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Research

Estimating treatment effects for individual patients based on the results of randomised clinical trials

BMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d5888 (Published 03 October 2011) Cite this as: BMJ 2011;343:d5888
  1. Johannes A N Dorresteijn, epidemiologist and medical doctor1,
  2. Frank L J Visseren, professor of vascular medicine, epidemiologist, and internist1,
  3. Paul M Ridker, Eugene Braunwald professor of medicine, epidemiologist, and cardiologist2,
  4. Annemarie M J Wassink, internist and postdoctoral researcher1,
  5. Nina P Paynter, assistant professor of epidemiology 2,
  6. Ewout W Steyerberg, professor of medical decision making, and methodologist3,
  7. Yolanda van der Graaf, professor of epidemiology and imaging4,
  8. Nancy R Cook, associate professor of biostatistics and epidemiology2
  1. 1Department of Vascular Medicine, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, Netherlands
  2. 2Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  3. 3Department of Public Health, Erasmus Medical Center, Rotterdam, Netherlands
  4. 4Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands
  1. Correspondence to: F L J Visseren F.L.J.Visseren{at}umcutrecht.nl
  • Accepted 12 August 2011

Abstract

Objectives To predict treatment effects for individual patients based on data from randomised trials, taking rosuvastatin treatment in the primary prevention of cardiovascular disease as an example, and to evaluate the net benefit of making treatment decisions for individual patients based on a predicted absolute treatment effect.

Setting As an example, data were used from the Justification for the Use of Statins in Prevention (JUPITER) trial, a randomised controlled trial evaluating the effect of rosuvastatin 20 mg daily versus placebo on the occurrence of cardiovascular events (myocardial infarction, stroke, arterial revascularisation, admission to hospital for unstable angina, or death from cardiovascular causes).

Population 17 802 healthy men and women who had low density lipoprotein cholesterol levels of less than 3.4 mmol/L and high sensitivity C reactive protein levels of 2.0 mg/L or more.

Methods Data from the Justification for the Use of Statins in Prevention trial were used to predict rosuvastatin treatment effect for individual patients based on existing risk scores (Framingham and Reynolds) and on a newly developed prediction model. We compared the net benefit of prediction based rosuvastatin treatment (selective treatment of patients whose predicted treatment effect exceeds a decision threshold) with the net benefit of treating either everyone or no one.

Results The median predicted 10 year absolute risk reduction for cardiovascular events was 4.4% (interquartile range 2.6-7.0%) based on the Framingham risk score, 4.2% (2.5-7.1%) based on the Reynolds score, and 3.9% (2.5-6.1%) based on the newly developed model (optimal fit model). Prediction based treatment was associated with more net benefit than treating everyone or no one, provided that the decision threshold was between 2% and 7%, and thus that the number willing to treat (NWT) to prevent one cardiovascular event over 10 years was between 15 and 50.

Conclusions Data from randomised trials can be used to predict treatment effect in terms of absolute risk reduction for individual patients, based on a newly developed model or, if available, existing risk scores. The value of such prediction of treatment effect for medical decision making is conditional on the NWT to prevent one outcome event.

Trial registration number Clinicaltrials.gov NCT00239681.

Footnotes

  • Contributors: JAND designed and carried out the data analyses, interpreted the results, and drafted the manuscript. FLJV conceived the research question, designed the data analyses, interpreted the results, and revised the manuscript for important intellectual content. PMR conceived the research question, collected the data, designed the data analyses, interpreted the results, revised the manuscript for important intellectual content, and is guarantor for the validity of the data and analyses. AMJW and NPP designed the data analyses, interpreted the results, and revised the manuscript for important intellectual content. EWS and YvdG conceived the research question, designed the data analyses, interpreted the results, and revised the manuscript for important intellectual content. NRC conceived the research question, collected the data, designed the data analyses, interpreted the results, and revised the manuscript for important intellectual content.

  • Funding: The Justification for the Use of Statins in Prevention was an investigator initiated trial. The sponsor of the study collected the trial data and monitored the study sites but had no role in the conduct of the analyses or drafting of the report. All statistical analyses were done by the investigators.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: PMR is the principal investigator of the investigator initiated Justification for the Use of Statins in Prevention trial, which was funded by AstraZeneca (Wilmington, Delaware). PMR received grant support from Novartis and Roche; consulting fees from Siemens Medical Systems, ISIS, and Vascular Biogenetics; and is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to Siemens Medical Systems (Erlangen, Germany) and AstraZeneca. FLJV’s department receives grant support from Merck, the Netherlands Organisation for Health Research and Development, and the Catharijne Foundation Utrecht; and speaker fees from Merck and AstraZeneca. JAND, AMJW, NPP, EWS, YvdG, and NRC have no relationships with industry that might have an interest in the submitted work in the previous three years. All authors have no non-financial interests that may be relevant to the submitted work.

  • Ethical approval: The protocol for the Justification for the Use of Statins in Prevention trial was approved by the local institutional review boards at each participating centre. All study participants provided written informed consent before taking part.

  • Data sharing: No additional data available.

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