Potential Cost-Effectiveness of Prenatal Distribution of Misoprostol for Prevention of Postpartum Hemorrhage in Uganda

<div><p>Background</p><p>In settings where home birth rates are high, prenatal distribution of misoprostol has been advocated as a strategy to increase access to uterotonics during the third stage of labor to prevent postpartum hemorrhage (PPH). Our objective was to project the potential cost-effectiveness of this strategy in Uganda from both governmental (the relevant payer) and modified societal perspectives.</p><p>Methods and Findings</p><p>To compare prenatal misoprostol distribution to status quo (no misoprostol distribution), we developed a decision analytic model that tracked the delivery pathways of a cohort of pregnant women from the prenatal period, labor to delivery without complications or delivery with PPH, and successful treatment or death. Delivery pathway parameters were derived from the Uganda Demographic and Health Survey. Incidence of PPH, treatment efficacy, adverse event and case fatality rates, access to misoprostol, and health resource use and cost data were obtained from published literature and supplemented with expert opinion where necessary. We computed the expected incidence of PPH, mortality, disability adjusted life years (DALYs), costs and incremental cost effectiveness ratios (ICERs). We conducted univariate and probabilistic sensitivity analyses to examine robustness of our results. In the base-case analysis, misoprostol distribution lowered the expected incidence of PPH by 1.0% (95% credibility interval (CrI): 0.55%, 1.95%), mortality by 0.08% (95% CrI: 0.04%, 0.13%) and DALYs by 0.02 (95% CrI: 0.01, 0.03). Mean costs were higher with prenatal misoprostol distribution from governmental by US$3.3 (95$1.3; 95% CrI: -1.6, 2.8) perspectives. ICERs were US$191 (95$73 (95% CI: -86, 256) per DALY averted from a modified societal perspective.</p><p>Conclusions</p><p>Prenatal distribution of misoprostol is potentially cost-effective in Uganda and should be considered for national-level scale up for prevention of PPH.</p></div

Results of the cost-effectiveness analysis (cost per life saved and cost per DALYs averted).

<p>Values in brackets are 95% Credibility Intervals for incremental costs and outcomes from the PSA.</p

Probabilities of PPH, treatment efficacy of uterotonics and case fatality rate of PPH.

<p>^a Computed by multiplying the baseline probability of PPH in unskilled delivery by the ratio of the relative risk of PPH comparing active to expectant management of the third stage of labor</p><p>^b A random effects meta-analysis of incidence of PPH in the non-interventional arms of clinical studies comparing a uterotonic to no uterotonic</p><p>^c A random effects meta-analysis of trials that compared the risk of PPH with misoprostol versus placebo in a setting of skilled assistance at delivery</p><p>Probabilities of PPH, treatment efficacy of uterotonics and case fatality rate of PPH.</p

Parameters to compute a woman’s probable delivery pathway trajectory: base case probabilities (sensitivity ranges) by wealth quintile, UDHS 2011[5].

<p>¹ conditioned on wealth quintile</p><p>² conditioned on delivery in health facility</p><p>³ Joint probabilities of non-health facility delivery and either unassisted or assisted by TBA</p><p>^†TBA = Traditional Birth Attendant</p><p>Parameters to compute a woman’s probable delivery pathway trajectory: base case probabilities (sensitivity ranges) by wealth quintile, UDHS 2011[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142550#pone.0142550.ref005" target="_blank">5</a>].</p

Tornado diagram of univariate sensitivity analysis.

<p>The diagram shows the impact of the 10 most influential parameters on the incremental cost per DALY averted from a modified societal perspective</p

Decision tree showing the delivery pathway trajectory and outcomes considered in the analysis.

<p>The delivery pathway trajectory i.e., place of delivery (health facility versus non-health facility birth) and assistance at delivery (skilled assistance, traditional birth attendant, relative or friend and unassisted delivery) is defined by wealth quintile from the Uganda Demographic and Health Survey. We follow women through to the immediate postpartum period in which they may receive prophylactic uterotonics (or not), may experience postpartum hemorrhage (or not), may access emergency obstetric care or not and may recover or die due to postpartum hemorrhage. We allow access to emergency obstetric care to vary by delivery pathway. Further, we account for the potential of misoprostol misuse through stillbirth or uterine rupture outcomes. This model structure is used to project the costs and outcomes (incident postpartum hemorrhage, mortality due to postpartum hemorrhage and disability adjusted life years) of a cohort of pregnant women in Uganda.</p

Tornado diagram of univariate sensitivity analysis.

<p>The diagram shows the impact of the 10 most influential parameters on the incremental cost per DALY averted from a governmental perspective</p

Probabilities of receiving uterotonics and probabilities of accessing emergency obstetric care by delivery pathway trajectory.

<p>Probabilities of receiving uterotonics and probabilities of accessing emergency obstetric care by delivery pathway trajectory.</p

Incremental cost-effectiveness scatter plot showing the distribution of 10,000 incremental cost and DALY averted pairs.

<p>The green cloud shows the analysis from the governmental perspective and the purple cloud shows the analysis from the modified societal perspective. The dashed red line represents the lower threshold of willingness to pay per DALY averted (one times the GDP of Uganda) and the solid red line represents the higher threshold of willingness to pay per DALY averted (three times the GDP of Uganda).</p

Distribution of blood loss and hemoglobin change by treatment arm.

<p>(A) Distribution of blood loss by treatment arm. (B) Change in hemoglobin during hospitalization by treatment arm.</p