A review of NICE appraisals of pharmaceuticals 2000–2016 found variation in establishing comparative clinical effectiveness

Anderson, Michael; Naci, Huseyin; Morrison, Deborah; Osipenko, Leeza; Mossialos, Elías

doi:10.1016/j.jclinepi.2018.09.003

Cited by 26 publications

(23 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the absence of comparative data at the time of drug and device approval, many health technology assessment organisations and payers resort to using data with varying levels of limitations and uncertainty. 58 Current evidence standards may give patients and clinicians false reason for optimism that new treatments are beneficial and safe. 59,60 Clinicians and patients often overestimate the quality and quantity of evidence supporting new treatments.…”

Section: A Fragmented Evidence Base For Decision Making In Health Sysmentioning

confidence: 99%

Generating comparative evidence on new drugs and devices before approval

et al. 2020

Self Cite

View full text Add to dashboard Cite

Fewer than half of new drugs have data on their comparative benefits and harms against existing treatment options at the time of regulatory approval in Europe and the US. Even when activecomparator trials exist, they may not produce meaningful data to inform decisions in clinical practice and health policy. Recently, the uncertainty associated with the paucity of well-designed active-comparator trials has been compounded by legal and regulatory changes in Europe and the US that have created a complex mix of expedited programs aimed at facilitating faster access to new drugs. Comparative evidence generation is even sparser for medical devices. Some have argued that the current process for regulatory approval needs to generate more evidence that is useful for patients, clinicians, and payers in health care systems. We propose a set of 5 key principles relevant to the European Medicines Agency (EMA), European medical device regulatory agencies, and the US Food and Drug Administration (FDA), as well as payers, that we believe will provide the necessary incentives for pharmaceutical and device companies to generate comparative data on drugs and devices and assure timely availability of evidence that is useful for decision making. First, labeling should routinely inform patients and clinicians whether comparative data exist on new products. Second, regulators should be more selective in their use of programs that facilitate drug and device approvals on the basis of incomplete benefit and harm data. Third, regulators should encourage the conduct of randomised trials with active comparators. Fourth, regulators should use prospectively-designed network meta-analyses based on existing and future randomised trials. Fifth, payers should use their policy levers and negotiating power to incentivise the generation of comparative evidence on new and existing drugs and devices, for example, by explicitly considering proven added benefit in pricing and payment decisions.

show abstract

Section: A Fragmented Evidence Base For Decision Making In Health Sysmentioning

confidence: 99%

Generating comparative evidence on new drugs and devices before approval

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…via non-randomised studies) that requires appropriate methodologies that are not always taken into account. A review of NICE appraisals of pharmaceuticals (2000-16) by Anderson et al [148] found variations in establishing comparative clinical effectiveness. Of 489 individual pharmaceutical technologies assessed by NICE, 22 (4%) used non-RCT data to estimate comparative clinical effectiveness, with the methods for establishing external controls including: 13 (59%) used published trials, 6 (27%) used observational data, 2 (9%) used expert opinion and 1 (5%) used a responder vs non-responder analysis.…”

Section: Informing Decisions In Healthcare: a Discussion Related To Vmentioning

confidence: 99%

Conducting Value for Money Analyses for Non-randomised Interventional Studies Including Service Evaluations: An Educational Review with Recommendations

2020

View full text Add to dashboard Cite

This article provides an educational review covering the consideration of conducting 'value for money' analyses as part of non-randomised study designs including service evaluations. These evaluations represent a vehicle for producing evidence such as value for money of a care intervention or service delivery model. Decision makers including charities and local and national governing bodies often rely on evidence from non-randomised data and service evaluations to inform their resource allocation decision-making. However, as randomised data obtained from randomised controlled trials are considered the 'gold standard' for assessing causation, the use of this alternative vehicle for producing an evidence base requires careful consideration. We refer to value for money analyses, but reflect on methods associated with economic evaluations as a form of analysis used to inform resource allocation decision-making alongside a finite budget. Not all forms of value for money analysis are considered a full economic evaluation with implications for the information provided to decision makers. The type of value for money analysis to be conducted requires considerations such as the outcome(s) of interest, study design, statistical methods to control for confounding and bias, and how to quantify and describe uncertainty and opportunity costs to decision makers in any resulting value for money estimates. Service evaluations as vehicles for producing evidence present different challenges to analysts than what is commonly associated with research, randomised controlled trials and health technology appraisals, requiring specific study design and analytic considerations. This educational review describes and discusses these considerations, as overlooking them could affect the information provided to decision makers who may make an 'ill-informed' decision based on 'poor' or 'inaccurate' information with long-term implications. We make direct comparisons between randomised controlled trials relative to non-randomised data as vehicles for assessing causation; given 'gold standard' randomised controlled trials have limitations. Although we use UK-based decision makers as examples, we reflect on the needs of decision makers internationally for evidence-based decision-making specific to resource allocation. We make recommendations based on the experiences of the authors in the UK, reflecting on the wide variety of methods available, used as documented in the empirical literature. These methods may not have been fully considered relevant to non-randomised study designs and/or service evaluations, but could improve and aid the analysis conducted to inform the relevant value for money decision problem.

show abstract

“…Furthermore, in an unblinded trial, knowledge of treatment received can lead to bias in the reporting of outcomes. Methodological guidance is needed to deal with non-RCT evidence [26]. Guidelines on the circumstances in which the submission of non-RCT evidence is acceptable would also be helpful.…”

Section: Key Methodological Issuesmentioning

confidence: 99%

Pembrolizumab for Treating Relapsed or Refractory Classical Hodgkin Lymphoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

et al. 2019

View full text Add to dashboard Cite

As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Merck Sharp & Dohme; MSD) of pembrolizumab (Keytruda ® ) to submit evidence of its clinical and cost effectiveness for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma (RRcHL) who did not respond to treatment with brentuximab vedotin. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company’s submission to NICE. According to the NICE scope, pembrolizumab was compared with single or combination chemotherapy. Comparisons were undertaken in two populations: patients who did and did not receive prior autologous stem cell transplant (autoSCT; populations 1 and 2, respectively). Despite it having been recommended by NICE in population 1 at the time the ERG received the company submission, nivolumab was not included as a comparator. No studies directly comparing pembrolizumab and its comparators were identified. One ongoing, single-arm study of the efficacy and safety of pembrolizumab (KEYNOTE-087) and one comparative observational study (Cheah et al., 2016) were used to inform the comparative effectiveness of pembrolizumab and standard of care (SoC), using indirect comparisons in both populations. Almost all analyses showed significant PFS and overall response rate benefits for pembrolizumab versus SoC, but due to being based on indirect comparison, were likely to contain systematic error. The economic evaluation therefore suffered from substantial uncertainty in any estimates of cost effectiveness. Furthermore, there was a lack of evidence on the uptake and timing of allogeneic stem cell transplant, and alternative assumptions had a significant impact on cost effectiveness. Immature survival data from KEYNOTE-087 exacerbated this issue and necessitated the use of alternative data sources for longer-term extrapolation of survival. Some issues identified in the company’s analyses were amended by the ERG. The revised ERG deterministic base-case incremental cost-effectiveness ratios based on the company’s second Appraisal Consultation Document response for pembrolizumab versus SoC (with a commercial access agreement) for populations 1 and 2 were £54,325 and £62,527 per quality-adjusted life-year gained, respectively. There was substantial uncertainty around these ICERs, especially in population 2. NICE did not recommend pembrolizumab as an option for treating RRcHL in population 1, but recommended pembrolizumab for use within the Cancer Drugs Fund in population 2.

show abstract

A review of NICE appraisals of pharmaceuticals 2000–2016 found variation in establishing comparative clinical effectiveness

Cited by 26 publications

References 19 publications

Generating comparative evidence on new drugs and devices before approval

Generating comparative evidence on new drugs and devices before approval

Conducting Value for Money Analyses for Non-randomised Interventional Studies Including Service Evaluations: An Educational Review with Recommendations

Pembrolizumab for Treating Relapsed or Refractory Classical Hodgkin Lymphoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Contact Info

Product

Resources

About