(1 of 4) Network Meta-Analysis Series: Relative Safety and Efficacy of New Marketing Drugs
Background
Network meta-analysis provides a global estimate of effectiveness of intervention regimes, by establishing a network between regimes combining both direct and indirect evidence from trial studies.
Meta-analyses of randomized controlled trials are considered the top of the hierarchy of clinical evidence. However, oftentimes, head-to-head comparisons are not available or are insufficient to answer a specific clinical question. NMA overcomes this limitation by providing a global estimate of efficacy or safety of multiple intervention regimes that have limited or no direct comparisons. Furthermore, NMA allows for ranking of the intervention regimes to allow for identification of the best option amongst all available options, provided that the statistical inference is valid. This appeals to clinicians and other decision makers as NMA can be used to answer the important question of “Which treatment is the best or worst?”
In pharmaceutical industry, in the absence of head-to-head trials directly comparing new marketing drug and other currently marketed treatments, the network meta-analysis (NMA) aims to generate evidence in the relative safety and effectiveness of new drugs compared with other commercially available therapies in the patients with specific diseases that are specified in new drug specification.
Method
Data sources and search strategy
Data on efficacy trials of new drug as an add-on to first line treatments (placebo) will be available and provided by the company who developed this new drug. These may comprise of several randomized, double-blind, placebo-controlled phase 2 and / or 3 clinical trials in patients who are met the inclusion and exclusion criteria in new drug study design.
We will perform a systematic review of the literatures up to the end of expected date of completion. The following databases will be searched form their dates of inception: the Cochrane library collections, Embase, MEDLINE, and MEDLINE In-Process. Search strategy will be constructed in the PICO format where target patient populations (P) will be combined with interventions (I), comparators (C), and outcomes (O) of interest. Relevant search terms will be used for each domain of the strategy. Records identified through other databases where retrieval of the complete data is deemed difficult will not be included. We will also search for other systematic reviews on add-on therapies to certain first line treatments (Placebo) to identify possible studies which can be included in our analysis.
Study selection:
The eligible studies will be identified from the search based on their study designs (e.g. double-blind, randomized, placebo- or alternative treatment- controlled trials), study duration (e.g. minimum of 6 weeks), safety and/or efficacy outcomes of interest (i.e. efficacy endpoints and safety endpoints of adverse event), and target populations. Studies sufficiently dissimilar to trials conducted for new drug will not be included.
Outcome measures:
The primary efficacy outcome measurements will be the primary efficacy endpoint of clinical trials from new drug company. Secondary efficacy outcomes will include major secondary efficacy endpoints in the clinical trials. Safety endpoints will include adverse events (AEs); as well as patient withdrawals due to any reason. Data on mortality and/or measurements of health (disease specific or generic preference based) will be included if we are able to obtain sufficient evidence
In our next blog…
we’ll cover the statistical synthesis of study data.