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Table 3 Summary of findings

From: Adherence to breast cancer guidelines is associated with better survival outcomes: a systematic review and meta-analysis of observational studies in EU countries

Outcomes

№ of participants (studies) Follow-up

Certainty of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Non-adherence to CG*

Risk difference with adherence to CG

Overall survival assessed with: adjusted hazard ratio follow up: median 60 monthsa

15,974 (4 non-randomised studies) [17, 40, 49, 50]

MODERATE a,b

HR 0.67 (0.59 to 0.76) [death]

431 per 1.000 c

138 more per 1.000 (96 more to 178)

Disease free survival assessed with: adjusted hazard ratio follow up: median 60 monthsa

9224 (3 non-randomised studies) [36, 49, 50]

LOW a,b,d

HR 0.35 (0.15 to 0.82) [recurrence]

370 per 1.000 e

336 more per 1.000 (73 moreto 491 more)

Treatment costsf

(1 observational study) [39]

LOW f,

Higher costs for treatment concordant to CG.

Follow-up costsf

(1 observational study) [38]

LOW f,

Non-CGs adherent follow-up was 2.2 to 3.6 times more expensive than the compliant one [5, 7].

  1. *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
  2. CI Confidence interval, HR Hazard Ratio
  3. a) To assess this outcome we considered adherence to clinical guidelines as a prognosis factor for survival related outcomes. According to GRADE guidance for the assessment of prognosis clinical questions, observational studies are the main source of evidence, and have to potential to provide a high level of certainty. However, the optimal study design for prognosis questions are high quality prospective cohort studies. Although all the included studies used regression analyses to adjust for most important confounding clinical variables, we rated down our confidence in effects due concerns of serious risk of bias related with the study design (all selected studies were retrospective cohorts based on medical records or hospital database registries)
  4. b) Despite the existence of important differences across studies both in terms of the context of application, and of the conceptualisation of adherence applied, we did not rate down for indirectness, as results were highly consistent across different contexts and definitions
  5. c) The mortality rate in the group not receiving CG adherent treatment was 43.14% (1477/3424)
  6. d) We rated down one level our confidence in effects due to the high level of unexplained heterogeneity (I2: 96%). However, it should be noted that in the context of guideline development, it may not be appropriate to rate down for heterogeneity, since the desirable effects are highly consistent across studies
  7. e) Th recurrence rate in the group not receiving CG adherent treatment was 37% (578 / 1553)
  8. f) To assess the impact of adherence on costs we used an intervention (rather than a prognosis) approach, since cost is not a clinical outcome and the objective of this assessment was to examine a potential causal relationship. For this reason, the certainty of evidence was rated as “low”, as only observational studies were available
  9. GRADE Working Group grades of evidence
  10. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
  11. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
  12. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
  13. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect