USING NET BENEFITS AND ACCEPTABILITY CURVES TO QUANTIFY UNCERTAINTY ABOUT TRADEOFFS BETWEEN HARMS AND BENEFITS OF ORAL CONTRACEPTIVES

Purpose: To explore the potential application of net benefits (NB) and acceptability curves using outcomes other than cost-effectiveness

Method: We developed a model to estimate the impact of oral contraceptives (OCs) on potentially fatal non-reproductive outcomes.     Potential harms included increased risk of vascular events (deep venous thrombosis, pulmonary embolism, stroke, and myocardial infarction) and some cancers (breast cancer and cervical cancer).   Potential benefits included reduced risk of ovarian, colorectal, and endometrial cancers.    The model simulated a cohort of US women from age 10 through 100.    All probabilities were stratified by age, race/ethnicity, and BRCA1/BRCA2 status where possible.   Population-based incidence and mortality for all outcomes were estimated from population-based datasets.    Probabilities of contraceptive method usage were derived from the National Survey of Family Growth.    Relative risk estimates for each outcome conditional on OC use were derived from a series of systematic reviews and random effects meta-analyses, and subsequently used to estimate incidence in users and non users.  All parameters were defined as distributions based on the available data and the parameter type.     We performed a series of microsimuations, including a two-dimensional analysis consisting of an outer loop of 200 draws from the relative risk estimates, with 10,000 simulated subjects per draw, and estimated lifetime incidence and mortality for each outcome with and without OC use.     We defined willingness-to-pay (WTP) as the maximum acceptable ratio of harms to benefits attributable to OC use, and calculated NB for OC use and nonuse using the formula

NB=(WTP*Benefits) - Harms  We created acceptability curves by graphing the proportion of simulations where OC use resulted in a higher NB at different WTP values, then sequentially removing specific harms and benefits from the NB equation. 

Result: Although estimated incidence of both vascular events and breast and cervical cancer was increased with OC use, breast cancer was the greatest contributor to uncertainty about mortality trade-offs (Figure), because of effects of OC use on age-specific incidence and subsequent cause-specific mortality.

Conclusion: NB and acceptability curves can be used to convey uncertainty about trade-offs between specific harms and benefits at different thresholds and may be particularly useful in developing evidence-based guidelines using systems such as GRADE.