Assessment of quality of data submitted for NICE technology appraisals over two decades.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) pioneered the Health Technology Assessment (HTA) processes and methodologies. Technology appraisals (TAs) focus on pharmaceutical products and clinical and economic data, which are presented by the product manufacturers to the NICE appraisal committee for decision-making. Uncertainty in data reduces the chance of a positive outcome from the HTA process or requires a higher discount. OBJECTIVE: To investigate the quality of clinical data (comparator, quality of life (QoL), randomised controlled trials (RCTs) and overall quality of evidence) submitted by the manufacturers to NICE. DESIGN: This retrospective evaluation analysed active TAs published between 2000 and 2019 (up to TA600). METHODS: For all TAs, we extracted data from the Assessment Group and Evidence Review Group reports and Final Appraisal Determinations on (1) the quality of submitted RCTs and (2) the overall quality of evidence submitted for decision-making. For single TAs, we also extracted data and its critique on QoL and comparators. Each category was scored for quality and analysed using descriptive statistics. RESULTS: 409 TAs were analysed (multiple technology appraisals (MTA)=104, single technology appraisal (STA)=305). In two-thirds of TAs, the overall quality of evidence was either poor (n=224, 55%) or unacceptable (n=41, 10%). In 39% (n=119) of the STAs, the quality of comparative evidence was considered poor, and in 17% (n=51) unacceptable. In 44% (n=135) of STAs, the quality of QoL data was considered poor, 15% (n=47) unacceptable, 33% (n=102) acceptable and 7% (n=21) as good. Over 20 years of longitudinal analysis did not show improvements in the quality of evidence submitted to NICE. CONCLUSION: We found that the primary components of clinical evidence influencing NICE's decision-making framework were of poor quality. It is essential to continue to generate robust clinical data for premarket and postmarket introduction of medicines into clinical practice to ensure they deliver benefits to patients.

The Origin of First-in-Class Drugs: Innovation Versus Clinical Benefit.

First-in-class (FIC) designation became a hallmark of innovation, however, even at the marketing authorization stage, little is known about the clinical benefits these products deliver. We identified the provenance of the FIC drugs that entered the French market from 2008 to 2018 and matched these medicines to the clinical benefit grading by Haute Autorité de Santé (HAS) and Prescrire. Analyses were performed using descriptive statistics to present our findings by drug origin and therapeutic area and to establish the degree of concordance between HAS and Prescrire. Of the 135 FIC drugs identified, 71.1% (n = 96) originated from the industry, 16.3% (n = 22) from academia, and 12.6% (n = 17) from joint partnerships. Three therapeutic areas accounted for most FIC medications: antineoplastic (25.9%, N = 35), anti-infective (14.1%, N = 19), and metabolic (11.1%, N = 15) agents. HAS and Prescrire agreed on 60.74% of clinical benefit gradings. According to HAS, only 5% of all FIC drugs had substantial added benefit, and only 3%, according to Prescrire. HAS and Prescrire graded 45.9% and 68.2%, respectively, of FIC drugs as no clinical benefit and 48.9% and 28.9%, respectively, as some clinical benefit. FIC-designated drugs are primarily of industry (> 70%) rather than academic origin. We found that 55% of FIC medicines that entered the French market over the 10-year period deliver no additional clinical benefit. Whereas FIC medicines may represent important scientific advancements in drug development, in > 50% of cases, the new mode of action does not translate into additional clinical benefits for patients.