key: cord-0809878-yl5kc249 authors: Hunter, Caitlin; Jensen, Joshua; Imeah, Biaka; McCarron, Michelle; Clark, Megan title: A retrospective cost-effectiveness analysis of mifepristone-misoprostol medical abortions in the first year at the Regina General Hospital date: 2020-08-25 journal: J Obstet Gynaecol Can DOI: 10.1016/j.jogc.2020.08.008 sha: 466d5e86b080ab1c2b10b9ba1f272c0c0b10bbfd doc_id: 809878 cord_uid: yl5kc249 Abstract Objective In July 2017, mifepristone–misoprostol (mife/miso) became available for medical abortion at the Regina General Hospital's Women's Health Centre (RGH WHC). We investigated whether the proportion of abortions performed medically changed as a result of the introduction of mife/miso, whether using mife/miso instead of the surgical alternative would result in cost savings to the health care system, and whether abortion type differed between patients residing in and outside of Regina. Methods We conducted a retrospective chart review of all 306 medical abortions from the RGH WHC between July 1, 2017 and June 30, 2018. We obtained medical and surgical abortion information from that year and the preceding one from an administrative database. Statistical methods were used to calculate the costs of mife/miso, methotrexate-misoprostol (MTX/miso) and surgical abortion, as well as cost-effectiveness ratios. Results The proportion of medical abortions increased from 15.4% in 2016/2017 to 28.7% in 2017/2018 (χ2 1 =54.629; P < 0.001). Calculated costs for mife/miso, with and without complications were CAN$1173.70 and CAN$1708.90, respectively, versus CAN$871.10 and CAN$1204.10, respectively, for MTX/miso, and CAN$1445.95 and CAN$2261.95, respectively, for hospital-based vacuum aspiration. At a willingness-to-pay threshold of CAN$318 (the cost of mife/miso), statistical modelling showed a 61.3% chance that mife/miso was more cost-effective than surgical abortion and a 90.8% chance that it was more cost-effective than MTX/miso. Patients from Regina were significantly more likely (χ2 1 =29.406; P < 0.001) to receive a medical abortion (34.9% of abortions) than those living outside of Regina (19.6% of abortions). Conclusion The proportion of abortions completed medically increased significantly over the period studied. Patients from Regina were more likely to receive medical abortion during both time periods. Mife/miso had a >50% probability of cost-effectiveness over both surgical and MTX/miso options. The proportion of abortions completed medically increased significantly over the period studied. Patients from Regina were more likely to receive medical abortion during both time periods. Mife/miso had a >50% probability of cost-effectiveness over both surgical and MTX/miso options. Objectif : En juillet 2017, la combinaison mifépristone-misoprostol a été rendue disponible aux fins d'avortement médicamenteux au centre de santé des femmes du Regina General Hospital. Nous avons tenté de déterminer si l'arrivée de la mifépristone-misoprostol avait eu une incidence sur la proportion d'avortements médicamenteux, si le recours à la mifépristone-misoprostol plutôt qu'à l'avortement chirurgical allait engendrer des économies pour le système de santé, et si le type (le coût de la mifépristone-misprostol), le modèle statistique a révélé que la mifépristone-misprostol avait Over the last 10 years, approximately 100,000 elective terminations of pregnancy have occurred annually in Canada [1] . Nearly one-third of Canadian women have at least one abortion [2] . In 2015, Health Canada approved the use of mifepristone plus misoprostol (mife/miso; Canadian brand name Mifegymiso™, manufactured by Celopharma), both World Health Organization essential medicines, for medical abortion. The less effective off-label regimen of methotrexate plus misoprostol (MTX/miso) was previously used [3] . Until July 2017, this off-label regimen was only used for gestational age (GA) ≤7 weeks and 0 days (7w0d), according to local practice and not SOGC nor National Abortion Federation (NAF) guidelines [3, 29] , at the Regina General Hospital Women's Health Centre (RGH WHC), the main abortion facility and only surgical termination centre for southern Saskatchewan, which performs 900 to 1,100 abortions annually. Mife/miso is safe, effective, and generally considered acceptable by patients and providers [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] . It is 95-98% effective to 49 days after last menstrual period (LMP), 87-98% effective to 63 days [3, 5, [7] [8] [9] [10] , and there is emerging evidence of safety and efficacy up to 77 days [3, [11] [12] [13] 34 ]. The first Canadian retrospective case series of mife/miso implementation found 96.7% effectiveness up to 63 days GA [14] . Beyond being considered safe and effective, patients receiving medical abortions (of various regimens) are satisfied with their experience [15, 16] . Some studies show a strong preference for medical abortion [15, 17] while others indicate that surgical is preferable [18] [19] [20] . Research indicates patients are more satisfied when given the ability to choose their preferred method [3] . While it varies between countries, the percentage of abortions in Canada that were medical (versus surgical) between 2012 and 2017, before mife/miso's availability, ranged from 4.0 to 5.4% [1, 21] . A Canadian estimate of abortion costs (to both the healthcare system and patients) calculated costs of $1233.34 for mife/miso, $1174.81 for MTX/miso, and $1779.08 for hospitalbased vacuum aspiration [35] . In July 2017, mife/miso became available at the RGH WHC. It was initially only covered for patients with some private plans, who fell under Saskatchewan Formulary coverage or First Nations patients with status, with an out-of-pocket cost of $356.90 after July 31, 2017. In March 2018, mife/miso was added to the hospital formulary, making it available free of charge to all patients at the WHC. The study's purpose was to assess the impact of introducing mife/miso at the WHC on both patients and the healthcare system. Our research questions were: 1) What were the success rates, loss to follow-up rates, and complications during the first year of mife/miso administration at the Centre? 2) Was there an increase in the proportion of induced abortions completed medically following the introduction of mife/miso in July 2017? 3) What were the potential cost benefits of using mife/miso rather than vacuum aspiration? Patients were required to self-refer to the RGH WHC. During the study period, the RGH WHC included nine family physicians and one obstetrician who provided medical and surgical abortion services, with one provider working at the clinic per day. Registered nurses discussed pregnancy options at the patient's initial consultation (in-person or by phone). Medical abortion was considered an option for patients ≤9w0d GA by ultrasound, which was expanded from 7w0d after the first month of the study period per Health Canada regulations. Patients were considered ineligible for medical abortion if they had: known ectopic pregnancy, GA >9w0d, molar pregnancy, IUD in situ, expressed ambivalence (less than 6/10 on ambivalence scale), or an inability to complete phone follow-up. Once the patient was deemed eligible, initial dating ultrasound (a Health Canada requirement during the study period) and lab work was ordered, including complete blood count, renal panel, liver enzymes/bilirubin, quantitative serum βhCG, urine chlamydia and gonorrhea screening, and prenatal serology (including HIV, rubella, Hepatitis B/C and syphilis screens). Only CBC and quantitative serum βhCG are recommended in SOGC and NAF medical abortion guidelines [3, 29] ; the rest are local protocol. The physician reviewed these results and prescribed mife/miso (mifepristone 200 mg orally and misoprostol buccally 24 to 48 hours later) directly to the patient at a second in-person appointment. Nurses phoned patients for follow-up; an 80% drop in serum βhCG 7 days post misoprostol administration was considered a complete abortion. All charts were de-identified and entered into a REDCap database [22] . Descriptive statistics and 2x2 Chi-square tests were produced. We utilized a micro-costing (bottom-up) approach from the perspective of the health system, in 2020 Canadian dollars. Since the decision to adopt mife/miso lies with the healthcare system, the economic analysis was performed from their perspective. This approach entails identifying and specifying all the resources utilized by individual patients, assuming resource use being the same across each method of abortion, including medication cost, diagnostic and laboratory services cost, staffing, and supplies (Table 1) . We determined unit costs by collecting drug price data from the Saskatchewan Formulary database[30], expenditure records from diagnostic and laboratory services, physician payment from the Saskatchewan Medical Association (SMA) payment schedule [25] , and other facility expenditure records. We determined complication costs using Canadian Institute for Health Information (CIHI) cost of standard hospital stay and the resource intensity weight for the case mix group for hospital admissions [31] , the cost of a single uncomplicated surgical abortion for repeat vacuum aspiration at WHC, and estimated the cost of anesthesia, physician fees and operating room staffing for repeat vacuum aspiration in the operating room. We did not account for infrastructural cost as this was not collected during microcosting and because of the complexity associated with estimating such cost. The result of the analysis is expressed as an incremental cost-effectiveness ratio (ICER). We set the willingness-to-pay (WTP) threshold, the maximum amount that our payer, the healthcare system, would be willing to pay for one additional complete abortion [32] , at $318, the cost of mife/miso. Effect was measured as success rate, i.e., the proportion of complete abortions for each method. We performed a probabilistic sensitivity analysis to determine the robustness of our result in relation to the uncertainty in cost and effect (success rate) estimations. Instead of specific values for success rate of each abortion method, we chose a uniform distribution, with observed minimum and maximum values as the range of distribution, to reflect uncertainty around our estimate of success rate for each abortion method with equal probability of selection for all values within the specified range. Probability of complete abortion, with minimum and maximum tested based on literature-reported rates, for MTX/miso was between 81.7% and 98% [3] ; for vacuum aspiration (≤9w0d, to compare to the maximum gestation for mife/miso in our study period), between 98% and 99.7% [33] ; and for mife/miso, between 97.7% and 99.7% (upper boundary for vacuum aspiration) [34] . Similarly, we assumed a uniform distribution for examining uncertainty in cost estimation. The cost of a single uncomplicated abortion estimated for each method was the same across patients; we varied this estimate by 10%, an arbitrary number chosen to further examine the uncertainty with regards to this estimate. Total cost estimates for complications were allowed to vary probabilistically within their estimated minimum and maximum intervals. We summarized cost and effectiveness of each abortion method based on 10,000 probabilistic simulations of cost and effects. The analysis was performed using R software. The results are graphed as an incremental cost-effectiveness (CE) plane and cost effectiveness acceptability curve (CEAC) with specified willingness-to-pay (WTP) range. A statistically significant improvement in abortion completion rate was observed when using mife/miso rather than MTX/miso: 98.2% versus 84.1% (χ 2 1 = 23.790, p<0.001; Figure 1) . A total of 20 (6.5%) vacuum aspirations were performed following medical abortion: 4 after mife/miso, 15 after MTX/miso, and 1 after both. The overall mife/miso complication rate was 8.5% (n=20 of 236 with follow-up). Overall, 15 medical abortion patients (4.9%) visited the RGH emergency department. Eleven patients (4.7%) had retained products of conception, two had infections (0.8%), six had significant bleeding noted [26] [27] [28] . We observed rates of complete abortion ≤9w0d with mife/miso of 98.2%, versus 84.1% for MTX/miso and 99.6% after vacuum aspiration. This translated into an incremental effect of 14.80% for mife/miso over MTX/miso, and -1.34% over vacuum aspiration, with costs delineated in Table 1 . Incremental cost for mife/miso relative to using methotrexate is $302 for a single complete abortion without complication, and -$272 versus vacuum aspiration. This demonstrates an increased cost of $302 for a 14.8% increase in effect of mife/miso over MTX/miso. The ICER for mife/miso relative to MTX/miso is $2,149 for a single uncomplicated abortion, and $20,317 for mife/miso versus vacuum aspiration. Similarly, the ICER for mife/miso relative to MTX/miso for a single complicated abortion is $3,585, and $41,272 versus a vacuum aspiration. On the cost-effectiveness (CE) plane for mife/miso relative to MTX/miso (Figure 2 ), the line through the origin represents the set WTP threshold at $318, the estimated price of mife/miso. The CE plane suggests that mife/miso is likely to be more costly and more effective or less costly and more effective than MTX/miso. At $318 WTP, the probability that mife/miso would be costeffective relative to MTX/miso is 90.8%, and 61.4% relative to vacuum aspiration (see Figure 3 , cost-effectiveness acceptability curves [CEAC] ). The proportion of medical abortions increased significantly from 15.4% to 28.7% of all induced abortions at WHC after mife/miso's introduction in July 2017. There was a significant improvement in completion rate when using mife/miso rather than MTX/miso. Our calculated completion rate of mife/miso was 98.2%, comparable to other studies [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] . Patients were more likely to choose mife/miso over MTX/miso after its addition to the hospital's formulary in March 2018, when it was free of charge to all WHC patients. As expected, we found medical abortion to be cheaper than surgical with an ICER suggesting cost-effectiveness. Our loss to follow-up rate of 5.9% was lower than reported rates of 9% to 30% [7, 8, 10, 11, 15, 19] . Our low rate may be a result of requiring quantitative βhCG and phone follow-up versus in-person appointments or ultrasounds. Although previous studies have not found a significant difference in loss to follow-up for remote versus in-clinic visits, one study did find that patients prefer the remote follow-up option [23] . The substantial nursing staff effort, a median of 37.5 minutes of follow-up per medical abortion, could also account for our low rate. Of the 18 patients lost to follow-up, only four were from rural populations. This supports mife/miso as a safe and effective option for rural patients despite potentially challenging follow-up care, as rural patients' loss to follow-up rates were relatively low. Fewer rural patients received a medical abortion than patients from Regina, accounting for approximately one-quarter of such cases. Given that medical abortion is safe and effective for rural patients, province-wide expansion of medical abortion provision is of great importance. Since fall 2018, no physician fee code exists for medical abortion in Saskatchewan. For the expansion of medical abortion to occur, given our calculated median of 37.5 minutes of follow-up per patient, compensation for community family physicians, nurse practitioners, and gynecologists providing this service, especially outside Saskatchewan's two urban surgical abortion centres, Regina and Saskatoon, is necessary. Tele-abortion is another feasible option for expansion. This has been successfully implemented in the United States and other Canadian provinces, such as British Columbia [8, 24] . A provincial centralized nursing line for all Saskatchewan patients would be an efficient and cost-effective way to provide follow-up care for medical abortions. Prior to the COVID-19 pandemic, Regina was the only place in Saskatchewan that offered both nursing pre-abortion consultations and follow-up by phone, which has been expanded during COVID-19 and hopefully will continue afterwards. There were several limitations to our study and our cost-effectiveness analysis. With Health Canada now abolishing the universal ultrasound requirement, costing $276.80, many medical abortions carry an additional cost savings of $276.80. Our calculations also assumed five surgical procedures per WHC clinic, which is often no longer the case with the advent of mife/miso, making staffing resource use higher per surgical procedure. We also assumed physician costs to be the same for both medical and surgical abortion, and Saskatchewan now has no billing code for medical abortion. Surgical abortions may cost less outside our hospital setting. Other important limitations include potentially limited generalizability based on mife/miso's first year at one centre (with extra baseline laboratory tests from NAF and SOGC guidelines) and only accounting for complications that presented to Regina's two hospitals. We found mife/miso's complete abortion rate to be 98.2%, with 5.9% lost to follow-up and 8.5% having complications. The proportion of medical abortions increased significantly with the introduction of mife/miso. Compared to patients from outside Regina, patients from Regina were significantly more likely to receive a medical abortion. At a threshold willingness-to-pay assumption of $318 (the cost of the drug), mife/miso had a >50% chance of increased costeffectiveness over both MTX/miso and surgical options. *In the first case, the patient who received mife/miso and had a 79% decrease in βHCG at the one- week follow-up. There was a rise in the subsequent βHCG, which was ordered per clinic guidelines as an 80% decrease was not seen at one week. She was asymptomatic, but was given methotrexate for query ectopic pregnancy due to rising βHCG. She presented to the emergency department one week later and ultimately decided to have a vacuum aspiration, which was complete. The second patient had a pregnancy of unknown location on ultrasound with a GA of 7 weeks by LMP. She was given mifepristone, but had rising βHCG on follow-up. Repeat ultrasound at that time indicated a true or pseudogestational sac measuring 5 weeks GA. Methotrexate was given at that time, which resulted in complete abortion. 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Saskatoon Star Phoenix Mifegymiso cost analysis to be considered in Sask. universal coverage review. Global News Regina To provide universal coverage for abortion pill Mifegymiso. CBC Saskatchewan National Abortion Federation. 2020 clinical policy guidelines Drug Plan and Extended Benefits Branch Canadian Institute of Health Information System Methods for the economic evaluation of health care programmes A non-inferiority study of outpatient mifepristonemisoprostol medical abortion at 64-70 days and 71-77 days of gestation Early abortion in Ontario: options and costs We would like to thank the Women's Health Centre staff at Regina General Hospital, especially Unit Coordinator, Karen Fillmore, and Manager, Jacki Shannon. We would also thank the Health