Freemantle, N

Pagano, D

UCL Discovery

Dear Sir / Madam Conclusions methodologically unsound and risks unnecessary and avoidable deaths in patients The recent collaborative individual patient meta analysis on PCI versus CABG by Head et al (2018)[1] is a very welcome addition to the literature, establishing convincingly the superiority of CABG over PCI on the important outcome of all cause mortality (HR 1·20, 95% CI 1·06–1·37; p=0·004).  However the conclusions offered by the authors are methodologically incorrect and their publication in a major journal surprising.[2] The challenges of subgroup analyses are well known including to readers of this journal [3,4,5] and must be established on the basis of both prespecified biological plausibility and statistical rigour.  Accounting for multiplicity, none of the tests for interaction undertaken by the authors are statistically significant.  Thus the correct interpretation is that the main effect (benefit for CABG over PCI) should be applied to all subgroups including patients with left main disease.  The suggestion in the paper by Head et al (2018) that the lack of benefit found in many subgroups supports a conclusion differing from this is methodologically unsound and risk unnecessary and avoidable deaths in patients.  These points should be corrected. Nick Freemantle PhD, Institute of Clinical Trials and Methodology, University College London, Gower Street, London UK Domenico Pagano, Quality and Outcomes Research Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.  1. Head SJ, Milojevic M, Daemen J, Ahn JM, Boersma E, Christiansen EH et al.  Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data.  Lancet 2018;391:939-48 2. Freemantle N, Ruel M, Gaudino MFL, Pagano D.  On the pooling and subgrouping of data from percutaneous coronary intervention versus coronary artery bypass grafting trials: a call to circumspection.  European Journal of Cardiothoracic Surgery, 10.1093/ejcts/ezy140. 3. Yusuf S, Wittes J, Probstfield J, Tyroler HA.  Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials.  JAMA. 1991; 266: 93-8 4. Freemantle N. Interpreting the results of secondary endpoints and subgroup analyses in clinical trials: should we lock the crazy aunt in the attic?  British Medical Journal, 2001; 322: 989-91. 5. Assmann SF, Pocock SJ, Enos LE, Kasten LE.  Subgroup analysis and other (mis)uses of baseline data in clinical trials.  Lancet 2000; 355: 1064–69  

Interpretation of results of pooled analysis of individual patient data

http://discovery.ucl.ac.uk/10056990/1/Freemantle_Draft%201%20Lancet%20correspondence..pdf

Interpretation of results of pooled analysis of individual patient data

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