Abstract

Economic analyses in health technology assessment
often require estimation of absolute risk difference (ARD)
for outcomes such as survival or progression, given base risk in
the jurisdiction of interest and trial evidence of treatment effects.
We demonstrate that odds ratios (OR) provide distinct advantages
over relative risk (RR) in consistently estimating such ARD
independent of the framing of effects (e.g. mortality or survival)
for direct and indirect comparisons. METHODS: Use of RR is
shown to lead to inferential anomalies in estimating ARD, while
consistently estimated using OR. These inferential anomalies and
odds solution are illustrated for indirect comparison of Natiluzimab
versus Interferon beta1b for multiple sclerosis, as well as
direct comparisons. RESULTS: Standard use of relative risk to
calculate ARD in indirect comparison suggests Natiluzimab is
more effective than Interferon for progression (RR = 0.70, ARD
= 21% for a base risk of 70% progression) but less effective than
Interferon for no progression (RR = 0.84, ARD = 4.8%). This inferential anomaly is avoided using OR, with odds of progression
(0.83) the reciprocal of that for no progression (1.21), and
ARD of 4.1% in favor of Nataluzimab with progression or no
progression. For direct comparisons ARD is shown to be consistently
estimated with OR but change with framing of effects
using RR wherever epidemiological risk differs from trial risk in
the comparator arm. CONCLUSIONS: Odds ratios allow consistent
estimation of absolute risk differences regardless of
framing of effects in direct and indirect comparisons. This overcomes
inferential anomalies that arise with use of relative risk in
such comparisons whenever base risk differs in the jurisdiction of
interest from that in trials, or base risk in the common arms
differs in indirect comparisons. Consequently, odds ratios avoid
selection biases in framing of effects inherent with risk ratios and
are suggested as the preferred metric in estimating such risk
differences.