Incorporating external trial data to improve survival extrapolations: a pilot study of the COU-AA-301 trial

Survival extrapolation plays a key role within cost effectiveness analysis and is often subject to substantial uncertainty. Use of external data to improve extrapolations has been identified as a key research priority. We present findings from a pilot study using data from the COU-AA-301 trial of abiraterone acetate for metastatic castration-resistant prostate cancer, to explore how external trial data may be incorporated into survival extrapolations. External trial data were identified via a targeted search of technology assessment reports. Four methods using external data were compared to simple parametric models (SPMs): informal reference to external data to select appropriate SPMs, piecewise models with, and without, hazard ratio adjustment, and Bayesian models fitted with a prior on the shape parameter(s). Survival and hazard plots were compared, and summary metrics (point estimate accuracy and restricted mean survival time) were calculated. Without consideration of external data, several SPMs may have been selected as the ‘best-fitting’ model. The range of survival probability estimates was generally reduced when external data were included in model estimation, and external hazard plots aided model selection. Different methods yielded varied results, even with the same data source, highlighting potential issues when integrating external trial data within model estimation. By using external trial data, the most (in)appropriate models may be more easily identified. However, benefits of using external data are contingent upon their applicability to the research question, and the choice of method can have a large impact on extrapolations.

Four points regarding reproducibility and external statistical validity: a comment on Walter et al.

Walter et al. (2021) present phase 1–2–3 trial data that show two doses of the BNT162b2 (Pfizer–BioN-Tech) Covid-19 vaccine were safe and effective in children aged 5–11 years. Given that millions of children in this age group are receiving the paediatric Pfizer COVID-19 vaccine, that there are potential risks, and that the balance of benefits over potential risks is more limited in children compared to adults due to low rates of serious disease (ATAGI 2021), gold standards ought to be applied to supporting data in terms of placebo-controlled disease endpoint efficacy trials, safety databases large enough to detect adverse events, and appropriate data sharing to enable reproduction and scrutiny of results. Four points are worthy of attention regarding the reproducibility and external statistical validity of the analysis reported in Walter et al. (2021). ‘External validity’ refers to the extent to which conclusions drawn from the data (and statistical tests thereof) are likely to correspond to, or be generalisable to, the real world (Campbell 1957). ‘Reproducibility’ refers to the ability of independent researchers to draw the same conclusions from the data (Kass et al. 2016).

AAC Whitehead hard white spring wheat

AAC Whitehead, an awned hard white spring wheat (Triticum aestivum L.) cultivar, combines high grain yield and good agronomic characteristics with excellent disease resistance. Based on 34 station-years of registration trial data from 2017 to 2019, AAC Whitehead had grain yield significantly higher than all of the check cultivars. AAC Whitehead had maturity similar to the checks, low lodging scores, and significantly shorter plant height than Snowstar and Whitehawk. AAC Whitehead had significantly lower test weight and higher kernel mass than than all the check cultivars. AAC Whitehead expressed resistance to the prevalent races of leaf, stripe and stem rust, and common bunt; and moderate resistance to Fusarium head blight (FHB). It also expressed tolerance to the orange wheat blossom midge. AAC Whitehead expresses quality attributes within the range of the check cultivars and is eligible for grades of Canada Western Hard White Spring wheat.

AAC Perform red spring wheat

AAC Perform, an awned hard red spring wheat (Triticum aestivum L.) cultivar, combines high grain yield and good agronomic characteristics with excellent resistance to leaf, stem, and stripe rust. Based on 43 station years of registration trial data from 2017 to 2019, the grain yield of AAC Perform was about 6% higher than AAC Foray and about 12% over AAC Penhold. AAC Perform was significantly shorter than AAC Foray and had straw strength similar to AAC Penhold. It was about two days later maturing than AAC Foray. AAC Perform had similar test weight, smaller kernel size and lower protein concentration as compared with AAC Foray. AAC Perform had milling and baking quality suitable for grades of the Canada Prairie Spring Red wheat market class.