An Evaluation of Different Strategies for Sampling Controls in an Online Case-Crossover Study of Acute Flares in Knee Osteoarthritis

Abstract

Objective

To evaluate bias and precision of exposure-outcome effect estimates from three control sampling strategies in a case-crossover study.

Methods

Online case-crossover study investigating eight physical activity-related triggers for acute flares in knee osteoarthritis. Exposures were measured in hazard periods (≤24 hours before self-declared flare onset). Control period exposure was measured in three ways: (1) four scheduled questionnaires over 13-weeks, (2) “usual” physical activity levels ascertained at baseline, (3) over three days before flare onset. Derived odds ratios, 95% confidence intervals and standard errors were compared.

Results

Of 744 participants (mean age 62.1 [SD 10.2] years; 61% female), 493 reported 714 flares. Selecting controls from scheduled questionnaires, independent of hazard periods, yielded predominantly odds ratios in the expected direction (exposure “a lot” versus exposure “not at all”, range: 0.57–3.22). When controls were sampled at baseline (range: 0.01–1.42) or immediately before a flare (range: 0.30–1.27) most odds ratio estimates were inverted. Standard errors of the log odds ratios were smallest when controls were sampled from scheduled questionnaires (range: 0.264–0.473) compared to controls sampled at baseline (range: 0.267–0.589) or immediately before a flare (range: 0.319–0.621).

Conclusion

Our findings are sensitive to control sample selection. Under certain conditions, different patterns could be attributed to over reporting and social desirability bias, where people may want to present themselves more positively about their “usual” physical activity levels, at baseline. Exposure measurement at the time of a flare may be less precise and more susceptible to recall bias due to systematically reporting exposures differently during a flare, compared to control measurement independent of flares.

Keywords:

• osteoarthritis
• flare
• pain
• case-crossover
• sampling
• knee

Data Sharing Statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethics Approval and Informed Consent

All study procedures were compliant with the Declaration of Helsinki. Ethical approval was obtained from Yorkshire & The Humber-Leeds East Research Ethics Committee (REC reference number: 18/YH/0075). Informed consent to participate was obtained from all participants.

Disclosure

Professor George Peat reports grants from Primary Care Centre Versus Arthritis, during the conduct of the study. Professor Tuhina Neogi reports grants, consultant for Pfizer/Lilly, Novartis, and Regeneron, outside the submitted work. Dr Martin J Thomas reports grants from National Institute for Health and Care Research/Health Education England, during the conduct of the study. The authors report no other conflicts of interest in this work.

Additional information

Funding

Tuhina Neogi was supported by NIH K24 AR070892 and NIH P30 072571. Martin J Thomas was funded by a National Institute for Health and Care Research (NIHR) and Health Education England (HEE) Integrated Clinical Academic Programme Clinical Lectureship (ICA-CL-2016-02-014) for this project and an NIHR Development and Skills Enhancement Award (NIHR300818). This publication presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, HEE or the Department of Health and Social Care. For the purposes of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.