Research

Monitoring adherence to drug treatment by using change in cholesterol concentration: secondary analysis of trial data

BMJ 2011; 342 doi: 10.1136/bmj.d12 (Published 21 January 2011)
Cite this as: BMJ 2011;342:d12
  1. Katy J L Bell, research academic1,
  2. Adrienne Kirby, biostatistician2,
  3. Andrew Hayen, senior lecturer, biostatistics1,
  4. Les Irwig, professor of epidemiology1,
  5. Paul Glasziou, director3
  1. 1Screening and Test Evaluation Program (STEP), School of Public Health, University of Sydney, NSW 2006, Australia
  2. 2NHMRC Clinical Trials Centre, University of Sydney
  3. 3Centre for Research in Evidence Based Practice, Bond University, QLD 4229, Australia
  1. Correspondence to: A Hayen andrew.hayen{at}sydney.edu.au
  • Accepted 13 October 2010

Abstract

Objective To estimate the accuracy of monitoring cholesterol concentration for detecting non-adherence to lipid lowering treatment.

Design Secondary analysis of data on cholesterol concentration in the LIPID (long term intervention with pravastatin in ischaemic disease) study by using three measures of non-adherence: discontinuation of treatment, allocation to placebo arm, less than 80% of pills taken.

Setting Randomised placebo controlled trial in Australia and New Zealand.

Participants 9014 patients with previous coronary heart disease.

Interventions Pravastatin 40 mg or placebo daily.

Main outcome measures Sensitivity, specificity, area under the receiver operating characteristics (ROC) curve, post-test probability.

Results Monitoring of cholesterol concentration had modest ability for detecting complete non-adherence. One year after the start of treatment, half (1957/3937) of the non-adherent patients and 6% (253/3944) of adherent patients had a rise in concentration of low density lipoprotein cholesterol. Accuracy was reasonable (area under the curve 0.89). Cholesterol monitoring, however, had weak ability for detecting partial non-adherence. One year after the start of treatment, 16% (34/213) of partially adherent and 4% (155/3585) of fully adherent patients had a rise in concentration of low density lipoprotein cholesterol. Accuracy was poor (area under the curve 0.65). For typical pre-test probabilities of non-adherence ranging from low (25%) to high (75%), the post-test probabilities indicate continuing uncertainty after lipid testing. A patient with no change in low density lipoprotein cholesterol concentration has a post-test probability of being completely non-adherent of between 67% and 95% and a post-test probability of being partially non-adherent of between 48% and 89%. A patient with a decrease in concentration of 1.0 mmol/L has a post-test probability of being completely non-adherent of between 7% and 40% and a post-test probability of being partially non-adherent of between 21% and 71%.

Conclusions Monitoring concentration of low density lipoprotein (or total) cholesterol has modest ability to detect complete non-adherence or non-persistence with pravastatin treatment and weak ability to detect partial non-adherence. Results of monitoring should be considered as no more than an adjunct to careful discussion with patients about adherence.

Footnotes

  • Contributors: KJLB drafted and revised the manuscript and contributed to the concept, design, and analysis and interpretation of data. AK did the statistical analysis and contributed to the acquisition of data and revision of the manuscript. AH assisted in the statistical analysis and contributed to the concept, design, interpretation of data, and revision of the manuscript. LI obtained funding and contributed to the concept, design, analysis and interpretation of data, and revision of the manuscript. PG contributed to the concept, design, acquisition of data, analysis and interpretation of data, and revision of the manuscript. AK is guarantor.

  • Funding: The authors have received funding from the Australian National Health and Medical Research Council (Program Grant No 402764). The LIPID trial was supported by a grant from the Bristol-Myers Squibb Pharmaceutical Research Institute and conducted under the auspices of the National Heart Foundation of Australia. The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three year, no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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