Here is the design of a clinical trial:

Official Title: Open-Label Placebo Treatment of Women With Premenstrual Syndrome: A Randomized Controlled Trial

Included conditions:
- Premenstrual Syndrome

Study Armgroups:
- {'label': 'Treatment as Usual', 'type': 'NO_INTERVENTION', 'description': 'The treatment as usual (TAU) group will control for regression to the mean, spontaneous remission, natural course of disease, and the participants-provider interaction. Participants of the TAU group are allowed to continue their usual medication intake, given they are already on a stable dose (at least 30 days of intake) and the medication is not listed in the exclusion criteria.'}
- {'label': 'Integrative Open-Label Placebo', 'type': 'ACTIVE_COMPARATOR', 'description': 'The intervention will encompass an integrative administration of "P-Dragees rosa Lichtenstein", which are pink placebo dragées without any active ingredient. Each dragée contents the following substances: lactose monohydrate; magnesium stearate (Ph. Eur.); microcrystalline cellulose; highly dispersed silicon dioxide; white clay, macrogol glycerolhydroxy stearate (Ph. Eur.); Arabic gum; montanglycol wax; povidone (K 25); talcum; titanium dioxide (E 171); erythrosine; aluminium salt (E 127); calcium carbonate; sucrose; glucose syrup; maize starch; macrogol 6000.\n\nAll participants will be informed that the administered dragées are placebo dragées and participants will be instructed to take two dragées a day for six weeks. (Amendment regarding dosage since 08/18)', 'interventionNames': ['Other: P-Dragees rosa Lichtenstein']}
- {'label': 'Open-Label Placebo', 'type': 'ACTIVE_COMPARATOR', 'description': 'The intervention will encompass an administration of "P-Dragees rosa Lichtenstein", which are pink placebo dragées without any active ingredient. Each dragée contents the following substances: lactose monohydrate; magnesium stearate (Ph. Eur.); microcrystalline cellulose; highly dispersed silicon dioxide; white clay, macrogol glycerolhydroxy stearate (Ph. Eur.); Arabic gum; montanglycol wax; povidone (K 25); talcum; titanium dioxide (E 171); erythrosine; aluminium salt (E 127); calcium carbonate; sucrose; glucose syrup; maize starch; macrogol 6000.\n\nAll participants will be informed that the administered dragées are placebo dragées and participants will be instructed to take two dragées a day for six weeks. (Amendment regarding dosage since 08/18)', 'interventionNames': ['Other: P-Dragees rosa Lichtenstein']}

Interventions:
- {'type': 'OTHER', 'name': 'P-Dragees rosa Lichtenstein', 'description': 'Placebo dragées', 'armGroupLabels': ['Integrative Open-Label Placebo', 'Open-Label Placebo']}

Primary Outcomes:
- {'measure': 'PMS symptom intensity assessed by a PMS symptom diary sub sum score', 'description': 'Symptom intensity will be assessed by an intensity sub scale of the PMS symptom diary. Intensity will be rated by means of a six-level Likert scale, whereat 1 is the lowest rating of symptom intensity and 6 the highest.', 'timeFrame': 'Continuous measurement, starting from day 1 of the menstrual cycle (length of each cycle is on average 28 days) until the individual last day of the third menstrual cycle of each participant (assessment across three menstrual cycles in total)'}
- {'measure': 'PMS symptom interference assessed by a PMS symptom diary sub sum score', 'description': 'Symptom interference will be assessed by an interference sub scale of the PMS symptom diary. Interference will be rated by means of a six-level Likert scale, whereat 1 is the lowest rating of interference and 6 the highest.', 'timeFrame': 'Continuous measurement, starting from day 1 of the menstrual cycle (length of each cycle is on average 28 days) until the individual last day of the third menstrual cycle of each participant (assessment across three menstrual cycles in total)'}

Please estimate the sample size based on the assumption: 
Significance level (alpha) is set at 0.05. Power is considered at 0.8 and 0.9. A multilevel approach is adopted for more precise estimations. Correlation among different time points is assumed to be 0.5.
Sample size and statistical analysis of data
      
        Data management
        For data management, Microsoft Excel and LabKey, which is hosted by the University of Basel, is used. Study data are collected at the web server-based software LimeSurvey. Only authorised study team members are able to view and export data. Entries and actions are marked with the initials of the respective study member.
      
      
        Sample size
        A calculation with a power analysis on the basis of an F-test and an analysis of covariance for three groups, using the statistical software G*Power, indicated a total sample size of 206 participants needed for a power of 0.9 and a total sample size of 158 participants for a power of 0.8 to detect a medium effect size of f=0.25 (equals d=0.5) with an alpha-level of 0.05.
        Since we will adopt a multilevel approach which enables more precise estimations, we also conducted a power analysis on a repeated-measures analysis of variance, using G*Power, whereby we are interested in the interaction between time (menstrual cycles, 3 levels) and study groups (3 levels). If the correlation for the outcome among the different time points (1â3 cycles) is assumed to be 0.5, then based on an alpha-level of 0.05, a power of 0.8 and a medium effect size of f=0.25, the required samples size is 36 (12 per group). Accordingly, for the main effect of menstrual cycle, we would need 30 participants (10 per group), and for the main effect of study group we would need 108 participants (36 per group). On this basis, we chose a conservative total sample size of 150 participants (50 per group). It is worth noting that most OLP studies reported effect sizes that are generally higher than d=0.5 (eg, chronic low back pain: d=0.771; irritable bowel syndrome: d=0.79).2 However, in another OLP study for patients suffering from major depressive disorder,5 the authors reported an effect size of d=0.54 while stating that the study was limited by low statistical power (ie, the findings did not support the hypothesis that OLPs are effective in depression). Since PMS is not only characterised by physical complaints, yet also by psychological symptoms such as depressive mood, and since there is no specific research on OLP effects and effect sizes in PMS, we considered a conservative medium effect size as more appropriate. This resulted in a more conservative sample size.
      
      
        Statistical analysis
        For the testing of the primary hypotheses, the daily data from three menstrual cycles of a symptom diary is examined. Because of the hierarchical structure of the data (menstrual cycles as level-1 are nested within participants as level-2) and given our aim to predict post-interventional changes between menstrual cycles as the primary outcome, a multilevel modelling approach will be adopted. Multilevel models take care of the interdependence of the hierarchical data that arises due to the fact that observations within the same individual are typically more similar to each other compared to observations between individuals.30 31 Here, we will analyse temporal changes across menstrual cycles of symptom intensity and interference among the different study groups. To compare a TAU group with two intervention groups and to evaluate the effect of the applied treatment rationale, the following linear a priori contrast will be tested for the factor study group: TAU<OLPâ<OLP+. Thus, based on published findings,6 we expect that the effect of OLPâ lies between that of TAU and OLP+. Out statistical model contains menstrual cycle as within-subject factor with three levels (C1, C2 and C3), study group as between-subject factor with three levels (TAU, OLP+ and OLPâ), and the interaction between the two factors. In line with recommendations by Fitzmaurice et al,32 we will treat baseline values (ie, values at C1) as a part of the outcome vector and assume that the means among study groups are equal at baseline since participants are randomised. The model contains the two main effects study group contrast (defined above) and menstrual cycle (temporal effect) plus the interaction between the two. We will be primarily interested in the interaction term as it tests for the differential temporal change between study groups in order as defined in the linear contrast.
        Analyses of secondary outcomes are based on the same multilevel model as used for primary outcomes, but will be considered exploratively, thereby not correcting for multiple tests.33

      
      
        Monitoring
        The study is monitored for quality and regulatory adherence. The monitor, who is not involved in our study and approved by the local ethical committee, verifies the qualification of the investigators and study team members, and monitors sound and appropriate documentation.
      
      
        Ethics and dissemination
        The present protocol and applied informed consent forms were approved with regard to their content and compliance with ethical regulations by the Ethics Committee Northwest and Central Switzerland. The study is carried out with principles enunciated in the current version of the Declaration of Helsinki34 and the guidelines of Good Clinical Practice issued by the International Conference on Harmonization.35

        Women interested in study participation receive a participant information sheet and consent form, describing the study and providing sufficient information for an informed decision about participation and data confidentiality and detailed oral information is provided. The results of the planned analyses will be published in a peer-reviewed journal.