Evidence-Based Prescribing: Combining Network Meta-Analysis With Multicriteria Decision Analysis to Choose Among Multiple Drugs

What is the drug of choice for condition x? is among the most commonly asked questions in primary care.1 Reflecting the complexity of prescribing decisions, answering this question requires a difficult trade-off between the benefits and harms of multiple drugs for a given condition. The principles of evidence-based medicine suggest that prescribing decisions should be guided by an objective benchmark, namely scientific evidence.2 Such evidence is particularly important when choosing a first-line treatment among multiple alternatives. Unfortunately, existing clinical evidence on benefits and harms is rarely adequate to inform prescribing decisions. A randomized controlled trial comparing all relevant drugs would provide such information. However, clinical trials are often designed for regulatory purposes and, therefore, include selective patient populations and do not include all available comparator drugs.3,4 To obtain insight into the comparative benefits and harms of multiple drugs, prescribers turn to summaries of evidence to discern the most promising drugs from their less effective comparators. Recent methods used to synthesize existing evidence provide much-needed information on the comparative benefits and harms of multiple drugs. Network meta-analysis is one such method that allows for the combination of direct and indirect evidences from randomized trials, facilitating the comparison of all relevant drugs even when they are not directly compared with each other in clinical trials.5 The recent surge in the number of network meta-analyses in the general medical literature is a testament to the increasing need for comparative evidence in prescribing decisions.6 Even when comparative evidence from network meta-analyses exists, however, making sense of it remains a challenge. In particular, prescribers and patients often struggle to weigh the relative benefits and harms of multiple alternatives. In this proof-of-concept study, we discuss the important yet challenging role of comparative clinical evidence in guiding prescribing decisions in …

[1]  Ben Goldacre,et al.  What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice , 2014, European journal of preventive cardiology.

[2]  J. Figueira,et al.  A survey on stochastic multicriteria acceptability analysis methods , 2008 .

[3]  E. Berndt,et al.  Prescription drug spending trends in the United States: looking beyond the turning point. , 2008, Health affairs.

[4]  Alejandra Duenas,et al.  Multiple criteria decision analysis for health technology assessment. , 2012, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[5]  G. Guyatt,et al.  Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. , 2011, QJM : monthly journal of the Association of Physicians.

[6]  Tommi Tervonen,et al.  A stochastic multicriteria model for evidence‐based decision making in drug benefit‐risk analysis , 2011, Statistics in medicine.

[7]  D. Sackett,et al.  Evidence based medicine: what it is and what it isn't , 1996, BMJ.

[8]  H. Naci,et al.  Dose-comparative effects of different statins on serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials , 2013, European journal of preventive cardiology.

[9]  R. Collins,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010, The Lancet.

[10]  R. L. Keeney,et al.  Decisions with Multiple Objectives: Preferences and Value Trade-Offs , 1977, IEEE Transactions on Systems, Man, and Cybernetics.

[11]  H. Naci,et al.  Comparative effects of statins on major cerebrovascular events: a multiple-treatments meta-analysis of placebo-controlled and active-comparator trials. , 2013, QJM : monthly journal of the Association of Physicians.

[12]  R. Collins,et al.  The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials , 2012, The Lancet.

[13]  Nicky J Welton,et al.  A Generalised Linear Modelling Framework for Pairwise and Network Meta-Analysis of Randomised Controlled Trials , 2014 .

[14]  Kristian Thorlund,et al.  How to use an article reporting a multiple treatment comparison meta-analysis. , 2012, JAMA.

[15]  Huseyin Naci,et al.  Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers , 2013, BMC Medicine.

[16]  M. Gnant,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010 .

[17]  Jennifer G. Robinson,et al.  2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. , 2014, Circulation.

[18]  Drug and Therapeutics Bulletin An introduction to patient decision aids , 2013, BMJ.

[19]  Ralph L. Keeney,et al.  Decisions with multiple objectives: preferences and value tradeoffs , 1976 .

[20]  R. Collins,et al.  Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins , 2005, The Lancet.

[21]  A. Astrup,et al.  Modest weight loss in moderately overweight postmenopausal women improves heart rate variability , 2013, European journal of preventive cardiology.

[22]  R. Collins,et al.  The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. , 2012, Lancet.

[23]  G. Lu,et al.  Combination of direct and indirect evidence in mixed treatment comparisons , 2004, Statistics in medicine.

[24]  Theodor J. Stewart,et al.  Multiple criteria decision analysis - an integrated approach , 2001 .

[25]  Matthew A Silva,et al.  Statin-related adverse events: a meta-analysis. , 2006, Clinical therapeutics.

[26]  Dawn Stacey,et al.  Decision aids for people facing health treatment or screening decisions. , 2009, The Cochrane database of systematic reviews.

[27]  Kristian Thorlund,et al.  Demystifying trial networks and network meta-analysis , 2013, BMJ.

[28]  H. Naci,et al.  Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials , 2013, European journal of preventive cardiology.

[29]  Gregory Makoul,et al.  Patient preferences for shared decisions: a systematic review. , 2012, Patient education and counseling.

[30]  Alex J. Sutton,et al.  Evidence Synthesis for Decision Making 2 , 2013, Medical decision making : an international journal of the Society for Medical Decision Making.

[31]  B. Duncan,et al.  Impact of statin dose on major cardiovascular events: a mixed treatment comparison meta-analysis involving more than 175,000 patients. , 2013, International journal of cardiology.

[32]  J. Ioannidis,et al.  How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs? , 2015, Annual review of pharmacology and toxicology.

[33]  P. Gorman,et al.  A taxonomy of generic clinical questions: classification study , 2000, BMJ : British Medical Journal.

[34]  Huseyin Naci,et al.  Comparative Tolerability and Harms of Individual Statins: A Study-Level Network Meta-Analysis of 246 955 Participants From 135 Randomized, Controlled Trials , 2013, Circulation. Cardiovascular quality and outcomes.

[35]  J. Ioannidis Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials. , 1998, JAMA.

[36]  M. Matthews,et al.  Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy. , 2007, Clinical therapeutics.

[37]  J Shepherd,et al.  The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials , 2009, BMJ : British Medical Journal.

[38]  Cholesterol Treatment Trialists' Collaborato The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials , 2012 .

[39]  Elias Mossialos,et al.  Regulating Pharmaceuticals In Europe: Striving For Efficiency, Equity And Quality , 2004 .

[40]  R. Blumenthal,et al.  Nonfatal Outcomes in the Primary Prevention of Atherosclerotic Cardiovascular Disease: Is All-Cause Mortality Really All That Matters? , 2014, Circulation. Cardiovascular quality and outcomes.

[41]  Edward J. Mills,et al.  Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. , 2008, Journal of the American College of Cardiology.

[42]  J. Cylus,et al.  Evidence of Comparative Efficacy Should Have a Formal Role in European Drug Approvals Article (published Version) (refereed) , 2022 .

[43]  Tommi Tervonen,et al.  Multicriteria benefit-risk assessment using network meta-analysis. , 2012, Journal of clinical epidemiology.

[44]  M. Briel,et al.  Adverse events associated with individual statin treatments for cardiovascular disease: an indirect comparison meta-analysis. , 2012, QJM : monthly journal of the Association of Physicians.

[45]  Tommi Tervonen,et al.  Hit-And-Run enables efficient weight generation for simulation-based multiple criteria decision analysis , 2013, Eur. J. Oper. Res..

[46]  E. Rahme,et al.  Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention. , 2006, American heart journal.

[47]  Deborah M Caldwell,et al.  Simultaneous comparison of multiple treatments: combining direct and indirect evidence , 2005, BMJ : British Medical Journal.

[48]  R. Thomson,et al.  Decision aids for people facing health treatment or screening decisions. , 2003, The Cochrane database of systematic reviews.

[49]  J. Cylus,et al.  Raising the bar for market authorisation of new drugs , 2012, BMJ : British Medical Journal.

[50]  Deborah M Caldwell,et al.  Selecting the best scale for measuring treatment effect in a network meta‐analysis: a case study in childhood nocturnal enuresis , 2012, Research synthesis methods.

[51]  An introduction to patient decision aids , 2012, Drug and Therapeutics Bulletin.