Cost-effectiveness modeling often requires extrapolation of survival data from clinical trials over a long-term horizon. The choice of extrapolation method is often uncertain and can have a profound impact on the results. We propose a novel Bayesian approach towards incorporating external information (e.g., registry data or clinical opinion) into the extrapolation process as a means of reducing this uncertainty.

Standard parametric survival curves are fitted to immature time-to-event data using maximum likelihood estimation (MLE). Separately, external information on expected cohort-level survival at a future time point is used to specify a prior probability distribution. These are combined to generate posterior distributions of survival curve extrapolations that simultaneously incorporate both observed data and external information. This is done using importance sampling and multivariate normal approximations of the likelihood and posterior distributions; it requires only summary model parameter estimates (and not patient-level data). We apply our method to analyze survival data from the KEYNOTE-426 trial of pembrolizumab+axitinib in advanced renal cell carcinoma.

The method was implemented in R, and outputs survival curve parameters that are compatible with cost-effectiveness models developed in other software (e.g., Microsoft Excel). In all examples considered, our method resulted in extrapolated survival predictions that were more closely aligned with the external information compared with the standard (MLE-based) approach. Incorporation of external information decreased between-distribution variance (reduced structural uncertainty), and generally also decreased within-distribution variance as well (reduced parameter uncertainty). Results were comparable with those obtained from the method of Cooney and White, which uses similar ideas but requires full patient-level data and is more computationally complex.

The extrapolation method we describe can reduce uncertainty when valid external information is available. Only MLE-based parameter estimates are required to implement our method, thus secondary model users such as HTA agencies can adjust survival extrapolations from existing cost-effectiveness models without access to patient-level data. Implementation is straightforward and computationally efficient, and outputs are easily incorporated into existing cost-effectiveness models.

The National Centre for Pharmacoeconomics (NCPE) in Ireland conducts health technology assessments (HTAs) of drugs under consideration by the decision-maker for reimbursement. We analyzed how clinical expert opinion obtained by applicant pharmaceutical companies is used to inform HTA submissions made to the NCPE. We also describe how clinical opinion obtained by the NCPE is used to inform NCPE assessments.

We conducted a retrospective review of HTA submissions made to the NCPE from July 2019 to June 2020 inclusive. Data were extracted using a bespoke data collection instrument created in Microsoft Excel. To describe how clinical opinion informed the NCPE assessments, we extracted data from NCPE HTA Technical Summary Reports available on the NCPE website.

A total of 18 HTA submissions were reviewed. Clinical expert opinion was used by applicants to support all submissions. The median number of clinical experts who informed each individual HTA submission was seven (range 1 to 33); the majority were hospital physicians. Clinical opinion was used to inform HTA domains, including patient and population estimates (n=14; 78%), use of drugs in clinical practice (n=13; 78%), treatment effectiveness (n=6; 33%), healthcare resource use (n=14; 78%), and health-related quality of life (n=5; 28%). We present examples where clinical opinion, obtained by the NCPE, was used to inform NCPE assessments.

Clinical expert opinion informed all 18 applicant HTA submissions made to the NCPE during the study period. The NCPE also seeks clinical expert opinion to inform their assessments. Healthcare professionals make an important contribution to HTA and, thus, inform the decision-making processes on drug reimbursement in Ireland.

The National Centre for Pharmacoeconomics (NCPE) has a Patient Organisation Submission Process (POSP) enabling patients to communicate their experiences to the drug-reimbursement decision-maker. The NCPE proactively invites and supports patient organizations to make submissions to the decision-maker for ongoing health technology assessments (HTAs). We evaluate uptake of the POSP and determine whether submission trends differ by drug type.

We reviewed all HTAs completed by the NCPE since 2016 (when the POSP was first introduced) to present (data cut-off date 22 November 2023). Time trends in the proportions of HTAs for which a patient organization submission had been made to the NCPE were analyzed descriptively. We also compared the proportions of HTAs for which a patient organization submission had been made for (i) orphan versus non-orphan drugs and (ii) oncology versus non-oncology drugs.

The number of patient organization submissions made to the NCPE has increased over time. In 2016, 24 percent (6/25) of completed HTAs were associated with a patient organization submission compared with 50 percent (11/22) in 2023. The proportions of completed HTAs associated with a patient organization submission are comparable between orphan (38%; 24/64) and non-orphan drugs (29%; 34/117) (Chi²; p=0.245). The proportion of completed HTAs for which a patient organization submission had been made was lower for oncology drugs (14%; 14/97) versus non-oncology drugs (52%; 44/84) (Chi²; p<0.001).

Patient organization submissions to the NCPE have increased over time. The proportions of HTAs for which patient organization submissions have been made are comparable between orphan and non-orphan drugs. However, the proportion of patient organization submissions for oncology drugs is lower than the proportion for non-oncology drugs. The NCPE will continue to liaise with patient organizations to increase engagement with the POSP.