaceutical industry. This arrangement seems to have been successful both at maintaining a major employer and export earner, and in limiting high drug expenditure.     

Increasing use of a new health technology during the wait for NICE guidance: findings from the third national tracker survey of photodynamic therapy

BACKGROUND: Photodynamic therapy (PDT) is a relatively new treatment for neovascular age-related macular degeneration. Trial evidence suggests that repeated treatments with PDT can decrease the relative risk of a reduction in visual acuity over 2 years. Concerns raised over the clinical and cost effectiveness of the treatment prompted a technology appraisal by the National Institute for Clinical Effectiveness (NICE). Difficulties in assessing the possible benefit or otherwise of PDT have led to delays in the publication of guidance. During this time the introduction of PDT into the UK National Health Service (NHS) has continued. Over three annual tracker surveys, we describe trends in the provision of PDT in the NHS and potential difficulties in the implementation of NICE guidance. METHODS: We undertook surveys in each October of 2000, 2001 and 2002 of clinical directors or lead consultants in all NHS eye units. These sought data on which (if any) patients were referred or treated with PDT and the thresholds of support for the use of PDT. RESULTS: Response rates were 82 per cent, 79 per cent and 82 per cent. The proportion of units routinely providing PDT for patients with more than 50 per cent classic sub-foveal CNV increased from 8.5 per cent in 2000 to 31 per cent in 2002 (p <0.001). Units referring or treating no patients decreased from 35 per cent to 10 per cent between 2000 and 2002 (p <0.001). There was a significant fall in the proportion of units changing policies on provision between 2000-2001 and 2001-2002. The proportion of respondents requiring further evidence before supporting the use of PDT decreased from 33 per cent in 2000 to 20 per cent in 2002. CONCLUSION: There is evidence of a continuing growth in access to PDT in the absence of NICE guidance. Although 90 per cent of units offer some pathway to treatment important variations in reported provision remain. Given that PDT services are becoming established, there is a risk that clinical policy is determined by local service development as much as by national guidance.     

The lag between effectiveness and cost-effectiveness evidence of new drugs

A new drug is approved for use if its efficacy and safety have been demonstrated. However, healthcare decision makers may also require data on the cost-effectiveness of new drugs if they are to make informed decisions about their place in therapy. Cost-effectiveness evidence may lag behind the effectiveness data in terms of its availability. We explored the timeliness of delivering cost-effectiveness information about new drugs with established effectiveness and significant financial impact. Drugs were identified, based on guidance documents and reports published by the UK National Institute for Clinical Excellence (NICE), and the following data were collected: dates of publication of first effectiveness and cost-effectiveness evidence, methodology of the cost-effectiveness analysis, quality scores of the clinical studies. Eighteen guidance documents on the use of new drugs/drug groups published by NICE by October 2001 covered 30 health technologies, which were included in the analysis. The analysis of the evidence showed that their effectiveness had been demonstrated in the last 12 years, with only two exceptions. However, cost-effectiveness evidence had been published for 21 (70%) of the technologies. The cost-effectiveness was estimated in 52.4% of cases using models. The good quality effectiveness evidence lagged behind the first effectiveness evidence by 1.40 years (95% CI 0.57–2.23), while the mean lag between the first effectiveness evidence and the first cost-effectiveness publications was estimated as 3.20 years (95% CI 1.76–4.65). Cost-effectiveness evidence thus often lags behind the effectiveness evidence. As a result healthcare decision makers are sometimes in a position of having to take decisions without having adequate cost-effectiveness data at their disposal.     

An illustration of the modelling of cost and efficacy data from a clinical trial

Health care providers, purchasers and policy makers need to make informed decisions regarding the provision of cost-effective care. When a new health care intervention is to be compared with the current standard, an economic evaluation alongside an evaluation of health benefits provides useful information for the decision making process. We consider the information on cost-effectiveness which arises from an individual clinical trial comparing the two interventions. Recent methods for conducting a cost-effectiveness analysis for a clinical trial have focused on the net benefit parameter. The net benefit parameter, a function of costs and health benefits, is positive if the new intervention is cost-effective compared with the standard. In this paper we describe frequentist and Bayesian approaches to cost-effectiveness analysis which have been suggested in the literature and apply them to data from a clinical trial comparing laparoscopic surgery with open mesh surgery for the repair of inguinal hernias. We extend the Bayesian model to allow the total cost to be divided into a number of different components. The advantages and disadvantages of the different approaches are discussed. In January 2001, NICE issued guidance on the type of surgery to be used for inguinal hernia repair. We discuss our example in the light of this information.     

National Institute for Clinical Excellence (NICE). HTA rhyme and reason?

The technology appraisal program of the National Institute for Clinical Excellence (NICE) was established on April 1, 1999. Its role is to advise the NHS in England and Wales on the clinical effectiveness, cost-effectiveness, and service impact of new and emerging as well as established healthcare technologies. This paper describes the role of HTA in the NICE technology appraisal process, discusses some of the challenges of the use of HTA in national policy making, and considers some of the potential ways forward.     

Omalizumab for the treatment of severe persistent allergic asthma in children aged 6-11 years

This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of omalizumab for the treatment of severe persistent asthma in children aged 6-11 years, based upon the evidence submission from Novartis Pharmaceutical UK Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The manufacturer's submission was generally considered to be of good quality. The submission was based primarily on a preplanned subgroup IA-05 EUP (European Union Population) from the IA-05 trial, with outcomes including the number of clinically significant (CS) and clinically significant severe (CSS) exacerbations. Omalizumab therapy was associated with a statistically significant reduction in the rate of CS exacerbations, but the reduction in the rate of CSS exacerbations was not statistically significant. The benefit in terms of CS exacerbations was achieved mainly in patients with more than three exacerbations per year at baseline. The manufacturer found no previous published cost-effectiveness studies of omalizumab in children aged 6-11 years, so their de novo economic evaluation formed the basis of the submitted economic evidence. The economic model was considered appropriate for the decision problem. The results from the model indicated that omalizumab in addition to standard therapy compared with standard therapy alone did not appear cost-effective in either the overall population or a subgroup of patients hospitalised in the year prior to enrollment, with incremental cost-effectiveness ratios of ￡ 91,169 and ￡ 65,911 per quality-adjusted life-year, respectively. These findings were found to be robust across a wide range of alternative assumptions through one-way sensitivity analyses. The guidance issued by NICE states that omalizumab is not recommended for the treatment of severe persistent allergic asthma in children aged 6-11 years.     

Comparing Patient Access to Pharmaceuticals in the UK and US

Background: The debate on access to new drugs has focused on the time lag between applications for approval and granting of marketing authorisation. This delay was identified as the first barrier with respect to patient access to new drugs, encompassing the hurdles of safety, efficacy and quality. Additional barriers have since been identified. These pertain to reimbursement and pricing of approved drugs, the so-called fourth and fifth hurdles. Methods: We reviewed 38 National Institute for Health and Clinical Excellence (NICE) guidance appraisals carried out between April 1999 and April 2005. These appraisals included 71 recently approved drugs considered to have either high clinical or cost impact. For each drug we first determined its marketing approval date by the British Medicines Healthcare Products Agency (MHRA) or European Medicines Evaluation Agency (EMEA). Secondly, we determined if each drug was approved by the US FDA for marketing and, if so, the date when it was approved. Thirdly, we considered whether and when each drug was recommended for reimbursement and use by NICE, and whether conditions of reimbursement applied. Fourthly, for the subset of FDA-approved drugs, we examined formulary placement, cost sharing and conditions of reimbursement on three-tier formularies used by seven leading US third-party payers serving Medicare beneficiaries. Fifthly, we reviewed each NICE recommendation to determine if cost-effectiveness data were referred to either in the appraisal documentation or in the final recommendation. Sixthly, we asked a spokesperson from each US payer whether cost-effectiveness assessments or rebates played a role in determining formulary placement of drugs in our sample, and whether there was a lag between marketing approval and reimbursement for any of the covered drugs. Results: Of the 71 drugs contained in 38 NICE guidance appraisals, the US FDA approved 64. On average, the subset of 64 drugs received marketing authorisation in the US prior to the UK. On average, US plans covered 87% of the 64 drugs, the same percentage of drugs recommended for NHS reimbursement and use. Cost sharing in the US was significantly higher than in the UK, with wider variation across plans. On average, drugs covered in the US had fewer conditions of reimbursement (15%) than the percentage of drugs given conditions by NICE (46%). US plans were quicker to decide to reimburse drugs following marketing approval than NICE. Conclusions: The US provides faster, more flexible access to most, but not all, of the UK-approved pharmaceuticals in our sample. However, US patients have higher cost sharing than the UK and coverage is less evenly spread across the population. From a policy perspective, our study findings confirm the need to bolster the NICE fast-track initiative to decrease the amount of time it takes to appraise certain new pharmaceuticals. Also, the study findings point to the need in the US for careful monitoring of plan compliance with regulations pertaining to the Medicare drug benefit, particularly with respect to formulary restrictions and limits on cost sharing.     

Who Does the Numbers? The Role of Third-Party Technology Assessment to Inform Health Systems' Decision-Making about the Funding of Health Technologies

Background:  There is an increasing number of health-care systems using economic evaluations to inform decisions about the reimbursement of health technologies. There are usually two separate elements of this process: assembling relevant evidence and undertaking analyses (technology assessment), and decision-making. In most systems, technology assessment is undertaken by the manufacturer of the technology. In a few, "third-party" assessment is used.
Methods:  In the United Kingdom, the National Institute for Health and Clinical Excellence used a combination of third-party and manufacturer assessments between 1999 and 2005. After this point, a Single Technology Appraisal program (using manufacturer-based assessment) was instituted for some technologies. Here the role of third-party assessment is considered in this from of decision-making. The article reviews the requirements of economic evaluation to support decision-making, and considers the extent to which each type of assessment is likely to meet these requirements. It also attempts to address whether the two forms of assessment differ in their impact on decision-making using a comparison of the decisions made by National Institute for Health and Clinical Excellence (NICE) (under its multiple-technology appraisal system) and the Scottish Medicines Consortium (SMC), which relies on manufacturer assessment.
Results:  The comparison is limited by the small number of technologies considered by both bodies. Nevertheless, it suggests that there are potentially important differences between the two bodies, with NICE generally placing more restrictions of the use of technologies.
Conclusions:  The article concludes that there are potential advantages to third-party assessment, but its cost and timing may preclude its use for all new technologies. A hybrid arrangement is suggested where third-party assessment is used in particular circumstances.     

Reallocating resources: how should the National Institute for Health and Clinical Excellence guide disinvestment efforts in the National Health Service?

The recent acute budgetary pressures within the English National Health Service (NHS) have accentuated calls for targeted disinvestment thereby eliminating ineffective or low-value services to provide resources that can be reallocated toward more cost-effective purposes. This challenge extends beyond allocating new resources wisely, a goal that has been, since its inception, the primary focus of the National Institute for Health and Clinical Excellence (NICE). But on 6 September 2006, the Department of Health announced a new mandate for NICE to help the NHS identify interventions that are not effective. This paper discusses current NICE efforts to support value in the NHS and then explores the policy options available to the Institute as it prepares to launch a programme to meet the NHS request for guidance on disinvestment. All of the possible options present challenges. NICE will need to collaborate in new ways with partners inside, and perhaps outside, the NHS. However, the Institute has an established reputation for rigour, transparency and political durability that makes it well qualified to sustain public support in the face of difficult decisions. Disinvestment will provide a stern test of these qualities.     

Working with NICE

The National Institute of Clinical Excellence (NICE) was set up by the Government as an independent health authority responsible for producing evidence-based public health and clinical guidance for the NHS in England, Wales and Northern Ireland. Guidance for Scotland is produced by the Scottish Intercollegiate Guidelines Network (SIGN). This article describes the workings of NICE and how health professionals and their professional organisations can influence the choice and content of guidelines. Health professionals should be aware of the guidance so they can contribute to it and use it in their own practice. They can use it to improve practice and even, at times, as a lever to protect endangered services from cutbacks.