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External data (e.g., real‐world data (RWD) and historical data) have become more readily available. This has led to rapidly increasing interest in exploring and evaluating ways of utilizing external data to facilitate traditional clinical trials (TCT), especially for rare diseases with high unmet medical needs where a TCT would be impractical and/or unethical. In this article, we focus on hybrid studies that incorporate external data into randomized clinical trials to augment the control arm and explore a complex innovative design. A sequential adaptive design conducts multiple interim assessments to improve the accuracy of estimates of agreement between external data and current data. At each interim assessment, we apply the inverse probability weighted power prior (IPW‐PP) method to adaptively borrow information from external data to account for confounding and heterogeneity. The randomization ratio is dynamically adjusted during the interim assessment based on accumulatively augmented information to reduce the sample size of the current trial. Additionally, the proposed design can be extended to allow interim analyses for early efficacy/futility stopping, that is, early assessment of trial success or failure based on accumulated data, potentially reducing ineffective treatment exposure and unnecessary time and resources. The performance of the proposed method and design is evaluated via extensive simulation studies. The sequential adaptive design and IPW‐PP approach having desirable properties are implemented. [ABSTRACT FROM AUTHOR]

ABSTRACT When multiple historical controls are available, it is necessary to consider the conflicts between current and historical controls and the relationships among historical controls. One of the assumptions concerning the relationships between the parameters of interest of current and historical controls is known as the “Potential biases.” Within the “Potential biases” assumption, the differences between the parameters of interest of the current control and of each historical control are defined as “potential bias parameters.” We define a class of models called “potential biases model” that encompass several existing methods, including the commensurate prior. The potential bias model incorporates homogeneous historical controls by shrinking the potential bias parameters to zero. In scenarios where multiple historical controls are available, a method that uses a horseshoe prior was proposed. However, various other shrinkage priors are also available. In this study, we propose methods that apply spike‐and‐slab, Dirichlet–Laplace, and spike‐and‐slab lasso priors to the potential bias model. We conduct a simulation study and analyze clinical trial examples to compare the performances of the proposed and existing methods. The horseshoe prior and the three other priors make the strongest use of historical controls in the absence of heterogeneous historical controls and reduce the influence of heterogeneous historical controls in the presence of a few historical controls. Among these four priors, the spike‐and‐slab prior performed the best for heterogeneous historical controls. [ABSTRACT FROM AUTHOR]

It is becoming increasingly popular to elicit informative priors on the basis of historical data. Popular existing priors, including the power prior, commensurate prior, and robust meta-analytic predictive prior, provide blanket discounting. Thus, if only a subset of participants in the historical data are exchangeable with the current data, these priors may not be appropriate. In order to combat this issue, propensity score approaches have been proposed. However, these approaches are only concerned with the covariate distribution, whereas exchangeability is typically assessed with parameters pertaining to the outcome. In this paper, we introduce the latent exchangeability prior (LEAP), where observations in the historical data are classified into exchangeable and non-exchangeable groups. The LEAP discounts the historical data by identifying the most relevant subjects from the historical data. We compare our proposed approach against alternative approaches in simulations and present a case study using our proposed prior to augment a control arm in a phase 3 clinical trial in plaque psoriasis with an unbalanced randomization scheme. [ABSTRACT FROM AUTHOR]

While the SARS-CoV-2 (COVID-19) pandemic has led to an impressive and unprecedented initiation of clinical research, it has also led to considerable disruption of clinical trials in other disease areas, with around 80% of non-COVID-19 trials stopped or interrupted during the pandemic. In many cases the disrupted trials will not have the planned statistical power necessary to yield interpretable results. This article describes methods to compensate for the information loss arising from trial disruptions by incorporating additional information available from auxiliary data sources. The methods described include the use of auxiliary data on baseline and early outcome data available from the trial itself and frequentist and Bayesian approaches for the incorporation of information from external data sources. The methods are illustrated by application to the analysis of artificial data based on the Primary care pediatrics Learning Activity Nutrition (PLAN) study, a clinical trial assessing a diet and exercise intervention for overweight children, that was affected by the COVID-19 pandemic. We show how all of the methods proposed lead to an increase in precision relative to use of complete case data only. [ABSTRACT FROM AUTHOR]

Abstract Background Economic evaluation of emerging health technologies is mandated by agencies such as the National Institute for Health and Care Excellence (NICE) to ensure their cost is proportional to their benefit. To avoid bias, NICE stipulate that the benefit of a treatment is assessed across the lifetime of the patient population, which can be many decades. Unfortunately, follow-up from a clinical trial will not usually cover the required period and the observed follow-up will require extrapolation. For survival data this is often done by selecting a preferred model from a set of candidate parametric models. This approach is limited in that the choice of model is restricted to those originally fitted. What if none of the models are consistent with clinical prediction or external data? Method/Results This paper introduces SurvInt, a tool that estimates the parameters of common parametric survival models which interpolate key survival time co-ordinates specified by the user, which could come from external trials, real world data or expert clinical opinion. This is achieved by solving simultaneous equations based on the survival functions of the parametric models. The application of SurvInt is shown through two examples where traditional parametric modelling did not produce models that were consistent with external data or clinical opinion. Additional features include model averaging, mixture cure models, background mortality, piecewise modelling, restricted mean survival time estimation and probabilistic sensitivity analysis. Conclusions SurvInt allows precise parametric survival models to be estimated and carried forward into economic models. It provides access to extrapolations that are consistent with multiple data sources such as observed data and clinical predictions, opening the door to precise exploration of regions of uncertainty/disagreement. SurvInt could avoid the need for post-hoc adjustments for complications such as treatment switching, which are often applied to obtain a plausible survival model but at the cost of introducing additional uncertainty. Phase III clinical trials are not designed with extrapolation in mind, and so it is sensible to consider alternative approaches to predict future survival that incorporate external information.

Abstract Background Health policy decisions are often informed by estimates of long-term survival based primarily on short-term data. A range of methods are available to include longer-term information, but there has previously been no comprehensive and accessible tool for implementing these. Results This paper introduces a novel model and software package for parametric survival modelling of individual-level, right-censored data, optionally combined with summary survival data on one or more time periods. It could be used to estimate long-term survival based on short-term data from a clinical trial, combined with longer-term disease registry or population data, or elicited judgements. All data sources are represented jointly in a Bayesian model. The hazard is modelled as an M-spline function, which can represent potential changes in the hazard trajectory at any time. Through Bayesian estimation, the model automatically adapts to fit the available data, and acknowledges uncertainty where the data are weak. Therefore long-term estimates are only confident if there are strong long-term data, and inferences do not rely on extrapolating parametric functions learned from short-term data. The effects of treatment or other explanatory variables can be estimated through proportional hazards or with a flexible non-proportional hazards model. Some commonly-used mechanisms for survival can also be assumed: cure models, additive hazards models with known background mortality, and models where the effect of a treatment wanes over time. All of these features are provided for the first time in an R package, survextrap, in which models can be fitted using standard R survival modelling syntax. This paper explains the model, and demonstrates the use of the package to fit a range of models to common forms of survival data used in health technology assessments. Conclusions This paper has provided a tool that makes comprehensive and principled methods for survival extrapolation easily usable.

Background: Economic evaluation of emerging health technologies is mandated by agencies such as the National Institute for Health and Care Excellence (NICE) to ensure their cost is proportional to their benefit. To avoid bias, NICE stipulate that the benefit of a treatment is assessed across the lifetime of the patient population, which can be many decades. Unfortunately, follow-up from a clinical trial will not usually cover the required period and the observed follow-up will require extrapolation. For survival data this is often done by selecting a preferred model from a set of candidate parametric models. This approach is limited in that the choice of model is restricted to those originally fitted. What if none of the models are consistent with clinical prediction or external data? Method/Results: This paper introduces SurvInt, a tool that estimates the parameters of common parametric survival models which interpolate key survival time co-ordinates specified by the user, which could come from external trials, real world data or expert clinical opinion. This is achieved by solving simultaneous equations based on the survival functions of the parametric models. The application of SurvInt is shown through two examples where traditional parametric modelling did not produce models that were consistent with external data or clinical opinion. Additional features include model averaging, mixture cure models, background mortality, piecewise modelling, restricted mean survival time estimation and probabilistic sensitivity analysis. Conclusions: SurvInt allows precise parametric survival models to be estimated and carried forward into economic models. It provides access to extrapolations that are consistent with multiple data sources such as observed data and clinical predictions, opening the door to precise exploration of regions of uncertainty/disagreement. SurvInt could avoid the need for post-hoc adjustments for complications such as treatment switching, which are often applied to obtain a plausible survival model but at the cost of introducing additional uncertainty. Phase III clinical trials are not designed with extrapolation in mind, and so it is sensible to consider alternative approaches to predict future survival that incorporate external information. [ABSTRACT FROM AUTHOR]

The power of machine learning is widely leveraged in the task of company stock price prediction. It is essential to incorporate historical stock prices and relevant external world information for constructing a more accurate predictive model. The sentiments of the financial news connected with the company can become such valuable knowledge. However, financial news has different topics, such as Macro, Markets, or Product news. The adoption of such categorization is usually out of scope in a market research. In this work, we aim to close this gap and explore the effect of capturing the news topic differentiation in the stock price prediction problem. Initially, we classify the financial news stream into 20 pre-defined topics with the pre-trained model. Then, we get sentiments and explore the topic of news group sentiment labeling. Moreover, we conduct the experiments with the several well-proved models for time series forecasting, including the Temporal Convolutional Network (TCN), the D-Linear, the Transformer, and the Temporal Fusion Transformer (TFT). In the results of our research, utilizing the information from separate topic groups contributes to a better performance of deep learning models compared to the approach when we consider all news sentiments without any division. [ABSTRACT FROM AUTHOR]

Background: Health policy decisions are often informed by estimates of long-term survival based primarily on short-term data. A range of methods are available to include longer-term information, but there has previously been no comprehensive and accessible tool for implementing these. Results: This paper introduces a novel model and software package for parametric survival modelling of individual-level, right-censored data, optionally combined with summary survival data on one or more time periods. It could be used to estimate long-term survival based on short-term data from a clinical trial, combined with longer-term disease registry or population data, or elicited judgements. All data sources are represented jointly in a Bayesian model. The hazard is modelled as an M-spline function, which can represent potential changes in the hazard trajectory at any time. Through Bayesian estimation, the model automatically adapts to fit the available data, and acknowledges uncertainty where the data are weak. Therefore long-term estimates are only confident if there are strong long-term data, and inferences do not rely on extrapolating parametric functions learned from short-term data. The effects of treatment or other explanatory variables can be estimated through proportional hazards or with a flexible non-proportional hazards model. Some commonly-used mechanisms for survival can also be assumed: cure models, additive hazards models with known background mortality, and models where the effect of a treatment wanes over time. All of these features are provided for the first time in an R package, survextrap, in which models can be fitted using standard R survival modelling syntax. This paper explains the model, and demonstrates the use of the package to fit a range of models to common forms of survival data used in health technology assessments. Conclusions: This paper has provided a tool that makes comprehensive and principled methods for survival extrapolation easily usable. [ABSTRACT FROM AUTHOR]

Bayesian methods have been proposed as a natural fit for pediatric extrapolation, as they allow the incorporation of relevant external data to reduce the required sample size and hence trial burden for the pediatric patient population. In this paper we will discuss our experience and perspectives with these methods in pediatric trials. We will present some of the background and thinking underlying pediatric extrapolation and discuss the use of Bayesian methods within this context. We will present two recent case examples illustrating the value of a Bayesian approach in this setting and present perspectives on some of the issues that we have encountered in these and other cases. [ABSTRACT FROM AUTHOR]

The power of randomized controlled clinical trials to demonstrate the efficacy of a drug compared with a control group depends not just on how efficacious the drug is, but also on the variation in patients' outcomes. Adjusting for prognostic covariates during trial analysis can reduce this variation. For this reason, the primary statistical analysis of a clinical trial is often based on regression models that besides terms for treatment and some further terms (e.g., stratification factors used in the randomization scheme of the trial) also includes a baseline (pre‐treatment) assessment of the primary outcome. We suggest to include a "super‐covariate"—that is, a patient‐specific prediction of the control group outcome—as a further covariate (but not as an offset). We train a prognostic model or ensembles of such models on the individual patient (or aggregate) data of other studies in similar patients, but not the new trial under analysis. This has the potential to use historical data to increase the power of clinical trials and avoids the concern of type I error inflation with Bayesian approaches, but in contrast to them has a greater benefit for larger sample sizes. It is important for prognostic models behind "super‐covariates" to generalize well across different patient populations in order to similarly reduce unexplained variability whether the trial(s) to develop the model are identical to the new trial or not. In an example in neovascular age‐related macular degeneration we saw efficiency gains from the use of a "super‐covariate". [ABSTRACT FROM AUTHOR]

Data analysis in modern scientific research and practice has shifted from analysing a single dataset to coupling several datasets. We propose and study a kernel regression method that can handle the challenge of heterogeneous populations. It greatly extends the constrained kernel regression [Dai, C.-S., & Shao, J. (2023). Kernel regression utilizing external information as constraints. Statistica Sinica, 33, in press] that requires a homogeneous population of different datasets. The asymptotic normality of proposed estimators is established under some conditions and simulation results are presented to confirm our theory and to quantify the improvements from datasets with heterogeneous populations.

The breakthrough propensity score methodology was formulated by Rosenbaum and Rubin in the 1980s for the mitigation of confounding bias in non‐randomized comparative studies to facilitate causal inference for treatment effects. The methodology had been used mainly in epidemiological and social science studies that may often be exploratory, until it was adopted by FDA/CDRH in 2002 and applied in the evaluation of medical device pre‐market confirmatory studies, including those with a control group extracted from a well‐designed and executed registry database or historical clinical studies. Around 2013, following the Rubin outcome‐free study design principle, the two‐stage propensity score design framework was developed for medical device studies to safeguard study integrity and objectivity, thereby strengthening the interpretability of study results. Since 2018, the scope of the propensity score methodology has been broadened so that it can be used for the purpose of leveraging external data to augment a single‐arm or randomized traditional clinical study. All these statistical approaches, collectively referred to as propensity score‐based methods in this article, have been considered in the design of medical device regulatory studies and stimulated related research, as evidenced by the latest trends in journal publications. We will provide a tutorial on the propensity score‐based methods from the basic idea to their implementation in regulatory settings for causal inference and external data leveraging, along with step‐by‐step descriptions of the procedures of the two‐stage outcome‐free design through examples, which can be used as templates for real study proposals. [ABSTRACT FROM AUTHOR]

Abstract Background To improve the efficiency of clinical trials, leveraging external data on control and/or treatment effects, which is almost always available, appears to be a promising approach. Methods We used data from the experimental arm of the Covidicus trial evaluating high-dose dexamethasone in severely ill and mechanically ventilated COVID-19 patients, using published data from the Recovery trial as external data, to estimate the 28-day mortality rate. Primary approaches to deal with external data were applied. Results Estimates ranged from 0.241 ignoring the external data up to 0.294 using hierarchical Bayesian models. Some evidence of differences in mortality rates between the Covidicus and Recovery trials were observed, with an matched adjusted odds ratio of death in the Covidicus arm of 0.41 compared to the Recovery arm. Conclusions These indirect comparisons appear sensitive to the method used. None of those approaches appear robust enough to overcome randomized clinical trial data. Trial registration Covidicus Trial: NCT04344730, First Posted: 14/04/2020; Recovery trial: NCT04381936

Objectives: Immuno-oncology (IO) therapies are often associated with delayed responses that are deep and durable, manifesting as long-term survival benefits in patients with metastatic cancer. Complex hazard functions arising from IO treatments may limit the accuracy of extrapolations from standard parametric models (SPMs). We evaluated the ability of flexible parametric models (FPMs) to improve survival extrapolations using data from 2 trials involving patients with non–small-cell lung cancer (NSCLC). Methods: Our analyses used consecutive database locks (DBLs) at 2-, 3-, and 5-y minimum follow-up from trials evaluating nivolumab versus docetaxel in patients with pretreated metastatic squamous (CheckMate-017) and nonsquamous (CheckMate-057) NSCLC. For each DBL, SPMs, as well as 3 FPMs—landmark response models (LRMs), mixture cure models (MCMs), and Bayesian multiparameter evidence synthesis (B-MPES)—were estimated on nivolumab overall survival (OS). The performance of each parametric model was assessed by comparing milestone restricted mean survival times (RMSTs) and survival probabilities with results obtained from externally validated SPMs. Results: For the 2- and 3-y DBLs of both trials, all models tended to underestimate 5-y OS. Predictions from nonvalidated SPMs fitted to the 2-y DBLs were highly unreliable, whereas extrapolations from FPMs were much more consistent between models fitted to successive DBLs. For CheckMate-017, in which an apparent survival plateau emerges in the 3-y DBL, MCMs fitted to this DBL estimated 5-y OS most accurately (11.6% v. 12.3% observed), and long-term predictions were similar to those from the 5-y validated SPM (20-y RMST: 30.2 v. 30.5 mo). For CheckMate-057, where there is no clear evidence of a survival plateau in the early DBLs, only B-MPES was able to accurately predict 5-y OS (14.1% v. 14.0% observed [3-y DBL]). Conclusions: We demonstrate that the use of FPMs for modeling OS in NSCLC patients from early follow-up data can yield accurate estimates for RMST observed with longer follow-up and provide similar long-term extrapolations to externally validated SPMs based on later data cuts. B-MPES generated reasonable predictions even when fitted to the 2-y DBLs of the studies, whereas MCMs were more reliant on longer-term data to estimate a plateau and therefore performed better from 3 y. Generally, LRM extrapolations were less reliable than those from alternative FPMs and validated SPMs but remained superior to nonvalidated SPMs. Our work demonstrates the potential benefits of using advanced parametric models that incorporate external data sources, such as B-MPES and MCMs, to allow for accurate evaluation of treatment clinical and cost-effectiveness from trial data with limited follow-up. Highlights: Flexible advanced parametric modeling methods can provide improved survival extrapolations for immuno-oncology cost-effectiveness in health technology assessments from early clinical trial data that better anticipate extended follow-up. Advantages include leveraging additional observable trial data, the systematic integration of external data, and more detailed modeling of underlying processes. Bayesian multiparameter evidence synthesis performed particularly well, with well-matched external data. Mixture cure models also performed well but may require relatively longer follow-up to identify an emergent plateau, depending on the specific setting. Landmark response models offered marginal benefits in this scenario and may require greater numbers in each response group and/or increased follow-up to support improved extrapolation within each subgroup. [ABSTRACT FROM AUTHOR]

The discussions of our paper provide insights into the practical considerations of the latent exchangeability prior while also highlighting further extensions. In this rejoinder, we briefly summarize the discussions and provide comments. [ABSTRACT FROM AUTHOR]

Background: To improve the efficiency of clinical trials, leveraging external data on control and/or treatment effects, which is almost always available, appears to be a promising approach. Methods: We used data from the experimental arm of the Covidicus trial evaluating high-dose dexamethasone in severely ill and mechanically ventilated COVID-19 patients, using published data from the Recovery trial as external data, to estimate the 28-day mortality rate. Primary approaches to deal with external data were applied. Results: Estimates ranged from 0.241 ignoring the external data up to 0.294 using hierarchical Bayesian models. Some evidence of differences in mortality rates between the Covidicus and Recovery trials were observed, with an matched adjusted odds ratio of death in the Covidicus arm of 0.41 compared to the Recovery arm. Conclusions: These indirect comparisons appear sensitive to the method used. None of those approaches appear robust enough to overcome randomized clinical trial data. Trial registration: Covidicus Trial: NCT04344730, First Posted: 14/04/2020; Recovery trial: NCT04381936 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pediatric cancer consists of a diverse group of rare diseases. The relatively small population of children with multiple, disparate tumor types across various age groups presents a significant challenge for drug development programs as compared to oncology drug development programs for adults. A recent review paper searched the written requests that were issued by the US FDA between 2001 and 2019. Many of the completed pediatric trials over the past 19 years have led to conclusions that the cancer drugs developed for adult cancer indications have not demonstrated sufficient effectiveness within the context of limited phase 1 and/or phase 2 studies in heavily pretreated patients (Akalu et al. in Pediatr Blood Cancer. https://doi.org/10.1002/pbc.28828, 2020). Faster learning and the implementation of futility criteria in the trial design should be considered in pediatric trials when the potential beneficial effects of investigational drugs may be unclear. In this paper, the authors compare the commonly used Simon's 2-stage design in pediatric cancer trials to Bayesian sequential monitoring. The results show that the chance to stop for futility is at least doubled when a Bayesian design is used when compared to Simon's 2-stage. The lower the true response rates are, the greater the number of patients would be saved from exposure to an ineffective treatment. To overcome the limitation of a small population and limited extrapolation opportunities, the innovative approach using Bayesian strategy to allow leveraging adult or external data in pediatric cancer trials should be considered. [ABSTRACT FROM AUTHOR]

External data, referred to as data external to the traditional clinical study being planned, include but are not limited to real-world data (RWD) and data collected from clinical studies being conducted in the past or in other countries. The external data are sometimes leveraged to augment a single-arm, prospectively designed study when appropriate. In such an application, recently developed propensity score-integrated approaches including PSPP and PSCL can be used for study design and data analysis when the clinical outcomes are binary or continuous. In this paper, the propensity score-integrated Kaplan–Meier (PSKM) method is proposed for a similar situation but the outcome of interest is time-to-event. The propensity score methodology is used to select external subjects that are similar to those in the current study in terms of baseline covariates and to stratify the selected subjects from both data sources into more homogeneous strata. The stratum-specific PSKM estimators are obtained based on all subjects in the stratum with the external data being down-weighted, and then these estimators are combined to obtain an overall PSKM estimator. A simulation study is conducted to assess the performance of the PSKM method, and an illustrative example is presented to demonstrate how to implement the proposed method. [ABSTRACT FROM AUTHOR]

Financial reporting and assurance in their current form are losing relevance to investors in firm valuations. New sources of data, especially exogenous or external data that are generated outside the organizations, have opened doors to new ways of business measurement and information validation. Examples of exogenous data include social media, online searches, social networks, and news media. This paper discusses the state-of-the-art applications of exogenous data in the measurement and assurance of business reporting, ESG, and cybersecurity and provides potential avenues for future research. Furthermore, this paper speculates on the nature of the new paradigm of business measurement and assurance with exogenous data and the difficulties that are emerging. [ABSTRACT FROM AUTHOR]

The incorporation of suitable external data from the World Wide Web offers an effective solution for enriching the data in the data warehouse (DW). However, the main challenge is the quality‐aware selection of web data sources to maintain the quality of the DW. In the previous works, the quality evaluation of web sources is through expert evaluation only, which makes it a very lengthy process. Also, since the quality model consists of mixed quality factors from diverse domains of Web, DW and underlying business, finding an expert possessing an expertise of all these domains is a huge bottleneck in the evaluation process. In order to overcome these existing issues, this study proposes a novel multi‐level approach web source evaluation with multi‐criteria decision‐making and web quality testing tools (WSEMQT) and underlying quality model web quality model for evaluating web sources for the DW. The authors introduce automated web source quality evaluation in the first level of web source based evaluation and multiple dimensions of quality evaluation at the second level of expert‐based evaluation. At both the levels, multi‐criteria decision‐making methods are applied to the evaluation scores obtained to ascertain the ranked list of Web sources. The authors present a real‐world academic web data case study which shows that the proposed approach can be executed successfully for real‐world problems. [ABSTRACT FROM AUTHOR]

There is an increasing demand for utilization of external data, such as historical study data and patient registry data, to augment the control group in a randomized controlled trial. While such a study design could reduce the time and cost, how to maintain the study validity and integrity is one major statistical challenge that needs to be carefully addressed. We discuss a study design quality process to enhance the study validity and integrity when using this approach. The discussed quality process is tailored to the confirmatory study using a 2-stage design with an emphasis on the interaction process among stakeholders. In an example, the quality process covers a 2-step assessment of the similarity in patient characteristics between the current study and the external data source, and between the treatment and augmented control groups. [ABSTRACT FROM AUTHOR]

BI solutions are constantly being developed to support decision-making at various organisational levels. These solutions facilitate the compilation, aggregation and summarisation of large volumes of data. Consequently, the business value created by these systems is increasing as they sustain more and more advanced analytics, ranging from descriptive analytics, to predictive analytics, to prescriptive analytics. However, most organisations work primarily with internal data. Despite many references in the literature to the value hidden in external data, details on how such data can be used are scarce. In this paper, we present the results of an extensive action case study at a public waste management company. The results illustrate how external data from several external data sources, integrated into an up-and-running BI solution, are used jointly to allow for descriptive and predictive analytics, as well as prescriptive analytics. In addition, details of these analytical values are given and related to organisational benefits. [ABSTRACT FROM AUTHOR]

Objectives. Uncertainty in survival prediction beyond trial follow-up is highly influential in cost-effectiveness analyses of oncology products. This research provides an empirical evaluation of the accuracy of alternative methods and recommendations for their implementation. Methods. Mature (15-year) survival data were reconstructed from a published database study for "no treatment," radiotherapy, surgery plus radiotherapy, and surgery in early stage non–small cell lung cancer in an elderly patient population. Censored data sets were created from these data to simulate immature trial data (for 1- to 10-year follow-up). A second data set with mature (9-year) survival data for no treatment was used to extrapolate the predictions from models fitted to the first data set. Six methodological approaches were used to fit models to the simulated data and extrapolate beyond trial follow-up. Model performance was evaluated by comparing the relative difference in mean survival estimates and the absolute error in the difference in mean survival v. the control with those from the original mature survival data set. Results. Model performance depended on the treatment comparison scenario. All models performed reasonably well when there was a small short-term treatment effect, with the Bayesian model coping better with shorter follow-up times. However, in other scenarios, the most flexible Bayesian model that could be estimated in practice appeared to fit the data less well than the models that used the external data separately. Where there was a large treatment effect (hazard ratio = 0.4), models that used external data separately performed best. Conclusions. Models that directly use mature external data can improve the accuracy of survival predictions. Recommendations on modeling strategies are made for different treatment benefit scenarios. [ABSTRACT FROM AUTHOR]