Computational protocol: Nurse versus physician-provision of early medical abortion in Mexico: a randomized controlled non-inferiority trial

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Protocol publication

[…] We conducted a randomized controlled non-inferiority trial between November 2012 and January 2013 at two Mexico City Ministry of Health abortion clinics and one hospital. Mean numbers of both medical and surgical abortions performed weekly are 137 and 27 at the clinics and 48 at the hospital, representing 50% of legal abortion provision in Mexico City, a city of 8 851 080 people.We assumed that physicians and nurses would achieve a 95% completion rate for medical abortions, based on a previous randomized controlled trial and a meta-analysis on medical abortion efficacy which found successful medical abortion rates using the mifepristone-misoprostol regimen between 91% to 96% depending on gestational duration. We assumed a 5% non-inferiority margin based on cost-effectiveness and clinical differences – such as the ability of nurses and physicians to determine gestational duration, screen for early medical abortion and determine incomplete abortion. We used the PASS software version 11 (NCSS, LCC, Kaysville, United States of America) to determine that a sample size of 800 (400 per arm) would be sufficient to detect non-inferiority with 90% power and a one-sided significance level of 0.025, assuming 15% loss to follow-up per arm.The study protocol was approved by the Mexico City Ministry of Health and Mexico’s National Institute of Public Health institutional review boards. Ethical approval was obtained from the World Health Organization’s (WHO’s) ethics review committee. We invited experts in medical abortion, nursing, ultrasound training and health systems to participate in a scientific advisory and data safety monitoring committee.The Mexico City Ministry of Health granted temporary permission for nurses to administer medical abortion for study purposes and providers were recruited from existing Ministry of Health personnel. We only recruited physicians who had recently joined clinic staff and who had never provided medical abortion or had only previously managed medical abortion under supervision to minimize unfair comparison between physicians with previous experience and nurses with no experience.Physicians and nurses received separately one and a half weeks of training on medical abortion management. The training was provided by a certified ultrasonographer and one of the authors. To reach a professional level of ultrasound skill,, all physicians and nurses received 20 hours of abdominal and transvaginal ultrasound training using a Hitachi SSD-3500SX console. The providers were certified by experienced obstetricians to have achieved required competency. At each site, an experienced obstetrician – not part of the study – was made available for providers to consult as needed.Women visiting the facilities for an abortion were shown to a private space and screened for eligibility by a nurse participating in the study. Women were invited to participate if they: wanted a medical abortion, were aged 18 years or older, reported a last menstrual period of less than 70 days previously and were willing to provide contact information for follow-up. They were excluded if they had a history of allergy to mifepristone or misoprostol, chronic systemic corticosteroid use, chronic adrenal failure, coagulopathy or current therapy with anticoagulants, inherited porphyria, chronic medical conditions including pre-existing heart, severe hepatic or renal disease and severe anaemia. They were also excluded if they had previously received a medical abortion as part of the Mexico City legal abortion programme. All women were given an opportunity to ask questions before providing written consent. Participants could voluntarily withdraw from the study at any time and for any reason without change to the care they received. Before randomization, enrolled participants provided contact and sociodemographic information via a structured interview.We generated a list of consecutive identification numbers and randomly allocated a physician or a nurse that should provide medical abortion to each number using R 3.1.2 software for Windows (R Foundation for Statistical Computing, Vienna, Austria). As women were recruited, they were assigned an identification number. Allocation was concealed in a sealed envelope, which was only opened once the participant was considered eligible and consented to enrol.All enrolled women received clinical care and medical abortion at their first visit. This included a vaginal and pelvic exam, and an abdominal ultrasound to confirm intrauterine pregnancy and gestational duration. According to Mexico City Ministry of Health guidelines, providers must confirm gestational duration via abdominal ultrasound. Providers followed the guidelines’ standard of care regarding ultrasound image interpretation. Women with an inserted intrauterine device (IUD) that could not be removed before administering mifepristone were excluded from the study. If providers could not confirm gestational duration or intrauterine pregnancy, women were referred to another facility for a β-hCG (human chorionic gonadotropin) fraction test. Since we could not ensure their return to the study, they were excluded.We used the medical abortion regimen recommended by Mexico City Ministry of Health, which differs from WHO’s recommendation. Pregnant women with a gestational duration determined as less than 70 days were given 200 mg of oral mifepristone under supervision followed by instructions to self–administer four tablets of misoprostol (200 μg each) buccally at home, 24 hours later.All women received misoprostol, instructions for administration and contraceptive method counselling from their assigned provider. The study followed the standard of care in counselling and providers offered a mix of different contraceptive methods. Participants were also given an instruction card for contacting a study representative in the event of any questions or concerns and a pamphlet explaining expected side-effects and symptoms that may warrant prompt medical attention – such as heavy bleeding, fever, headache and abnormal vaginal discharge. Women were instructed to return to the clinic for follow-up 7–15 days later.At the follow-up visit, providers confirmed completed abortion based on a clinical symptoms checklist, bleeding history and ultrasound results. If the provider determined that the woman had an ongoing pregnancy or incomplete abortion –such as continued bleeding, tissue residue or cramps – participants were offered an additional 800 μg of misoprostol administered at the clinic or hospital, according to Mexico City Ministry of Health practice. If women requested a manual vacuum aspiration or the provider felt it was warranted – due to remaining fetal tissue, persistent gestational sac or continuation of pregnancy – it was provided on-site by an obstetrician who was not part of the study. Participants who chose to take an additional 800 μg of misoprostol were instructed to return in 7–15 days. If these women still did not have a complete abortion at the second follow-up, a vacuum aspiration was performed on-site, that day.During follow-up, providers asked participants if they had chosen a post-abortion contraceptive method based on the previous counselling. If available, the method was provided; if not, information on where to obtain it was given.All adverse and serious adverse events were recorded by providers using a review form that had been reviewed by the scientific advisory and data safety monitoring committee. Events were recorded and analysed to allow for safety reporting.To assess if there were any significant differences between the two study arms, student’s t-tests and χ2 tests for two independent samples were used. Non-inferiority was tested using intention-to-treat and per-protocol analysis. A 95% confidence interval (CI) for the difference between the physicians’ and nurses’ groups in completed abortion rates between study arms was computed and non-inferiority was accepted if this interval lay completely on the left of the non-inferiority 5% margin, that is, if the difference falls within the predefined equivalence range of 5%. Homogeneity of the three study sites was assessed using the Higgins & Thompson index H. Stratified analysis for potential site effects was not conducted because the complete abortion rate at one site was 100% for both study groups.We conducted a sensitivity analysis to test two different outcome scenarios for women lost to follow-up. Based on observed success rates, we assumed a 100% success rate for women lost to follow-up in both scenarios in the physicians’ group. For the nurses’ group we assumed 78.6% and 71.4% success rates in the first and second scenario, respectively.Once a complete abortion was confirmed and women were given a contraceptive method or information, a study coordinator not linked to clinical care administered a satisfaction survey that the participants completed on-site. An acceptability scale was constructed using responses to the 14 questions. Some answers were binary – yes or no – and others were categorical – e.g. range of satisfaction and expectation levels. We scored the responses for each question using a range between 0 to 1, where the responses with the lowest acceptability received 0 points and responses with the highest acceptability received 1. The points generated for each question were summed to create a provider acceptability score per participant ranging from 0–14. The mean overall acceptability scores for each provider group were compared to determine women’s satisfaction.All analyses were conducted using SPSS version 18.0 (SPSS Inc., Chicago, USA). […]

Pipeline specifications

Software tools ConSole, SPSS
Applications Miscellaneous, Protein structure analysis
Organisms Homo sapiens
Chemicals Mifepristone, Misoprostol