Value of External Data in the Extrapolation of Survival Data: A Study Using the NJR Data Set.

BACKGROUND: Extrapolation of time-to-event data can be a critical component of cost-effectiveness analysis. OBJECTIVES: To contrast the value of external data on treatment effects as a selection aid in model fitting to the clinical data or for the direct extrapolation of survival. METHODS: We assume the existence of external summary data on both treatment and control and consider two scenarios: availability of external individual patient data (IPD) on the control only and an absence of external IPD. We describe how the summary data can be used to extrapolate survival or to assess the plausibility of extrapolations of the clinical data. We assess the merit of either approach using a comparison of cemented and cementless total hip replacement as a case study. Merit is judged by comparing incremental net benefit (INB) obtained in scenarios with incomplete IPD with that derived from modeling external IPD on both treatment and control. RESULTS: Measures of fit with the external summary data did not identify survival model specifications that best estimated INB. Addition of external IPD for the control only did not improve estimates of INB. Extrapolation of survival using the external summary data comparing treatment and control improved estimates of INB. CONCLUSIONS: Our case study indicates that summary data comparing treatment and control are more valuable than IPD limited to the control when extrapolating event rates for cost-effectiveness analysis. These data are best exploited in direct extrapolation of event rates rather than as an aid to select extrapolations on the basis of the clinical data.

Anticipated effects of burosumab treatment on long-term clinical sequelae in XLH: expert perspectives.

X-linked hypophosphatemia (XLH) is a rare, progressive, genetic disease with multisystem impact that typically begins to manifest in early childhood. Two treatment options exist: oral phosphate in combination with active vitamin D ("conventional therapy") and a fully human monoclonal anti-FGF23 antibody, burosumab. The clinical benefit of conventional therapy in adults is limited, and poor tolerance and complications are common. Burosumab was first approved as a treatment for XLH in 2018 and its disease-modifying benefits in clinical trials in children suggest burosumab treatment could also alter the disease course in adults. Without long-term clinical data on multiple XLH-related sequelae available, the results of an elicitation exercise are reported, in which eight global experts in XLH posited how long-term treatment with burosumab is anticipated to impact the life course of clinical sequelae in adults with XLH. Based on their clinical experiences, the available evidence and their disease understanding, the experts agreed that some long-term benefits of using burosumab are likely in adults with XLH even if they have a misaligned skeleton from childhood. Burosumab treatment is anticipated to reduce the incidence of fractures and halt the progression of clinical sequelae associated with conventional therapy. While the trajectories for established dental abscesses are not expected to improve with burosumab treatment, dental abscess development may be prevented. Starting treatment with burosumab in childhood to increase the likelihood of an aligned skeleton and continuation into and throughout adulthood to maintain euphosphatemia may optimize patient outcomes, although future real-world investigation is required to support this hypothesis.