Algorithmic parameterization of mixed treatment comparisons

Mixed Treatment Comparisons (MTCs) enable the simultaneous meta-analysis (data pooling) of networks of clinical trials comparing ≥2 alternative treatments. Inconsistency models are critical in MTC to assess the overall consistency between evidence sources. Only in the absence of considerable inconsistency can the results of an MTC (consistency) model be trusted. However, inconsistency model specification is non-trivial when multi-arm trials are present in the evidence structure. In this paper, we define the parameterization problem for inconsistency models in mathematical terms and provide an algorithm for the generation of inconsistency models. We evaluate running-time of the algorithm by generating models for 15 published evidence structures

Automated generation of node-splitting models for assessment of inconsistency in network meta-analysis

Network meta-analysis enables the simultaneous synthesis of a network of clinical trials comparing any number of treatments. Potential inconsistencies between estimates of relative treatment effects are an important concern, and several methods to detect inconsistency have been proposed. This paper is concerned with the node-splitting approach, which is particularly attractive because of its straightforward interpretation, contrasting estimates from both direct and indirect evidence. However, node-splitting analyses are labour-intensive because each comparison of interest requires a separate model. It would be advantageous if node-splitting models could be estimated automatically for all comparisons of interest. We present an unambiguous decision rule to choose which comparisons to split, and prove that it selects only comparisons in potentially inconsistent loops in the network, and that all potentially inconsistent loops in the network are investigated. Moreover, the decision rule circumvents problems with the parameterisation of multi-arm trials, ensuring that model generation is trivial in all cases. Thus, our methods eliminate most of the manual work involved in using the node-splitting approach, enabling the analyst to focus on interpreting the results. (C) 2015 The Authors Research Synthesis Methods Published by John Wiley & Sons Ltd

Applying multiple criteria decision analysis to comparative benefit-risk assessment: choosing among statins in primary prevention

Decision makers in different health care settings need to weigh the benefits and harms of alternative treatment strategies. Such health care decisions include marketing authorization by regulatory agencies, practice guideline formulation by clinical groups, and treatment selection by prescribers and patients in clinical practice. Multiple criteria decision analysis (MCDA) is a family of formal methods that help make explicit the tradeoffs that decision makers accept between the benefit and risk outcomes of different treatment options. Despite the recent interest in MCDA, certain methodological aspects are poorly understood. This paper presents 7 guidelines for applying MCDA in benefitrisk assessment and illustrates their use in the selection of a statin drug for the primary prevention of cardiovascular disease. We provide guidance on the key methodological issues of how to define the decision problem, how to select a set of nonoverlapping evaluation criteria, how to synthesize and summarize the evidence, how to translate relative measures to absolute ones that permit comparisons between the criteria, how to define suitable scale ranges, how to elicit partial preference information from the decision makers, and how to incorporate uncertainty in the analysis. Our example on statins indicates that fluvastatin is likely to be the most preferred drug by our decision maker and that this result is insensitive to the amount of preference information incorporated in the analysis

A multi-criteria decision analysis perspective on the health economic evaluation of medical interventions

Abstract A standard practice in health economic evaluation is to monetize health effects by assuming a certain societal willingness-to-pay per unit of health gain. Although the resulting net monetary benefit (NMB) is easy to compute, the use of a single willingness-to-pay threshold assumes expressibility of the health effects on a single nonmonetary scale. To relax this assumption, this article proves that the NMB framework is a special case of the more general stochastic multi-criteria acceptability analysis (SMAA) method. Specifically, as SMAA does not restrict the number of criteria to two and also does not require the marginal rates of substitution to be constant, there are problem instances for which the use of this more general method may result in a better understanding of the tradeoffs underlying the reimbursement decision-making problem. This is illustrated by applying both methods in a case study related to infertility treatment

Automating network meta-analysis

Abstract Mixed Treatment Comparison (MTC) (also called network meta-analysis) is an extension of traditional meta-analysis to allow the simultaneous pooling of data from clinical trials comparing more than two treatment options. Typically, MTCs are performed using general purpose Markov Chain Monte Carlo (MCMC) software such as WinBUGS, requiring a model and data to be specified using a specific syntax. It would be preferable if, for the most common cases, both could be derived from a well-structured data file that can be easily checked for errors. Automation is particularly valuable for simulation studies in which the large number of MTCs that have to be estimated may preclude manual model specification and analysis. Moreover, automated model generation raises issues that provide additional insight into the nature of MTC. We present a method for the automated generation of Bayesian homogeneous variance random effects consistency models, including the choice of basic parameters and trial baselines, priors, and starting values for the Markov chain(s). We validate our method against the results of five published MTCs. The method is implemented in freely available open source software. This means that performing an MTC no longer requires manually writing a statistical model. This reduces time and effort, and facilitates error checking of the data set

Individual Trade-Offs Between Possible Benefits and Risks of Cancer Treatments:Results from a Stated Preference Study with Patients with Multiple Myeloma

BackgroundThe objectives of this study were to elicit the preferences of patients with multiple myeloma regarding the possible benefits and risks of cancer treatments and to illustrate how such data may be used to estimate patients' acceptance of new treatments. Patients and MethodsPatients with multiple myeloma from the cancer charity Myeloma UK were invited to participate in an online survey based on multicriteria decision analysis and swing weighting to elicit individual stated preferences for the following attributes: (a) 1-year progression-free survival (PFS, ranging from 50% to 90%), (b) mild or moderate toxicity for 2 months or longer (ranging from 85% to 45%), and (c) severe or life-threatening toxicity (ranging from 80% to 20%). ResultsA total of 560 participants completed the survey. The average weight given to PFS was 0.54, followed by 0.32 for severe or life-threatening toxicity and 0.14 for mild or moderate chronic toxicity. Participants who ranked severe or life-threatening toxicity above mild or moderate chronic toxicity (56%) were more frequently younger, working, and looking after dependent family members and had more frequently experienced severe or life-threatening side effects. The amount of weight given to PFS did not depend on any of the collected covariates. The feasibility of using the collected preference data to estimate the patients' acceptance of specific multiple myeloma treatments was demonstrated in a subsequent decision analysis example. ConclusionStated preference studies provide a systematic approach to gain knowledge about the distribution of preferences in the population and about what this implies for patients' acceptance of specific treatments. Implications for PracticeThis study demonstrated how quantitative preference statements from a large group of participants can be collected through an online survey and how such information may be used to explore the acceptability of specific treatments based on the attributes studied. Results from such studies have the potential to become an important new tool for gathering patient views and studying heterogeneity in preferences in a systematic way, along with other methods, such as focus groups and expert opinions. The objectives of this study were to ascertain the treatment preferences of patients with multiple myeloma, considering benefits and risks of particular cancer treatments, and to illustrate how such data may be used to estimate patients' acceptance of new treatments

Deficiencies in the transfer and availability of clinical trials evidence: A review of existing systems and standards

Background: Decisions concerning drug safety and efficacy are generally based on pivotal evidence provided by clinical trials. Unfortunately, finding the relevant clinical trials is difficult and their results are only available in text-based reports. Systematic reviews aim to provide a comprehensive overview of the evidence in a specific area, but may not provide the data required for decision making. Methods: We review and analyze the existing information systems and standards for aggregate level clinical trials information from the perspective of systematic review and evidence-based decision making. Results: The technology currently used has major shortcomings, which cause deficiencies in the transfer, traceability and availability of clinical trials information. Specifically, data available to decision makers is insufficiently structured, and consequently the decisions cannot be properly traced back to the underlying evidence. Regulatory submission, trial publication, trial registration, and systematic review produce unstructured datasets that are insufficient for supporting evidence-based decision making. Conclusions: The current situation is a hindrance to policy decision makers as it prevents fully transparent decision making and the development of more advanced decision support systems. Addressing the identified deficiencies would enable more efficient, informed, and transparent evidence-based medical decision making

Processing and similarity scoring WHO ICTRP data

Source code for "Previously Unidentified Duplicate Registrations of Clinical Trials: an Exploratory Analysis of Registry Data Worldwide" (under review). This code was used to process the WHO International Clinical Trials Registry Platform (ICTRP) dataset retrieved in April 2015 (see related). The code imports the XML data into a SQL database and performs a number of standardizations. There is also code to group records by referenced primary registry IDs and to perform text-based similarity scoring on registration fields. The README file included with the code provides detailed instructions on dependencies and running the code