Forgiveness is the attribute of the strong: nonadherence and regimen-shortening in drug-sensitive TB

Helen R Stagg*, Jennifer A Thompson, Marc C I Lipman, Derek J Sloan, Mary Flook, Katherine L Fielding

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Rationale: ‘Forgiveness’ charts the ability of a drug or regimen to withstand non-adherence without negative clinical consequences.

Objectives: We aimed to determine the influence of regimen length, regimen drugs and dosing, and when during treatment non-adherence occurs on the forgiveness of anti-tuberculosis regimens.

Methods: Using data from three randomised controlled trials comparing experimental four-month regimens for drug-sensitive tuberculosis with the standard six-month regimen, we used generalised linear models to examine how the risk of a negative composite outcome changed as dose-taking decreased. The percentage of doses taken and absolute number of doses missed were calculated, during the intensive and continuation phases of treatment, and overall. A mediation analysis was undertaken to determine how much of the association between intensive phase dose-taking and the negative composite outcome was mediated through continuation phase dose-taking.

Measurements and Main Results: Forgiveness of the four-month and six-month regimens did not differ for any treatment period. Importantly, four-month regimens were no less forgiving of small numbers of absolute missed doses than the six-month regimen (e.g. for 3-7 missed doses versus no missed doses (baseline), six-month regimen adjusted risk ratio 1.65 (95% confidence interval 0.80-3.41) and four-month regimens 1.80 (1.33-2.45)). No four-month regimen was conclusively more forgiving than another. We found evidence of mediation by continuation phase dose-taking on the intensive phase dose-taking and negative composite outcome relationship.

Conclusions: With the current appetite for, and progress towards, shorter drug-sensitive tuberculosis regimens worldwide, we offer reassurance that shorter regimens are not necessarily less forgiving of non-adherence. Given the importance of continuation phase adherence, patient support during this period should not be neglected.
Original languageEnglish
Pages (from-to)193-205
Number of pages13
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number2
Publication statusPublished - 15 Jan 2023


  • Tuberculosis
  • Forgiveness
  • Adherence
  • Non-adherence
  • Treatment


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