Association of Patient Belief About Success of Antibiotics for Appendicitis and Outcomes: A Secondary Analysis of the CODA Randomized Clinical Trial

Abstract

Importance: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials.

Objective: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial.

Design, setting, and participants: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis.

Interventions: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful.

Main outcomes and measures: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors.

Results: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13-percentage point lower risk of appendectomy (aRD, -13.49; 95% CI, -24.57 to -2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was -5.68 (95% CI, -16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, -15.72; 95% CI, -29.71 to -1.72), with directionally similar results for the completely successful group (aRD, -15.14; 95% CI, -30.56 to 0.28).

Conclusions and relevance: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation.

Trial registration: ClinicalTrials.gov Identifier: NCT02800785.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Voldal reported receiving grants from the Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study. Dr Liao reported receiving personal fees from Kaiser Permanente Washington Health Research Institute; honoraria from Wolters Kluwer, the Journal of Clinical Pathways, and the American College of Physicians; and grants from the National Institute of Aging all outside of this submitted work. Dr Thompson reported serving as a reviewer for the Shriner’s Research Fund and receiving personal fees from UpToDate. Dr Self reported receiving grants from PCORI during the conduct of the study. Dr Price reported having an association with Kerecis as a key opinion leader, Acera for research and a key opinion leader, and Medline for research and as a key opinion leader. Dr D. Evans reported receiving consulting fees from Tetraphase, consulting and speaking fees from Fresenius Kabi, and consulting and speaking fees from Abbott Laboratories outside the submitted work. Dr H. Evans reported receiving personal fees from Tetraphase outside the submitted work. Dr Faine reported receiving grants from Spero Therapeutics outside the submitted work. Dr Neufeld reported receiving grants from the National Institutes of Health outside the submitted work. Drs Heagerty, Monsell, Fannon, Kessler, and Flum reported receiving grants from PCORI during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Cumulative Incidence of Appendectomy After Being Randomly Assigned to Antibiotics, by Belief Group

Shaded regions correspond to 95% CIs. Cumulative incidence (95% CI) and number of participants still at risk for an appendectomy are shown at 48 hours and 30 days after randomization for each belief group. Ten participants were excluded from this figure for missing data on belief.

Figure 2.. Association Between Belief and Appendectomy Within 30 Days With 95% CIs

Estimates are pooled from multiply imputed data sets. Baseline factors accounted for in the adjusted risk differences (RDs) were age, sex, body mass index, race, Hispanic ethnicity, health literacy help, education, low income or Medicaid/state program, average pain in the previous 7 days, appendiceal diameter, and appendicolith. Information on appendectomy status at 30 days was missing for 14 participants (eAppendix 4 in Supplement 3 for counts from complete case data).

Figure 3.. Association Between Belief and Signs or Symptoms of Appendicitis Up to 30 Days With 95% CIs

Estimates are pooled from multiply imputed data sets. Baseline factors accounted for in the adjusted risk differences (RDs) were age, sex, body mass index, race, Hispanic ethnicity, health literacy help, education, low income or Medicaid/state program, average pain in the previous 7 days, appendiceal diameter, and appendicolith. Information on persistent signs and symptoms at 30 days was missing for 41 participants (eAppendix 4 in Supplement 3 for counts from complete case data).

Figure 4.. Association Between Belief and High Regret or Dissatisfaction at 30 Days With 95% CIs

Estimates are pooled from multiply imputed data sets. Baseline factors accounted for in the adjusted risk differences (RDs) were age, sex, body mass index, race, Hispanic ethnicity, health literacy help, education, low income or Medicaid/state program, average pain in the previous 7 days, appendiceal diameter, and appendicolith. Information on regret or dissatisfaction at 30 days was missing for 50 participants (eAppendix 4 in Supplement 3 for counts from complete case data).