Knowledge Gaps in Reproductive Health among Women with MS (KNOWwMS): a project protocol

Knowledge Gaps in Reproductive Health among Women with MS (KNOWwMS): a project protocol Authors Claudia De Santisa, Riley Boveb, Dina Jacobsc, Jennifer McDonelld, Nick Rijkee, Deanna Saylorf, Shanthi Viswanathang, Francesco Noninoa, Elisa Baldina Authors affiliations a. IRCCS, Istituto delle Scienze Neurologiche di Bologna, Epidemiology and Statistics Unit, Cochrane Review Group Multiple Sclerosis and Rare Diseases of the CNS, Bologna, Italy Email: [email protected]; [email protected]; [email protected] b. University of California, San Francisco (UCSF), Weill Institute for Neurosciences, US Email: [email protected] c. Perelman School of Medicine at the University of Pennsylvania, Department of Neurology, US Email: [email protected] d. MS Canada, Toronto, ON, Canada Email: [email protected] e. Multiple Sclerosis International Federation, London, UK Email: [email protected] f. University of North Carolina School of Medicine, US; University Teaching Hospital, Lusaka, Zambia Email: [email protected] g. Kuala Lumpur Hospital, Department of Neurology, Malaysia Email: [email protected] Corresponding author Claudia De Santis IRCCS, Istituto delle Scienze Neurologiche di Bologna, Epidemiology and Statistics Unit, Cochrane Review Group Multiple Sclerosis and Rare Diseases of the CNS, Bologna, Italy Via Altura 3, 40139 Bologna, Italy Phone: +39 3387972690 E-mail: [email protected] Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Abstract Background: Multiple sclerosis (MS) is a chronic condition affecting primarily women in childbearing age. Studies have highlighted the significant challenges and limitations women face in accessing reliable and consistent information on reproductive health from neurologists and other healthcare professionals, especially in limited resources settings. In these global settings, there is a need to explore the core set of information about MS and its impact on their reproductive health that could lead to better awareness and self-reliance. Aim: The project aims to define a set of information that any woman with MS should know (“Core Knowledge Set”), tailored towards resource-limited settings. This set will be aimed at filling key knowledge gaps reported by women with MS regarding the connection between MS and reproductive health. Additionally, it may serve as a valuable tool to support the adoption of evidence-based recommendations for improving access to MS-related information. Methods: A mixed methodology has been developed for informing the set through two stages: (a) mapping the available evidence by means of a systematic scoping review of the published literature addressing information needs among women with MS, and (b) two international, anonymous on-line surveys aimed at assessing access to information sources and knowledge gaps from the perspective of women as well as MS healthcare professionals, focusing on limited resources settings. Keywords Multiple sclerosis; Knowledge gap; Reproductive health; Women health 1. Background Multiple sclerosis (MS) is a chronic autoimmune condition affecting approximately 3 million people worldwide, with an increasing prevalence observed across most regions globally (Walton et al., 2020). Women are disproportionately affected by MS compared to men, with a ratio of 2-3 to 1. MS is commonly diagnosed between the ages of 20 and 50, which are the prime reproductive years for women (Bove & Chitnis, 2014). Evidence suggests that pregnancy does not adversely affect the longterm course of MS and may even have a beneficial effect in MS, with overall better MS outcomes in women who have been pregnant (Keyhanian et al., 2012; Lamaita et al., 2021). Moreover, MS does not seem to affect pregnancy outcomes (MacDonald et al., 2019), while many disease-modifying therapies (DMTs) commonly used in MS care are contraindicated during pregnancy and breastfeeding (Bove & Chitnis, 2014). Given the higher prevalence of MS among women and the typical age of diagnosis, ensuring the availability of clear, comprehensible, and easily accessible information about reproductive health is a pressing public health priority. However, numerous studies have highlighted the significant challenges and limitations women with MS (WwMS) face in accessing reliable and consistent information from neurologists and other healthcare professionals (Ghafoori et al., 2020; KosmalaAnderson & Wallace, 2013). Although research on women's reproductive health in MS is increasing, most studies are conducted in high-income countries, particularly in Europe and North America, while data from lowand middle-income regions are scarce (Ross et al., 2022). Therefore, WwMS face unique challenges in managing their reproductive health while also coping with the burden of a chronic, disabling disease. Providing WwMS with a core set of information about their condition and its impact on pregnancy and breastfeeding could be a valuable step towards a better awareness and self-reliance, particularly in settings where limited resources hamper access to appropriate information. The project Knowledge Gaps in Reproductive Health among Women with MS (KNOWwMS) aims to globally address such issue by defining a set of information that any woman with MS should know (“Core Knowledge Set”). The set will be aimed at filling knowledge gaps reported by WwMS about the impact of MS on reproductive health and may be a useful a tool to facilitate the uptake of evidence-based recommendations addressing access to information on MS in restricted resource settings. 2. Methods The development of each stage of the KNOWwMS project will be overseen by an international, multistakeholder Scientific Advisory Group (SAG) (Appendix A). In order to ensure methodological consistency, a Coordinating Team (CT) (Appendix A) will facilitate communication and provide timely information to the researchers involved in the project, schedule regular meetings of the SAG, and ensure consistency between the protocol and the development of the project. KNOWwMS is a mixed-method project developed in two main stages: (a) mapping the available evidence by means of a systematic scoping review of the published literature addressing information needs among WwMS, and (b) two international, anonymous on-line surveys aimed at assessing access to information sources and knowledge gaps from the perspective of WwMS as well as MS healthcare professionals. 2.1 Systematic scoping review The main aim of the scoping review is to comprehensively map out the existing literature regarding knowledge gaps and information needs among WwMS during childbearing age, in order to better understand the current landscape and to identify areas where further research may be warranted. Additionally, the review will investigate the role of neurologists and other healthcare professionals in providing counselling and guidance on family planning within the context of MS care. The review’s findings may help improve support strategies for women with MS as they navigate reproductive health decisions, while also providing insight into current practices among MS professionals in guiding their patients. Studies with any design evaluating knowledge gaps and information needs about reproductive health by WwMS will be included. Namely, the following key reproductive health indicators will be considered: • Reproductive health knowledge; • Impact of MS diagnosis on family planning and breastfeeding decisions; • Communication and counselling received from healthcare providers regarding reproductive health; • Access to contraception; • Rate of planned vs. unplanned pregnancies; • Access to general prenatal care; • Completed family size for women currently aged 50-55 years; • Age at first childbirth. Among studies evaluating the role of MS healthcare providers, including – but not limited to – neurologists in childbearing planning and guidance for WwMS, we will select those providing information about the following issues: • Characteristics of the guidance provided to WwMS regarding family planning counselling; • Knowledge gaps regarding reproductive health management for WwMS; • Perceived self-efficacy about providing family planning counselling; • Knowledge and use of clinical recommendations; • Adherence to regulatory labels (by FDA, EMA, and other regulatory agencies). The systematic scoping review will be conducted according to the JBI Manual for Evidence Synthesis methodology (Peters et al., 2020) and the reporting will follow the reporting guideline PRISMA-ScR (Tricco et al., 2018). The methods and results of the scoping review will be reported and submitted to a peer reviewed medical journal. The protocol of the review has been registered on the Zenodo repository (protocol registration number: 10.5281/zenodo.13866567). 2.2 International survey for WwMS The survey among WwMS aims to gather data on access to information, knowledge gaps, and misinformation concerning reproductive health in WwMS. The main questions of the survey will be informed by the findings of the scoping review and refined by the SAG. All questions will have predefined answers, and a final open-ended question will allow a free text addition by the respondents on topics not covered by the questionnaire. The target responders of the survey will be women with a diagnosis of MS aged 18 years or older living in different geographic areas, encompassing highas well as lowand middle-income countries, but with a preferential focus on the latter. Participation to the survey will be fostered by dissemination through contacting local MS advocacy groups, medical societies such as the TRIMS network, and Cochrane Geographic Groups. WwMS will also be individually reached by their treating physicians or other healthcare professionals involved in MS care. The electronic form will be available online for six-months. To facilitate effective global participation in non-English-speaking countries, the survey will also be available in languages other than English, that will be defined based on participating countries. Questionnaire translations from English to other languages will be performed by native-speaking volunteers and back-translated for validity assurance. Respondents unable to independently fill out the online survey (e.g., because of cultural, technological or language barriers), will be assisted by a treating physician or another healthcare professional involved in MS care, referred as "Country Champion" (CC) hereafter. Depending on local needs, CC may support WwMS as follows: • Providing a tablet or other electronic device available at the facility to ease the completion of the online survey, ensuring that the platform is fully functional and accessible for WwMS. The participant will therefore complete the survey independently during their visit. • Orally administering the survey to the participant and digitally reporting their answers on the online survey platform. Country champions will be responsible to submit the study protocol to their local Institutional Review Board (IRB), if required, and receiving its approval before proceeding with the survey administration. Data will be collected anonymously by means of an electronic form stored on the Cochrane Drupal platform (a free and open-source web content management framework), located in the UK and compliant with UK and European General Data Protection Regulation (GDPR). Adherence to procedures and timelines, as well adequate information to the CCs as needed will be provided by the CT. 2.3 International survey for MS Healthcare Professionals The survey, informed by the scoping review and refined by the SAG, will target healthcare professionals engaged in the treatment and management of WwMS. Its purpose is to complement the findings of the survey for WwMS, by exploring healthcare professionals' perspectives on knowledge gaps, information needs, and concerns raised by WwMS during their clinical practice. Additionally, the survey aims to gather valuable data on MS professionals' views regarding reproductive health counselling, interdisciplinary collaboration, and the sources of information available in their local setting. This survey as well will be available online as an anonymous electronic form on the Cochrane Drupal platform in English language only, over a six-month period. The survey will be disseminated by the Country Champions to their colleagues, local professional boards and networks. At the end of the data collection of both surveys, the CT will ensure data quality and perform a descriptive analysis of the anonymous, aggregated responses, that will be assessed and interpreted by the SAG. Descriptive analysis will be conducted using weighted natural frequencies of responses incorporating both individual and setting-specific variables. Open-ended responses will be analysed thematically. Translations of potential non-English responses will be carried out by CCs. 2.4 Core Knowledge Set The Core Knowledge Set will be developed based on the survey results and structured around three main themes: family planning, pregnancy, and breastfeeding. Access to counselling and information sources will also be assessed. The content will be organised in plain language statements and figures sketched by a professional illustrator. The set will be developed as informational material in electronic format to be disseminated through digital platforms (social media and websites) as well as physical resources (pamphlets and information boards) to be disseminated in healthcare facilities. Setting-specific dissemination strategies will be suggested by local CCs. Reproductive health of WwMS, especially those in limited-resource settings, may be improved through access to accurate, easily understandable information supporting informed decisions. Alignment and discrepancies between the perspective of healthcare professionals and of WwMS on access to information and counselling will be assessed by comparing responses in both questionnaires. Findings on potential inconsistencies between the two perspectives may inform quality improvement processes by health decision-makers aimed at improving access to information on reproductive health by WwMS and by MS health professionals.