Mirella Marlow

The Health Technology Assessment of Companion Diagnostics: Experience of NICE

Companion diagnostics are used to aid clinical decision making to identify patients who are most likely to respond to treatment. They are becoming increasingly important as more new pharmaceuticals receive licensed indications that require the use of a companion diagnostic to identify the appropriate patient subgroup for treatment. These pharmaceuticals have proven benefit in the treatment of some cancers and other diseases, and also have potential to precisely tailor treatments to the individual in the future. However, the increasing use of companion diagnostics could place a substantial burden on health system resources to provide potentially high volumes of testing. This situation, in part, has led policy makers and Health Technology Assessment (HTA) bodies to review the policies and methods used to make reimbursement decisions for pharmaceuticals requiring companion diagnostics. The assessment of a pharmaceutical alongside the companion diagnostic used in the clinical trials may be relatively straightforward, although there are a number of challenges associated with assessing pharmaceuticals where a range of alternative companion diagnostics are available for use in routine clinical practice. The UK HTA body, the National Institute for Health and Care Excellence (NICE), has developed policy for considering companion diagnostics using its Technology Appraisal and Diagnostics Assessment Programs. Some HTA bodies in other countries have also adapted their policies and methods to accommodate the assessment of companion diagnostics. Here, we provide insight into the HTA of companion diagnostics for reimbursement decisions and how the associated challenges are being addressed, in particular by NICE. See all articles in this CCR Focus section, “The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development.” Clin Cancer Res; 20(6); 1469–76. ©2014 AACR.

Usefulness of a short-term register for health technology assessment where the evidence base is poor.

UNLABELLED This study reviews the coverage and usefulness of a short-term register, established specifically for health technology assessment of a novel interventional procedure (minimally invasive repair of pectus excavatum, or the Nuss procedure). METHODS Coverage of the register during 2004-07 was assessed by comparison with Hospital Episodes Statistics (HES) for England. Its usefulness was assessed by comparing safety and efficacy data with the published literature and by feedback from committee members who in 2009 were involved in reviewing NICEs original guidance from 2003. RESULTS The register reported 260 cases from thirteen UK hospitals during nearly 9 years. During a coverage evaluation period of 3 years, there were 152 registered Nuss procedures. An additional 246 repairs of pectus excavatum were undertaken in twenty-six previously unidentified hospitals. Of the 246, 23 were Nuss procedures (from two hospitals), 140 were open procedures (from eleven hospitals), and 3 were coding errors. No details were available for eighty cases undertaken at ten hospitals. The quantity of published literature had increased substantially since publication of original guidance in 2003. It related mostly to technical and safety outcomes, whereas the register included patient reported outcomes. The literature and the register reported similar rates of major adverse events such as bar displacement (2-10 percent). Committee members considered that the Register made a useful contribution to guidance development. CONCLUSIONS This study shows that a register set up to support a health technology assessment process can produce useful data both about safety and about patient-reported outcomes. Coverage may be improved by active follow-up based on routine hospital statistics. Improvement in coding for new procedures is needed in the United Kingdom.

A NEW HEALTH TECHNOLOGY ASSESSMENT SYSTEM FOR DEVICES: THE FIRST FIVE YEARS

OBJECTIVES The aim of this study was to review 5 years of activity from a new system devised by the National Institute for Health and Care Excellence (NICE), for assessing medical devices and diagnostics aimed at identifying and speeding adoption of technologies with clinical and cost advantages, compared with current practice in the United Kingdom healthcare system. METHODS All eligible notified technologies were classified using the Food and Drug Administration and Global Medical Device Nomenclature nomenclatures. Decisions about selecting technologies for full assessment to produce NICE recommendations were reviewed, along with the reasons given to companies for not selecting products. RESULTS Between 2009 and 2014, 186 technologies were notified (46 percent therapeutic and 54 percent diagnostic). Thirty-nine were judged ineligible (no regulatory approval), and 147 were considered by an independent committee. Of these, eighty (54 percent) were not selected for full assessment, most commonly because of insufficient evidence (86 percent): there were uncertainties specifically about benefits to the health service (54 percent), to patients (39 percent), and about cost (24 percent). The remaining 67 were selected and assessed for Medical Technology guidance (52 percent) (noninferior and/or lower cost consequences than current practice), for Diagnostics guidance (43 percent) or other NICE recommendations about adoption and use. Classifying technologies by two different systems showed no selection bias for any technology type or disease area. CONCLUSIONS Identifying new or under-used devices and diagnostics with potential benefits and promoting their adoption is important to health services in the United Kingdom and worldwide. This new system offers a means of fostering both uptake and further research. Lack of research data on new products is a major obstacle to evaluation.

How to improve the quality of evidence when new treatments are funded conditional on collecting evidence of effectiveness and safety.

Coverage with evidence development (CED) has been promoted as a means of providing early access to innovative technologies. The policy provides for funding of a treatment or technology conditional on gathering data through a clinical trial or registry designed to determine its effectiveness and to identify rare adverse events. CED has been used with varying degrees of success in the US, Switzerland, Canada and the UK, but the rigour of data collected has been a particular concern. Treatment registers have been criticized for their poor quality of data, particularly inadequate coverage and incompleteness. Inadequate coverage may lead to selection bias when patients who fit inclusion criteria for the register are missed. Incomplete data entry risks biased outcomes reporting. Both affect the reliability of the conclusions drawn. Randomized controlled trials (RCT) therefore continue to be considered the ‘gold standard’ in evidence-based medicine and are found at the summit of hierarchies of evidence, with observational studies in the foothills. However, RCTs have important limitations including uncertain generalizability and failure to identify important, rare safety concerns. Bradford Hill, the architect of the RCT stated: ‘Any belief that the controlled trial is the only way would mean not that the pendulum had swung too far but that it had come right off the hook’. Observational data give insight into realworld clinical practice and can be used by decision makers in health technology assessment (HTA). They could be a powerful tool for CED because they have the potential to reduce uncertainty around treatment costs, prevalence, safety, natural history and provider experience. Routine use of active surveillance would enhance the standing and usefulness of treatment register data and so increase their value in CED decision-making. Active surveillance is related to the approach taken by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) group which has provided reporting standards that aim to foster and improve quality in the use and production of observational studies. This is important work but is limited to describing problems which have occurred in the past and the ex post statistical methods to adjust for these failings (i.e. handling missing data and loss to follow-up). By contrast, active surveillance seeks to drive quality prospectively, rather than in retrospect. The active surveillance approach involves proactive monitoring of the quality and coverage of data submitted to a register, and regular communication with those submitting data, with a view to improving their quality. There are five important aspects of active surveillance:

Review of the role of NICE in promoting the adoption of innovative cardiac technologies

The National Institute for Health and Care Excellence (NICE) Medical Technologies Evaluation Programme (MTEP) promotes the adoption of innovative diagnostic and therapeutic technologies into National Health Service (NHS) clinical practice through the publication of guidance and briefing documents. Since the inception of the programme in 2009, there have been 7 medical technologiesguidance, 3 diagnostics guidance and 23 medtechinnovation briefing documents published that are relevant to the heart and circulation. Medical technologies guidance is published by NICE for selected single technologies if they offer plausible additional benefits to patients and the healthcare system. Diagnostic guidance is published for diagnostic technologies if they have the potential to improve health outcomes, but if their introduction may be associated with an increase in overall cost to the NHS. Medtechinnovation briefings provide evidence-based advice to those considering the implementation of new medical devices or diagnostic technologies. This review provides reference to all of the guidance and briefing medical technology documents that NICE has published that are relevant to the heart and circulation and reflect on their diverse recommendations. The interaction of MTEP with other NICE programmes is integral to its effectiveness and the means by which consistency is ensured across the different NICE programmes is described. The importance of the input of clinical experts from the cardiovascular professional community and the engagement by NICE with cardiovascular professional societies is highlighted as being fundamental to ensuring the quality of guidance outputs as well as to promoting their implementation and adoption.