Therapeutic Educational Intervention and Fibromyalgia: a Mixed Methods Research

Study design Mixed method research with a sequential exploratory design.

A three-stage procedure will be used:

1. Qualitative phase: collection and analysis of qualitative data.
2. Connection phase: based on the results obtained in the previous stage the content of the educational intervention will be developed.
3. Quantitative phase: the resulting educational intervention will be tested in a sample of the target population and subsequently the quantitative data will be collected and analyzed.

Qualitative Phase Objective To explore the evaluation (cognitive factors) and response (behavioral factors) associated with pain and poor sleep quality in Spanish women diagnosed with Fibromyalgia.

Methodological orientation and Theory Generic qualitative study Sampling, Sample Size, and Method of Approach In this phase, a non-probabilistic snowball sampling technique will be used. The inclusion of participants will stop when new ideas or data about the research topic stop appearing, that is, until the information is saturated.

Women who agree to participate in the qualitative phase will be contacted by the principal investigator to assess compliance with the established inclusion criteria and to read and sign the informed consent.

Data collection and analysis Qualitative data will be collected through in-depth semi-structured individual interviews.

The interviews will be conducted individually by the main researcher of the study in Spanish or Catalan, depending on the mother tongue of the interviewee. Also, the interview will be held in a place chosen by the participants to facilitate a comfortable environment.

All interviews will be recorded in digital format, transcribed and subsequently imported into the qualitative analysis software ATLAS.ti. A triangulation of researchers will be conducted.

Connection Phase The connection phase is of special importance in the development of projects with exploratory sequential mixed methodology since it is in this phase where the integration of the qualitative and quantitative phases is clear. In this project, the data of the qualitative phase are essential for the development of the content of the therapeutic educational intervention, whose effects will be evaluated in the quantitative phase by means of an RCT.

Once the qualitative data is analyzed the author will develop the content of the therapeutic educational intervention and the materials (videos, dossiers) that will be available on the website for the participants of the study.

Using the data of the qualitative phase for the development of the therapeutic educational intervention will assure that the materials are based on the FM patients' needs. The best and most current scientific evidence will be consulted so as to provide the participants with a high-quality website with proper information about pain and sleep in the context of FM. The latter is what makes this project an innovative approach in this field of research aimed to respond to the actual needs of FM patients' based on their own experience.

With the help of an information technology technician, the author will design, create and maintain the website. The website will be only accessible with a user number and password provided by the author to the participants once they are allocated to the treatment conditions.

Quantitative Phase Hypothesis A web-based therapeutic educational intervention on pain and poor sleep quality shows more significant clinical effects than the conventional medical treatment for the management of pain, poor sleep quality, catastrophizing of pain, beliefs and dysfunctional attitudes in relation to sleep and the state of health and quality of life associated with fibromyalgia in Spanish women diagnosed with fibromyalgia in a primary care setting.

Principal Objective To evaluate the effects of a web-based therapeutic educational intervention on pain intensity and sleep quality in Spanish women diagnosed with fibromyalgia compared to conventional treatment.

Secondary Objectives

To evaluate the effects of a web-based therapeutic educational intervention in Spanish women diagnosed with fibromyalgia compared to conventional treatment on:

• Pain Catastrophizing
• Dysfunctional beliefs and attitudes in relation to sleep
• Health status, functionality, and quality of life associated with FM Study Design A parallel, double-blind randomized controlled trial. Setting of the study Primary care centers in the city of Lleida Recruitment and sampling method Patients will be recruited from the Primary Care Centers of the city of Lleida. A list of women diagnosed with fibromyalgia will be requested to the board of the primary care of the city of Lleida.

A systematized sampling method will be used in order to assure that all the women in the list have the same chance for participating in the study. The principal investigator will call the women on the list and will meet whit those showing interest in participating so as to assess compliance with the inclusion criteria and to provide them with the information sheet and informed consent.

Intervention plan Experimental group: the subjects assigned to this group will follow a web-based therapeutic educational intervention about pain and poor sleep quality.

All the subjects assigned to this intervention will have free access to the website from any device with internet access and will be able to consult it as many times as they wish during the intervention.

Control group: the subjects assigned to this condition will continue with their usual treatment is based on the recommendations of the clinical practice guidelines for the treatment of FM "Guide of Fibromyalgia" developed by the Department of Health of the Generalitat de Catalunya and the Servei Català de Salut.

Outcomes Primary outcomes

• Pain intensity
• Sleep Quality
• Pain Catastrophizing
• Dysfunctional Beliefs and Attitudes about Sleep
• Health status and quality of life associated with fibromyalgia:

Sample Size According to the Granmo sample size calculation program, accepting an alpha risk of 0.05 and a beta risk of 0.2 in a bilateral contrast, 32 subjects are required in the first group and 32 in the second to detect a difference equal to or greater than 15 units. It is assumed that the common standard deviation is 12.63. A tracking loss rate of 20% has been estimated.

Randomization Type and Sequence Generation A simple randomization method will be used. A 1:1 ratio will be established for the allocation of participants in each group so that there is the same number of subjects in the experimental and in the control group. The randomization list will be generated through the STATS® computer program by a person specializing in statistics and not related to the study.

Allocation Concealment Mechanism and Implementation In order not to infer in a selection bias, the allocation must be hidden from the researchers responsible for the recruitment of patients. In the case of the present investigation, and given that the pertinent evaluations will be made through the website, there will be no researchers in charge of assessing the participants.

To ensure allocation concealment, a centralized randomization will be carried out through the internet. When the principal researcher ensures compliance with the inclusion criteria and the participant reads, accepts and signs the informed consent, the participants' number will be requested online. This number will not be in any way related to the intervention groups, so neither the researcher nor the participant can anticipate their assignment.

This same number will be entered on the website by the patient when she accesses the website and at that moment she will know the instructions to follow on the screen according to the group to which she has been assigned.

Blinding A double-blind study is proposed in which the participants and the study researchers will not know the group assigned to each subject. In fact, the evaluations will be carried out through the website.

Data Collection The variables to be studied will be evaluated through the questionnaires previously presented which must be completed by the participants of both intervention groups through the website at pre and post-intervention and at three and six months after the intervention.

In each of these five moments of data collection, the subjects of both treatment conditions will receive an email and WhatsApp as a reminder when the questionnaires are available in the website, if they still do not complete the questionnaires, they will be contacted by telephone.

The questionnaires of each patient will be automatically sent to a database to which only the statistician will have access. After each assessment moment, the data obtained will be exported to the "Statistical Package for Social Sciences Software" (SPSS).

Statistical Analysis For the univariate analysis, the variables will be described through measures of central tendency and position, such as the mean, the median, and the mode; dispersion measures such as interquartile range, standard deviation and variance. They will be represented by graphs and tables in order to facilitate the reading of the data.

Regarding the bivariate analysis, the Chi2 statistical coefficient of Pearson and the t-Student test will be used to determine whether or not there is a relationship between the dependent variables and the independent variables.

The statistical analysis to determine the statistical significance will be carried out assuming a confidence interval of 95% and an alpha value of 5% (0.05).

In relation to the clinical significance, the following values will be established:

• Pain intensity (VAS): it is established that a decrease of between 10 and 20% of pain intensity as the minimum clinically important difference, a change of ≥30% as a moderate clinical difference and, finally, a reduction in pain intensity ≥50% reflects substantial changes (32).
• Pain Catastrophizing (PCS): a reduction of the 15-30% is established as the minimum clinically significant change, changes between 30 and 50% are moderately clinically significant and reductions of ≥50% are indicative of substantial clinical improvement (37).
• Health status and Quality of Life related with FM (FIQ-R): a 45.5% change or a change of 27.04 points in the total score of the FIQ is established as the minimum clinically meaningful change (46).
• For the measurement tools whose minimal clinically important difference has not yet been determined, the Standard Median Deviation will be calculated.

ETHICAL ISSUES This study follows the basic ethical principles of respect for people, beneficence and justice established in the Belmont Report, the moral, ethical and legal principles of the Nuremberg Code, the principles of medical research that include human subjects of the Declaration of Helsinki and the "Guideline for Good Clinical Practice" (CPMP/ICH/135/95).

Also, given the management and use of personal data of the participants in both phases of the project and the use of a website for the development of the therapeutic educational intervention, this research will be subject to the "Reglamento (UE) 2016/679 del Parlamento Europeo y del Consejo de 27 de abril de 2016 relativo a la protección de las personas física en lo que respecta al tratamiento de datos personales y a la libre circulación de estos datos".

All participants will be provided with an informed consent document that will be accompanied by a full explanation regarding the investigation, the use of the data by the authors, as well as the laws that protect their rights.

As the intervention does not involve any physical activity/intervention, we expect not to have any physical side effect. However, patients will be advised to contact their family physician if they have any physical problem or any worsening of their condition.