title: How to assess success of treatment when using multiple doses: the case of misoprostol for medical abortion.
abstract: BACKGROUND
  The assessment of treatment success in clinical trials when multiple (repeated) doses (courses) are involved is quite common, for example, in the case of infertility treatment with assisted reproductive technology (ART), and medical abortion using misoprostol alone or in combination with mifepristone. Under these or similar circumstances, most researchers assess success using binomial proportions after a certain number of consecutive doses, and some have used survival analysis. In this paper we discuss the main problems in using binomial proportions to summarize (the overall) efficacy after two or more consecutive doses of the relevant treatment, particularly for the case of misoprostol in medical abortion studies. We later discuss why the survival analysis is best suited under these circumstances, and illustrate this by using simulated data.
  
  
  METHODS
  The formulas required for the binomial proportion and survival analysis (without and with competing risks) approaches are summarized and analytically compared. Additionally, numerical results are computed and compared between the two approaches, for several theoretical scenarios.
  
  
  RESULTS
  The main conceptual limitations of the binomial proportion approach are identified and discussed, caused mainly by the presence of censoring and competing risks, and it is demonstrated how survival analysis can solve these problems. In general, the binomial proportion approach tends to underestimate the "real" success rate, and tends to overestimate the corresponding standard error.
  
  
  CONCLUSIONS
  Depending on the rates of censored observations or competing events between repeated doses of the treatment, the bias of the binomial proportion approach as compared to the survival analysis approaches varies; however, the use of the binomial approach is unjustified as the survival analysis options are well known and available in multiple statistical packages. Our conclusions also apply to other situations where success is estimated after multiple (repeated) doses (courses) of the treatment.
authors.affiliation: Department of Reproductive Health and Research, World Health Organization, 1211, Geneva 27, Switzerland. seuca@who.int.
authors.forename: Armando H
authors.initials: AH
authors.lastname: Seuc
authors.affiliation: Department of Global Health and Population, Harvard T. H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. ishah@hsph.harvard.edu.
authors.forename: Iqbal H
authors.initials: IH
authors.lastname: Shah
authors.affiliation: Department of Reproductive Health and Research, World Health Organization, 1211, Geneva 27, Switzerland. alimoa@who.int.
authors.forename: Moazzam
authors.initials: M
authors.lastname: Ali
authors.affiliation: Population Council Mexico, Insurgentes Sur 2453 - Torre Murano Piso 9 Local 903, Col. Tizapán, Del. Álvaro Obregón, México City, 01090, Mexico. cdiaz@popcouncil.org.
authors.forename: Claudia
authors.initials: C
authors.lastname: Diaz-Olavarrieta
authors.affiliation: Department of Reproductive Health and Research, World Health Organization, 1211, Geneva 27, Switzerland. temmermanm@who.int.
authors.forename: Marleen
authors.initials: M
authors.lastname: Temmerman
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000008:administration & dosage* / Q000009:adverse effects; D000028:Abortion, Induced / Q000379:methods / Q000706:statistics & numerical data*; D002986:Clinical Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015993:Life Tables; D016595:Misoprostol / Q000008:administration & dosage* / Q000009:adverse effects; D015233:Models, Statistical; D009716:Numerical Analysis, Computer-Assisted; D011247:Pregnancy; D012107:Research Design / Q000706:statistics & numerical data*; D016896:Treatment Outcome
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D016595:Misoprostol