Data management

Data to be managed include qualitative data (i.e., focus groups and interviews), survey data, logistic data, personal data and diary data. Focus group data will be anonymized, with only general information on participants’ roles, professions, or diagnoses reported. Individual focus group contributions will not be linked to demographic or survey data. Screening information, interviews and quantitative survey responses, however, will be linked using a unique participant identifier stored in a secure key file. Throughout the study, audio files and transcripts of qualitative data, as well as personal data, will be stored separately on the secured UMCG drive. Surveys will be administered via RoQua [38], a secure web application for outcome monitoring in health care and research. Logistic data will be captured in REDCap (Research Electronic Data Capture) [39], a secure platform for managing research databases. REDCap data are automatically backed up daily on the internal servers. Logistic data include all information related to the execution of research activities, captured through digital checklists at each procedural step. Upon study closure, REDCap will be frozen following verification and resolution of all queries. All raw data files, as well as qualitative and personal data, will be stored in password-protected folders, locked for editing, and labeled with the save date.

The final menstrual cycle diary will be embedded within an Experience Sampling Method (ESM)-based tool named PErsonalized Treatment by Real-time Assessment (PETRA), which was previously developed to support treatment of patients in mental health care [40]. ESM is a scientific method commonly used for self-monitoring in mental health care [41]. PETRA is a scientific, web-based platform that is integrated into the Electronic Health Record system in RoQua across eight major Dutch mental health care institutions and is also accessible to other UMCG departments, including gynecology. Diary data are therefore stored directly in a patient’s Electronic Health Record. In the PETRA platform, informed consent for the use of diary data in research is embedded in the user interface and legally secured through the PETRA consortium agreement, enabling future ESM studies. PETRA was co-designed with psychiatric clinicians and patients [40], and is available in Dutch and English [42]. It is a flexible tool used in routine mental health care to support various goals, such as monitoring treatment progress and helping clinicians better understand patients’ momentary experiences to inform diagnosis and personalized treatment. In short: PETRA consists of four key components: 1) a goal-setting decision aid, 2) a repository of diary items, 3) an SMS-based diary delivery system, and 4) a feedback module. In line with patient and clinician preferences, PETRA allows personalization of the digital diary content, schedule, and duration of monitoring. Its ESM-based feedback module includes descriptive graphs and summary statistics and aims to support data-driven discussions and shared decision-making during diagnostic assessments and treatment.

CycleWise study design

The menstrual cycle diary development follows a human-centered, iterative design approach guided by the CeHRes roadmap and employs a multimethod strategy [37]. Because this study is not a clinical trial, trial registration is not applicable.

Study procedures per CeHRes roadmap phase

Below, we first outline how each phase of the CeHRes roadmap is implemented in this study, along with the specific setting and procedures for each of the five phases before moving to participant criteria. Fig 1 presents an overview of the research activities associated with each phase.

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Fig 1. Overview of the CeHRes Roadmap phases and their application in this study.

The upper layer outlines the CeHRes roadmap phases, while the lower layer illustrates how these phases are applied in the CycleWise study.

https://doi.org/10.1371/journal.pone.0342586.g001

Participants

For participation in the CeHRes roadmap–defined value specification phase, patients must be 18 years or older and have a past, current, or suspected PMD diagnosis. Eligibility will be assessed during the screening interview (Table A in S1 File; questions 1, 2, or 12). Clinicians will be eligible if they provide care for patients diagnosed with a PMD, including professionals from routine gynecology or psychiatric care services. Exclusion criteria for both patients and clinicians include insufficient proficiency in Dutch.

In the evaluation phase, eligible patients will also be 18 years or older and have a past, current or suspected PMD diagnosis. Additionally, these patients must be referred for psychiatric or gynecological treatment at the UMCG or another mental health care institution with access to PETRA. Additional criteria include having a regular menstrual cycle with a cycle length between 21–35 days and the ability to provide informed consent. Exclusion criteria are acute medical conditions hindering participation, insufficient proficiency in Dutch, or unwillingness or inability to use a smartphone. Clinician eligibility criteria will be identical to those in the value specification phase.

Sample size

In the value specification phase, two focus groups (each n = 3 patients and n = 3 clinicians) will be conducted to identify user needs. The second group will help verify and refine the needs identified in the first. A member check, involving the same patients and clinicians from the previous groups, will be conducted to evaluate the prototype in the design phase. The sample size is based on prior research indicating that two to three focus groups with six to eight participants typically cover at least 80% of thematic content [48].

In the evaluation phase, the primary assessment method is the semi‑structured interview. Sample size will be guided by the principle of data saturation; we anticipate reaching thematic saturation with approximately 10 patient and 10 clinician interviews [49], but additional participants will be recruited if new themes continue to emerge. The quantitative evaluation survey will be distributed to approximately 20 patients and 20 clinicians to descriptively assess user experiences and to triangulate and complement the qualitative findings.

Material

All interview and focus group guides, along with the survey for participants who never used the menstrual cycle diary, are provided in the supporting information. These materials were iteratively reviewed by the project group to reach consensus on content and items. To describe the sample of the evaluation phase, patients will answer a one-time assessment, consisting of the PSST, OQ-45 and SCL-90-r.

The Dutch version of the PSST will be used to retrospectively assess PMS and PMDD diagnoses [43]. The PSST consists of two main sections with a total of 19 items (±5 minutes). The first section evaluates physical and psychological symptoms (14 items), while the second section (5 items), assesses the impact of these symptoms on the patients’ daily life. Each item is rated on a 4-point Likert scale, ranging from ‘not at all’ (0) to ‘severe’ (3). According to the PSST, PMDD is diagnosed when at least one core emotional symptom is severe, four or more additional symptoms are moderate to severe, and at least one domain of functioning is severely impaired. Moderate to severe PMS is diagnosed when at least one core emotional symptom and four or more additional symptoms are moderate to severe, with at least one moderate to severe functional impairment. Cronbach’s alphas for the first and second sections have previously been reported as 0.96 and 0.91, respectively [50], indicating excellent internal consistency.

The Dutch version of the OQ-45 will evaluate psychological functioning [44]. The OQ consists of 45 items (±10 minutes) that are scored on a 5-point Likert scale, ranging from ‘never’ (1) to ‘almost always’ (5). Three subscales measure psychological functioning in different domains: symptom distress (25 items), interpersonal relations (11 items) and social role performance (9 items). Cronbach’s alphas for the subscales and total score have previously been reported as 0.91, 0.80, 0.69 and 0.93, respectively in clinical samples [51], indicating acceptable to excellent internal consistency.

The Dutch version of the SCL-90-r will assess the severity of physical and psychiatric symptoms (45). The SCL-90-r contains 90 items (±20 minutes), each scored on a 5-point Likert scale ranging from ‘not at all’ (0) to ‘very much’ (4). Items are distributed across eight symptom dimensions (somatization; 12 items, obsessive–compulsive; 10 items, interpersonal sensitivity; 9 items, depression; 13 items, anxiety; 10 items, hostility; 6 items, phobic anxiety; 7 items, paranoid ideation; 6 items, psychoticism; 10 items) and three global indices (Global Severity Index, Positive Symptom Distress Index, Positive Symptom Total). Cronbach’s alphas have previously been reported to range between 0.69 and 0.87 for the subscales [52], indicating acceptable to good internal consistency.

As part of the end-of-study evaluation survey, we will assess patient engagement using the TWEETS [46] and professional engagement using the PEEHTS [47]. Both 9-item scales evaluate behavioral, cognitive, and affective engagement (±5 minutes), with responses scored on a 5-point Likert scale ranging from ‘strongly disagree’ (1) to ‘strongly agree (5).’ Cronbach’s alpha has been reported as 0.86 for the TWEETS [46] and 0.89 for the PEEHTS [47], indicating good internal consistency.

Analytical approach

Qualitative data will be analyzed using the Qualitative Analysis Guide of Leuven (QUAGOL), a systematic framework for qualitative research [53]. Following QUAGOL, two researchers will first familiarize themselves with the focus group and interview transcripts through repeated readings and the creation of narrative summaries, which will then guide subsequent inductive coding and thematic analysis using ATLAS.ti software (version 23).

For both focus groups and interviews, two independent raters will code the transcripts and reconcile differences through consensus discussions [53]. For the interviews, an initial code list will be developed based on the first two transcripts and iteratively refined as new data emerge. Resulting codes from both data sources will be organized into clusters to inform the development of broader themes, which will be reviewed and validated in team meetings to ensure consistent interpretation. Quantitative data from the evaluation survey will be analyzed using descriptive statistics.

Strengths and limitations

This study has several notable strengths. First, it helps filling a critical gap by developing a digital tool to support the diagnosis and personalized treatment of premenstrual disorders, which are often under-recognized in mental health care and research [24,25]. Multidisciplinary collaboration ensures the diary’s relevance across specialties involved in the routine care of patients with premenstrual disorders. Engaging stakeholders throughout all phases of tool development increases the likelihood of successful adoption and sustained use in clinical practice [37]. The multi-phase, iterative study design allows for continuous refinement based on end-user feedback, while integration into existing workflows supports seamless implementation. Testing in routine clinical settings with both patients and clinicians ensures real-world applicability. The mixed-method approach provides a comprehensive evaluation of usability and impact.

However, the study is not devoid of limitations. This study focuses on short-term (i.e., two menstrual cycles) usability and acceptability, without follow-up on long-term adoption or clinical outcomes. Selection bias may also be a concern, as patients who choose to participate in focus groups may be more motivated or comfortable discussing menstrual health, while others may be deterred by ongoing stigma surrounding the menstrual cycle [56], potentially limiting the diversity of perspectives captured. Moreover, the generalizability of the findings is limited. PETRA is currently available in only eight Dutch mental health care institutions and for research purposes on demand, which may restrict the diversity of clinical settings where the digital menstrual cycle diary can be implemented. However, PETRA is technically ready and adaptable for broader implementation. The PETRA team is open to collaborations in both (mental) health care and research settings, supporting future expansion and evaluation across more diverse contexts.

Despite these limitations, this study represents an important step toward addressing the unmet need for a flexible digital menstrual cycle diary to support personalized symptom tracking in patients diagnosed with premenstrual disorders. By enabling the assessment of menstrual cycle–related symptom fluctuations in real-life contexts, this approach paves the way for future studies to develop interventions aimed at managing premenstrual symptoms and ultimately improving care for patients with premenstrual disorders.