Towards Sex- and Gender-Sensitive Pain Management: Participatory Development of the GESCO Intervention for Chronic Non-Cancer Pain and Long-Term Opioid Therapy in Primary Care

Background

Chronic non-cancer pain (CNCP) is a globally prevalent condition, with opioids commonly employed as part of its management. As opioid-related morbidity and mortality continue to rise globally, public health efforts are increasingly focused on a critical evaluation of how these medications are prescribed.^1–3 Evidence shows that only a small proportion of patients benefits from long-term opioid therapy (LTOT). Other treatment options, such as non-drug therapies, are equally effective at reducing pain.^4–8 This aligns with the biopsychosocial model, which posits that illness is not merely a biological symptom but a complex interplay of physiological, psychological, and social factors.⁹ To prevent patients from reaching a therapeutic impasse in which the effect of opioids is no longer in proportion to the side effects, adverse drug events or the risk of addiction, it is essential that doctors and patients have a strong, trusting relationship.^7,10,11 In this context, research suggests that sex and gender of both the patient and the doctor are crucial factors influencing the complex pathogenesis and disease progression.

As a project team, we are guided by the following scientific definitions of sex and gender: The term “sex” is typically operationalized by biological markers, including the presence of primary and secondary sex organs, chromosomal composition, and hormone concentrations.¹² While sex has traditionally been categorized within a binary system (female/male), these biological markers often exist on a continuum, as evidenced by intersex variations and the natural diversity in hormonal and genetic expressions. Consequently, sex is increasingly understood as a multi-dimensional biological spectrum rather than a strict binary.¹³

We distinguish sex from “gender”, which is a term used to describe socially constructed roles, identities and relationships. There is a spectrum of gender identities that individuals may identify with and express themselves through.¹³ It influences the way people perceive themselves, how they interact, and the distribution of power and resources in society.¹³ Gender is a multidimensional and complex concept that is shaped by social norms and values.¹⁴ Furthermore, gender interacts with other socio-cultural categories, such as socio-economic position.¹²

The term “sex and gender-sensitive intervention” refers to the consideration of biological and social aspects in the therapeutic process. Our work is conducted in accordance with the Sex and Gender Equity in Research guidelines (SAGE)¹³ and the guiding questions on embedding sex and gender into pain research, as published by Keogh and Boerner.¹⁵

The impact of sex and gender on chronic pain encompasses biological, psychological, and social dimensions.^15–17 At the biological level, hormonal influences, immune system function, and neurochemical processes contribute to sex-specific differences in pain perception and processing.^16,18,19 These biological distinctions also modulate the pharmacodynamics of analgesic agents, particularly opioids.¹⁸ Moreover, gender significantly influences the prevalence of chronic pain and its associated comorbidities, interacting in complex ways with psychosocial factors.¹⁹ Internalized gender roles have been shown to affect pain tolerance,²⁰ and men and women tend to adopt distinct coping strategies in response to pain.²¹ Also, gender may influence the quality of the doctor-patient relationship and impacts the treatment experience.^13,22,23 Communication dynamics within medical consultations are shaped by the gender of both the doctor and the patient.²¹ Furthermore, treatment preferences differ by gender; women, in particular, appear to derive greater benefit from multimodal therapeutic approaches and group-based interventions.²⁴ However, these factors do not act in isolation but are embedded in an intersectional framework. Beyond sex and gender roles, factors such as age, socioeconomic status, and cultural background intersect to shape individual pain experiences and healthcare access.^13,15 General practitioners (GPs) play a central role in CNCP management: they are often the first to initiate opioid therapy and remain responsible for its continuation and monitoring.²⁵ Accordingly, the focus of this study is the general practice setting, specifically as a primary site where sex and gender (intertwined with further intersectional factors) manifest and influence clinical decision-making.

In the German primary care system, however, this responsibility is characterized by significant structural challenges. Brief consultation windows and a reimbursement model that often favors somatic interventions over time-intensive psychosocial counseling can hinder the implementation of a conversational intervention.

There are various intervention studies focused on optimizing opioid management; however, there is still no satisfactory evidence for their effectiveness.^26,27 Despite the established relevance of gender-specific factors and relational work in pain therapy, there is a notable lack of interventions that systematically integrate these dimensions.¹⁶ Rather than evaluating the efficacy of opioids themselves, our project aims to close this gap by developing and evaluating a management approach that accounts for the complex interplay of gender, communication, and the GP-patient relationship to improve the quality and safety of CNCP care. The present study forms part of a larger feasibility project (GESCO – Gender-sensitive care for chronic non-cancer pain patients receiving long-term opioid therapy)²⁸ to elicit, pilot, evaluate and refine a sex- and gender-sensitive primary care intervention for patients with CNCP receiving LTOT guided by the Guidance for conducting feasibility and pilot studies for implementation trials by Pearson et al²⁹ and the updated MRC Framework.³⁰ The study obtained ethical approval from the Ethics Commission of Witten/Herdecke University (reference number: 138/2022, date of approval: 08/25/2022, amendment: 08/29/2023) and is funded by the German Federal Ministry of Health (funding numbers 2522FSB14A/ 2522FSB14B).

The GESCO study is conducted in two phases.²⁸ Phase 1 focuses on creating a database and developing the intervention in collaboration with stakeholders. Phase 2 will test the intervention in ten general practices with 50 patients with CNCP receiving LTOT, using an effectiveness–implementation hybrid design.²⁹ This includes a single-arm, pre-post comparison to assess preliminary effects and feasibility, accompanied by a process evaluation.²⁹ The findings will inform the refinement of the intervention for future application.

The present article reports on Phase 1: the creation of a database and the participatory development of the multifaceted GESCO intervention, incorporating a Theory of Change (ToC)^31,32 drawing on behavior change theory.³³

Methods

This paper outlines the process of developing of the complex GESCO intervention for implementation in general practice. In Germany, general practice is a medical specialty requiring board certification. GPs are the primary initiators and coordinators of opioid therapy,²⁵ making them the most appropriate target group for the planned intervention. A detailed overview of the overall study design is provided in the study protocol.²⁸ Briefly, the GESCO study comprises two phases (1. Intervention development; 2. Pilot testing and refinement), with Phase 1 reported in the present publication. The development process was guided by the updated UK Medical Research Council (MRC) Framework for developing and evaluating complex interventions.³⁰ Based on this, we defined a set of core principles that informed conceptual and methodological decisions³⁴ (see Table 1).

Table 1 Guiding Principles of the Intervention Development

Stakeholder Engagement

The GESCO study group consists of a project team and an advisory board. The project team comprises eight female and four male researchers from the fields of social science (n=1), psychology (n=1), public health (n=2), pharmacology (n=2), biostatistics (n=1), and medicine (n=5). A multi-perspective advisory board supports this team and contributes to the conceptual development, implementation, and evaluation/reflection throughout all project phases. The advisory board includes one female and one male patient representative, both living with CNCP and with personal experience of LTOT, as well as experts in general practice (n=2), pain medicine (n=1), addiction medicine (n=2), psychology (n=1), health care education (n=1), sociology (n=1), gender-related pharmacology (n=1), and participatory research (n=1). The team regularly updates the advisory board on study progress and obtains its feedback during quarterly meetings.

The Institute of General Practice and Primary Care (iamag) at Witten/Herdecke University maintains a patient advisory board, which contributed to the GESCO study by providing patient-centered perspectives.³⁵ Selected patient representatives from the patient advisory board (who have experience with chronic pain and opioids) and GPs affiliated with iamag participated in the development and pretesting of interview guidelines to ensure relevance and feasibility from both clinical and patient viewpoints. Both female and male patients and GPs were included to achieve a balanced gender representation.

In order to foster meaningful stakeholder engagement across all project stages, the research team employed the Involvement Matrix³⁶ in collaboration with key stakeholders to co-design and evaluate appropriate participation formats. Initiated in the run-up to Phase 1, this process allowed participants to specify both the project phases and the levels of involvement they deemed appropriate.²⁸

Consideration of Sex and Gender in Stakeholder Engagement

In selecting the project team and advisory board, we aimed to incorporate diverse perspectives regarding sex and gender. This was especially important when involving patients and physicians, in order to understand gender-specific experiences with healthcare, illness, and stigmatization. We offered a variety of formats (eg, individual interviews, group discussions, written exchanges) to accommodate different communication styles. In addition, we established the use of gender-sensitive language in both personal and written communication. At the end of the project, a reflection on these activities will inform future research initiatives.

Participatory Development of Intervention Modules

The intervention modules were derived from a collaboratively developed ToC and refined in close collaboration with relevant stakeholders, depending on the task and required expertise (please also see section “Theory of Change and application of middle-range theory”). Concepts for the individual intervention modules (eg, the Positive Health Dialogue) were co-developed in joint meetings with experts, GPs and patients.

Participatory Development and Piloting of Evaluation Tools

Based on the defined modules and expected outcomes, validated scales were selected and custom evaluation tools developed. Stakeholders participated in both the development (through workshops) and piloting (via think-aloud methods) of these tools.

Evidence-Based and Theory-Guided Development

Use of Established Frameworks

To ensure a systematic, theory-informed, and context-sensitive development of a sex- and gender-sensitive intervention for patients with CNCP in primary care, we followed the updated MRC Framework.³⁰ This approach enabled a structured development process, with particular emphasis on gender-specific aspects of healthcare and communication. A ToC was developed to conceptually underpin the intervention logic and formulate explicit assumptions about mechanisms of impact and contextual conditions. In Phase 2, both the MRC Framework and the feasibility criteria defined by Pearson et al²⁹ will guide further piloting and evaluation.

Creation of a Database for Intervention Development

We conducted a literature search in PubMed to gather contextual information and thematic evidence on the following topics:

1. Sex and gender-sensitive pharmacology
2. Comorbidities in chronic pain with regard to sex and gender
3. Sex and gender-specific aspects within relevant clinical guidelines
4. Non-pharmacological treatments for chronic pain
5. Doctor-patient communication with regard to sex and gender
6. Social support and chronic pain with regard to sex and gender

Our search was performed systematic (see Table A1 and Appendix 1), nevertheless it was not a formal systematic review with standardized quality assessment (eg, PRISMA/AMSTAR), but rather a foundational step for intervention development.

In parallel, we conducted semi-structured telephone interviews with seven patients and five GPs, exploring experiences with chronic pain management, opioid therapy, and expectations for a sex- and gender-sensitive intervention. The interview guides were developed collaboratively in workshops involving patients and GPs, together with the project team. Interviews were transcribed and analyzed using rapid qualitative analysis.³⁷ The rapid approach works with a pre-defined Excel matrix with seven deductive categories derived from the interview guide. Data were organized by a primary analyst and reviewed by a secondary analyst, with discrepancies discussed and resolved in regular team meetings, developing high-level summaries for each category. The analysis resulted in recommendations for intervention development. Our findings have been published elsewhere³⁸/are currently under review (Schmidt et al 2025).

Findings from both the reviews and interviews were discussed in multi-stakeholder workshops (advisory board, patient representatives from the iamag patient advisory board, project team) and informed the design and content of the intervention components (see Results).

Theory of Change and Application of Middle-Range Theory

The development of the GESCO intervention was guided by a collaboratively developed ToC,³⁹ serving as a planning and evaluation tool that visualizes the pathways from intervention activities to intended outcomes and long-term impacts.^31,40 In a moderated online workshop, the project team and the GESCO advisory board jointly defined a long-term vision and mapped backwards to define necessary goals, intermediate outcomes, outputs, and intervention activities. The process began with brainstorming, followed by the clustering of ideas and the development of preliminary causal pathways.

All components (goals, outcomes, outputs, activities, etc.) were documented on a Miro board (www.miro.com). Initial prioritizations and preliminary causal pathways were developed during the workshop. The project team subsequently reviewed and refined the ToC structure based on the approach by John Mayne,^32,41 which emphasizes Behavioral mechanisms of change resulting from the interaction of Capability (psychological/physical), Opportunity (social/physical), and Motivation (conscious/unconscious) (COM-B model).³³ These components were systematically linked to specific intervention elements to clarify how and why behavior change is expected. The drafted ToC was reviewed by the research team and refined through an advisory board consensus process.

Sustainability

Identification of Implementation Strategies

Based on the prior steps a multimodal implementation strategy was developed. The strategy aims to support feasibility and accounts for setting-specific requirements to facilitate later integration into routine care.

Laying the Foundation for the Pilot Study

This paper presents Phase 1 of the GESCO study, focused on intervention development. The results will form the basis for a pilot study. A detailed overview of the overall study design is provided in the study protocol.²⁸

Results

Based on the methodological approach described above, the following section presents the key outcomes of the intervention development process. These include the data basis for intervention development (derived from literature reviews and qualitative needs assessments), the resulting intervention components, the development of a tailored implementation strategy, and the collaboratively developed ToC.

Data Basis for Intervention Development (Literature Reviews and Qualitative Needs Assessments)

Literature Reviews

Literature reviews were conducted on topics relevant to the development of a sex- and gender-sensitive intervention. The following section presents our key findings:

Sex- and Gender-Sensitive Pharmacology

Research has revealed both qualitative and quantitative sex- and gender-specific differences in pain perception and chronification processes.^18,42 Distinct physiological variations in the nervous, hormonal, and immune systems contribute to these differences. Hormonal factors, particularly fluctuations in estrogen and progesterone, play a central role in modulating nociception. Estrogen, for example, has been shown to affect opioid receptor activity and increase pain sensitivity, potentially explaining cyclical pain patterns observed in women, whereas high progesterone levels contribute to less pain during childbirth.⁴³ In contrast, testosterone is often associated with elevated pain thresholds, contributing to sex-based differences in pain experiences.^18,42

The immune system also exhibits sex-specific characteristics. Both innate and adaptive immune responses are generally higher in females than in males, which can lead to increased production of pro-inflammatory cytokines potentially enhancing pain sensitivity and contributing to chronic pain conditions.⁴⁴

Clinical data confirm a higher prevalence of chronic pain in women.^18,42 Women tend to report higher pain intensity, experience pain more frequently and across a greater number of body regions, and endure pain for longer durations. Chronic pain conditions such as fibromyalgia, irritable bowel syndrome, and interstitial cystitis also have a higher prevalence in women.¹⁸ Furthermore, the effects of opioids differ between women and men: women are more likely to experience side effects such as nausea, dizziness, and respiratory depression, whereas men are more prone to develop addictive behavior when using opioids.^42,45,46

Comorbidities in Chronic Pain with Regard to Sex and Gender

Chronic pain is frequently accompanied by a wide range of comorbidities, particularly mental health disorders such as depression, anxiety, substance use disorders, suicidal ideation, and personality disorders, affecting both men and women.^47–52 Women more commonly present with comorbid depression, fatigue syndrome, and metabolic or cardiovascular conditions,^53–61 while men are more likely to experience sleep disturbances and substance use disorders.^51,62 Data from the BARMER Health Insurance indicate that nearly 80% of patients with CNCP and LTOT are exposed to polypharmacy, defined as the use of at least five different medications per day. The proportion is approximately 8% higher among females than males.²⁵ These gender-specific patterns suggest differing pathways and prognoses in chronic pain experiences, underscoring the importance of tailored interventions.^63–65

Sex- and Gender-Specific Aspects Within Relevant Clinical Guidelines

An analysis of eight full-text guidelines^8,61,66–71 showed that sex and gender are barely mentioned. In some guidelines, pregnant women are explicitly excluded from the target population.^69,71 In others opioids are listed as risks for pregnant women and their children.^8,70 Risks associated with LTOT, such as hormonal dysregulation affecting mood, sexual desire, and physical performance, are noted.⁷⁰ Some guidelines also report evidence suggesting a stronger association between substance use and male sex.⁶⁶ However, no concrete recommendations for care are derived from these observations.

Gender as a socio-cultural construct, including aspects such as gender roles or doctor–patient interactions, is entirely absent in the reviewed documents.^6,8,66–71 Pain perception, symptom presentation, and other potentially relevant sex/gender influences were not addressed. Guidelines do however increasingly recognize the multidimensional nature of health and illness, emphasizing resource-oriented care and quality of life as independent treatment goals.^8,66,68

Non-Pharmacological Treatments for Chronic Pain

Clinical guidelines emphasize the importance of psychological stress and past life events in shaping pain perception.⁶⁸ Individual therapeutic goals should be developed in collaboration with the patient.⁶⁶ In this context, the guidelines provide recommendations for non-pharmacological therapies. These include physical activity therapies (eg, yoga),^67,69 cognitive behavioral therapy,^67–69 activating interventions, and stress management techniques.⁶⁸ These elements can be combined within multimodal treatment approaches.

Research shows that non-pharmacological therapies are evidence-based and effective but often underused.⁷² Barriers to non-pharmacological therapies include high costs, transportation issues, low motivation, and patient skepticism, especially when opioid therapy has already been initiated. Enabling factors include offering a range of therapy options, team-based primary care, and a structured follow-up of multimodal pain management by healthcare providers.⁷³

Doctor–Patient Communication with Regard to Sex and Gender

Effective doctor–patient communication, particularly when characterized by empathy and a person-centered approach, has been shown to improve treatment outcomes, increase patient satisfaction, support emotional well-being, and enhance adherence.^11,74,75 Sex and gender significantly impact how pain is perceived, expressed, and managed, thus influencing diagnostic and therapeutic decisions. Nevertheless, gender-specific considerations remain largely absent from clinical education.^74,76 In the context of chronic pain management, especially when opioids are prescribed, uncertainty regarding expectations between doctors and patients can strain communication and erode trust. It is therefore essential to promote an open, empathetic dialogue to address concerns related to misuse, dependency, and potential alternatives.^77,78

Sex and gender dynamics within doctor–patient dyads can also shape communication patterns. Female doctors are generally more likely to engage in empathetic, patient-centered communication styles, although this tendency often goes unrecognized or underappreciated in clinical settings.^75,79 While the evidence as to whether doctor or patient gender exerts a stronger influence remains inconclusive, research indicates that female patients tend to be more actively engaged and participatory in clinical interactions.^80,81

Social Support and Chronic Pain with Regard to Sex and Gender

Social systems play a significant role in shaping pain perception, coping strategies, and the experience of disability among individuals with chronic pain. These influences are mediated by personal characteristics such as sex, gender, and cultural background. For example, depressive symptoms in men are more strongly associated with dissatisfaction in social roles compared to women,⁸² and men and women tend to prioritize different aspects of social life in their coping processes.⁸³

Positive social integration and the inclusion of partners or family members in treatment are associated with pain reduction and improved quality of life.^84,85 In contrast, strained social environments, limited emotional support, and exposure to trauma are linked to increased pain intensity, greater functional impairment, and heightened emotional distress.^86,87 Social stressors also affect opioid therapy outcomes. For instance, anxious partner responses and low perceived social support are associated with higher opioid doses and an increased risk of opioid use disorder.^88,89 A lack of family and social support is a key risk factor for opioid overdose.⁹⁰

Qualitative Needs Assessment

To complement our data basis for intervention development, we conducted semi-structured telephone interviews with patients and general practitioners, focusing on their experiences with CNCP and LTOT as well as their needs and preferences regarding a sex- and gender-sensitive intervention in this field.

We interviewed seven patients (six female, one male, aged 35–68), all living with CNCP and experienced with LTOT (Schmidt et al 2025 (currently under review)). Key findings highlight that chronic pain is pervasive, severely affecting daily life, sleep, and social participation. Stigmatization and social withdrawal were common, and LTOT was seen as both relieving and burdensome due to side effects and lack of patient understanding. Non-pharmacological treatments were appreciated but often difficult to access. Physician–patient relationships varied, with trust and communication playing central roles, though many patients felt misunderstood or solely responsible for access to therapy opportunities and expressed a lack of hope for improvement in their therapies. While sex/gender was not always explicitly recognized, some experiences suggested it influenced empathy and communication.

In parallel we interviewed five GPs. Two of the participants were women and three were men, with ages ranging from 45 to 70 years and professional experience ranging from 18 to 43 years.³⁸ Findings underscore the central role of GPs in long-term pain management, particularly through their enduring therapeutic relationships with patients. However, GPs face recurring challenges, such as unmet expectations, limited treatment options, and concerns about addiction, which can lead to emotional strain, countertransference, and impaired communication. Maintaining empathetic, trust-based relationships was seen as essential for effective care. Sex and gender were identified as relevant influences on patient-provider interactions. While some GPs aimed to treat all patients impartially, gender stereotypes and interpersonal dynamics, such as same-gender trust or communication styles, often shaped clinical encounters. Female GPs reported more emotional openness and awareness of internal conflict. All participants noted the lack of formal training in gender-sensitive medicine and pharmacology but recognized its importance for equitable care.³⁸

Implications for Intervention Development

Based on our literature reviews, we were able to derive the following implications for our intervention and implementation strategy: Evidence suggests that sex-specific pharmacological differences can be clinically significant, highlighting the importance of re-evaluating patients’ long-term medication, even after extended treatment periods. GPs should receive targeted training in this regard. While German and international guidelines on chronic pain and opioid therapy provide essential standards, sex and gender aspects are not yet consistently integrated. This suggests a potential role for structured approaches like GESCO to bridge these gaps. Furthermore, existing guidelines emphasize the importance of setting individualized treatment goals and integrating non-pharmacological approaches into care. In this context, the consideration of sex and gender aspects may may offer further refinement, thereby reinforcing their clinical relevance. As communication is a cornerstone of this process, fostering a heightened awareness of gender-related influences and including social support systems could contribute to more holistic and improved clinical outcomes. The insights from our interviews with patients led us to the following recommendations for the intervention development, which support the results from the literature reviews:

The intervention should strengthen GPs’ knowledge and communication skills, particularly regarding LTOT, non-pharmacological options, and empathetic, shared decision-making. It should improve access to and coordination of multimodal care, support patient self-management through clear information and resources, and promote critical reflection on the role of sex and gender in clinical interactions. Self-reflection enables GPs to recognize their own biases and assumptions, fostering more empathetic care and reducing stigma. Additionally, addressing the biopsychosocial impact of chronic pain, such as stigma, isolation, and mental health, is essential to provide patient-centered care.

Following our GP interviews, key recommendations for the intervention development include the need for longer, appropriately reimbursed consultation times to enable person-centered care; comprehensive medical histories that consider biological, psychological, and social factors; and enhanced training in general pain management, gender-sensitive approaches, and pharmacotherapy. Additional priorities identified were regular case discussions to support professional exchange, improved access to regional psychosocial support services, and the development of better diagnostic tools to assess pain and patients’ social contexts. Emphasis was also placed on promoting patient collaboration, empathetic communication, and the implementation of a biopsychosocial model to address the complex nature of CNCP. Tailoring interventions to sex- and gender-specific needs, like adapting communication styles and therapeutic goals, is considered essential.³⁸

Theory of Change

To understand the potential effects and change mechanisms of the GESCO intervention, we developed a ToC, of which the current version is shown in Figure 1. Below, we describe our ToC from bottom to top. Furthermore, the ToC provides indications of how the described changes are to be measured, thereby bridging the gap to the evaluation of the intervention (which will be published separately).

Figure 1 The GESCO Theory of Change. Notes: Light red = Input and implementation strategy, Lilac = Reach, Green = Capacity changes, Light green = Behavior changes, Yellow = Outcomes, Boxes on the right-hand side = Assumptions, Boxes on the left-hand side = External context.

Implementation Strategy/Intervention Resources (Input)

The GESCO training for the GPs starts shortly after the initiation visit by the project team and consists of six modules (see also sections Intervention and Implementation). . Upon completion of the training, GPs are asked to conduct two GESCO consultations with patients (intervention) and to document the tools and materials used for evaluation purposes.

Reach

Reach requires that the target patient group is appropriately defined, can be recruited, and is accessible. The project concept must appear meaningful to patients (and, if applicable, to their relatives) in order to motivate participation. Where relevant, the study may address the patients’ social environment and potentially include it in the consultation process. This, in turn, requires openness and willingness on the side of the patients. All materials and evaluation instruments must be comprehensible. The practice team supports all related activities.

GP Capacity Changes

Applying the COM-B model to the development of GESCO, GPs have increased awareness of their own gender stereotypes and behavior and have acquired new knowledge and skills in the context of the GESCO training (Capability). They are open-minded, change-ready, and offer a setting in which behavioral change is possible, eg, based on resource-oriented interventions (Opportunity). GPs feel confident in applying newly acquired skills and tools which they perceive as meaningful and appropriate (Motivation).

Supporting activities help to consolidate new knowledge and skills and initiate further reflection processes, which promote sustained changes in attitudes and motivation.

When changes in patients are perceived, such as improvements in the doctor–patient relationship (> outcome), this has a reinforcing effect on capacity and behavior changes (> output).

GPs and Patient Behavior Changes

Behavior changes refer to the specific, measurable changes in clinical practice³² that occur as GPs begin to apply their newly acquired communication techniques, assessment tools, knowledge regarding medication, gender, and comorbidities, as well as referrals to psychosocial support services.

A key prerequisite for sustained behavior change is the practicability of the intervention activities. Working with the intervention may also increase GPs’ awareness of their own stereotypes and potentially stigmatizing behaviors, thereby fostering to a more sensitive and reflective approach in clinical encounters. Over time, practices, attitudes, and knowledge gradually become internalized and integrated into routine care. Thus, a dynamic interaction emerges between capacity changes and behavior changes. The validated Normalization Measure Development Questionnaire (NoMAD)^91,92 serves evaluation purposes assessing the degree to which a new practice becomes implemented in routine care.

Another key prerequisite for sustainable change is the perception that the change leads to meaningful improvement. The validated ORIC scale distinguishes between two domains: change commitment and change efficacy (completed in this study by the GP as a proxy for the organization). When the commitment to change is high, members of the organization are more likely to invest in change efforts and demonstrate greater motivation to overcome obstacles.⁹³

Supporting Activities/Implementation Strategy

To ensure sustainability of the intervention, several supportive measures will be implemented. A toolbox and accompanying materials provide ongoing access to the knowledge and techniques acquired during training. In addition, a case conference eight weeks after the training offers room for questions and in-depth practice of communication skills, allowing participating GPs to exchange experiences and discuss specific cases. A quality circle provides longitudinal support for GPs. Moreover, a patient brochure is designed to strengthen patient empowerment, thereby reinforcing the intervention’s overall impact.

Intermediate Change (Outcome)

The intervention generates effects on multiple levels: For GPs, it fosters a better understanding and knowledge of their patients and their individual circumstances (1), thereby strengthening the doctor–patient relationship (2). Patients receive more appropriate pharmacotherapy (2) and better information and education (5). The GESCO intervention may also improve physical functioning (3). Furthermore, new treatment impulses promote the activation of personal resources and improved self-management (6), which in turn enhances pain acceptance (4). The integration of the patient’s social environment into treatment further increases acceptance of their situation (7,8).

To assess these effects, qualitative interviews will be conducted as part of the process evaluation. Furthermore, selected validated measurement scales will complement the evaluation: The Marburg Questionnaire on Habitual Well-being (FW7),⁹⁴ the Internalized Stigma of Chronic Pain Scale (ISCP),⁹⁵ and the Optimism-Pessimism Short Scale 2 (SOP2).⁹⁶ In addition, changes in medication and the Satisfaction with Information about Medicines Scale (SIMS)^97,98 and the Pain Medication Questionnaire (PMQ)⁹⁹ will be documented. Further details on data collection are provided in the study protocol.²⁸

Long-Term Change (Outcome)

In the long term, the GESCO intervention aims to support patients in achieving an improved quality of life and leading an active, self-determined life — goals that were identified as key priorities during our participatory Theory of Change (ToC) workshop. This orientation aligns with current clinical guidelines, which recognize the multidimensional nature of health and illness. These guidelines underscore the importance of quality of life as a treatment objective, rather than merely addressing symptoms.^8,66,68

In study phase 2 (pilot study) quality of life will be measured using the Veterans RAND 12-Item Health Survey (VR-12),^100,101 which is part of the German Pain Questionnaire.¹⁰² The aspect of an active and self-determined life will be through the Pain Disability Index (PDI), which assesses impairments in daily life activities.¹⁰³

External Influences

External influences may significantly affect the intervention and lead to unintended effects. Examples include the accessibility of psychosocial services, updates to clinical guidelines, or legislative changes. Time constraints and reimbursement structures may also represent critical barriers. During the pilot study (phase 2), several anticipated implementation challenges will therefore be explicitly monitored.

First, we provide a structured “GESCO toolbox” to streamline the consultation process and will document the actual time spent to inform future discussions on reimbursement.

Second, structural inequalities in access to regional support services may influence the intervention’s effectiveness. We address this by providing a comprehensive directory of services. By incorporating these factors into our process evaluation (eg, via GP interviews and NoMAD scales), we aim to differentiate between the intervention’s inherent performance and the influence of systemic external constraints.

Intervention Components

Building on the findings outlined in the previous section, we developed the GESCO intervention using a participatory approach. Biological, psychological and social dimensions of chronic pain, LTOT and sex and gender were considered when selecting concrete measures (such as “Positive Health”) through an iterative process. This involved a series of workshops and consultations with key stakeholders, including an Advisory Board of clinical experts and patient representatives. Reflecting the reinforcing dynamics identified in our Theory of Change, the resulting intervention is a structured, multi-component conversational program delivered over two GP consultations, designed to introduce new therapeutic impulses.

The first consultation focuses on expectation management in order to foster meaningful, patient-driven goal setting as the basis for individualized care. Figure 2 displays a pocket card we developed to support GPs during the consultation.

Figure 2 GESCO consultation 1 (pocket card for GPs).

During the first GESCO consultation the patient is invited to engage in a conversation outside the typical routine. Using narrative medicine techniques, the patient’s biography is explored with particular attention to gender-related aspects. Inherent narratives or belief systems held by the patient are identified, potentially opening new dimensions in the doctor–patient relationship. A biographical reference of this kind could include, for example, the belief that one must not show pain in order to embody strength and, potentially, masculinity. In such cases, chronic pain is often accompanied by feelings of shame. The physician acknowledges this narrative (eg, “You have learned that persevering signifies strength”), while simultaneously creating space for a new understanding of resilience that incorporates self-care. Another example is a perceived duty of care, which can imply the belief that one’s own needs must be secondary to those of others. Here, chronic pain may be closely linked to feelings of guilt. Through narrative techniques, the theme of “self-worth” can be re-explored and redefined.

Additionally, during the first consultation medication use is reviewed. The insights gained from the conversation and the medication review serve as the foundation for jointly defining expectations and therapeutic goals. It is essential that patients formulate their goals autonomously, guided by their own priorities. A follow-up consultation is scheduled, during which these goals are revisited.

Consultation 2 takes place six to eight weeks after Consultation 1. The focus here is on patient empowerment (see Figure 3). First, the progress since the first conversation is discussed, and the patient is invited to engage in the second conversation. Next, the patient completes the “Spider Web”, a dialogue tool from the Positive Health approach (see Figure 4).

Figure 3 GESCO consultation 2 (pocket card for GPs).

Figure 4 Positive Health dialogue tool (https://positivehealth-international.com/wp-content/uploads/2024/07/PHI-Dialogue-tool-ADULTS-2.0-ENGLISH-DEF-20240701.pdf [July 2025]).

Positive Health is a salutogenic concept developed by Machteld Huber that encompasses six interacting dimensions of health: bodily functions, mental well-being, meaningfulness, quality of life, participation, and daily functioning.^104–106 These dimensions are assessed by mapping the patient’s current condition on that day using the positive health tool (spider web), which facilitates a patient-centered dialogue focusing on health potentials and resources. Within this dialogue, patients can formulate goals and identify desired next steps.¹⁰⁶

Depending on the direction the dialogue takes, additional tools may be introduced: Social network diagnostics (see Figure 5) to address the involvement of relatives;^107,108 the German Pain Questionnaire¹⁰² as supplementary anamnesis information; and a list of regional support services to facilitate concrete interventions. Additionally, the GESCO patient brochure can be handed out to provide patients with information about chronic pain and sex/gender aspects (please see section Implementation strategy for more information regarding additional tools). At the end of the consultation, next steps can be discussed and a follow-up appointment scheduled (which is no longer part of the intervention). Both GESCO consultations last approximately 30 minutes each.

Figure 5 Personal Social Network Mapping Tool as part of the GESCO intervention (Based on Hunger et al 2019).107

Implementation Strategy

The implementation of a complex intervention requires a multimodal implementation strategy.^109,110 In the case of GESCO, this strategy comprises four key components: an initiation visit, a two-day training program for GPs, supportive materials and activities, and a case conference aimed at reinforcing what has been learned. The following section outlines each of these elements in more detail.

Initiation Visit by the Project Team at the Study Practice

Before the project begins, each participating practice is visited by the project team. A personal introduction is important to establish a solid foundation for collaboration. The project is presented with a particular focus on the implementation of data collection and project-specific processes. The goal is to build capacity, increase readiness, and identify potential barriers to successful implementation.

Educational Training for General Practitioners

A two-day training program for GPs was conducted, consisting of an introduction and six education modules. The introduction helped foster relationship-building within the group and clarify experiences and expectations, thereby acknowledging existing resources and empowering the physicians. Thereafter, the following modules were covered:

1. Introduction to Gender-Sensitive Medicine: This module provides foundational knowledge of gender-sensitive medicine. Participants reflect on their own stereotypes through a group exercise.
2. Therapeutic Goals and Expectation Management: Applying biographical approaches (eg, narrative medicine) with a focus on gender, this module aims to stimulate new impulses for treatment and challenge established routines.
3. Sex and Gender-Sensitive Pharmacology: Participants receive evidence-based information on sex-specific differences in opioid effects, reflect on the use of assessments, and discuss re-evaluation of current medication regimes. Additional topics include deprescribing and drug therapy safety.
4. Empowerment: This module focuses on activating patient resources and promoting self-management strategies.
5. Non-Pharmacological Treatment Options: Participants explore which options, beyond opioids, can support improvements in patients’ quality of life.
6. Extended Medical History: This final module addresses which additional information or assessments may help support the above aspects and contribute to achieving revised therapeutic goals.

Figure 6 presents the six training modules alongside the expected changes/outputs in GP consultations and the related supporting activities.

Figure 6 Overview of GESCO training modules for GPs, expected outputs in GP consultation and supporting activities.

Supporting Activities

To support the implementation of the GESCO intervention, several materials were co-developed and piloted by our advisory board:

1. GESCO pocket cards: The pocket cards provide a practical overview of the structure of the two GESCO consultations. They support the GP in delivering the intervention.
2. The GESCO Toolbox: The GESCO Toolbox serves as a reference guide for GPs. It allows them to revisit and consolidate the knowledge acquired during the educational training. Each training module is clearly linked to relevant tools, which are visually highlighted for easy navigation. For example, the “Positive Health Spider Web” is prominently featured in the Empowerment module.
3. Manual on Gender-Sensitive Pharmacological Therapy: Given the central role of pharmacotherapy in this project, we developed a dedicated manual. It provides practical guidance on sex- and gender-sensitive opioid prescribing, including safety aspects, deprescribing, and the use of assessment tools.
4. Directory of Psychosocial Support Services: Each participating practice receives a regionally tailored list of psychosocial and psychological support services to facilitate referrals and interdisciplinary care.
5. Patient Information Brochure: This brochure offers patients accessible information on chronic pain and the relevance of sex and gender. It also includes suggestions for preparing for their GP consultations, as well as an illustrative case story. The brochure provides the patient with relevant information, strengthens empowerment, and supports the intervention.

Case Conference

Approximately eight weeks after the training, all participating GPs meet online for a follow-up session. This case conference provides an opportunity to clarify questions regarding the application of newly learned techniques or assessments. It also provides room for the joint discussion of selected patient cases.

Furthermore, we plan to establish a cross-project online quality circle for GPs, which will meet quarterly to foster continued exchange and learning.

Discussion

The GESCO intervention addresses a significant gap in the primary care management of patients with CNCP and LTOT by introducing a gender-sensitive, biopsychosocial consultation approach. Its design reflects the systematic integration of evidence-informed components into everyday general practice.

With the GESCO consultation, we address patients’ desire for improved communication among physicians, particularly in the area of shared decision-making (see interview results). At the same time, we align with current guideline recommendations by promoting the development of individualized therapeutic goals and incorporating patients’ biographies^66,68 (see literature review on clinical guidelines). Our interviews with GPs showed that sex- and gender-sensitive medicine and pharmacology was not part of their medical training and continuing education.³⁸ This is noteworthy, as research strongly recommends targeted training and ongoing professional development in gender-sensitive pain management to prevent the marginalization of patients and to foster a more comprehensive understanding of chronic pain experiences.^16,74,111 Despite not yet being standard, gender-sensitive medicine in Germany is gaining traction through new academic initiatives^112,113 and a planned 2025 reform to medical licensing regulations that will mandate its inclusion in medical training.¹¹⁴ Internationally, numerous efforts are also being made to develop or revise curricula in the field of sex- and gender-sensitive medicine.^115,116 This underscores the potential value of including sex- and gender-sensitive medicine and pharmacology in a GP training program such as GESCO. Additionally, the intervention seeks to facilitate more in-depth dialogue by offering extended consultation times, addressing a need often reported as unmet in routine GP care.³⁸

Evidence highlights the value of social systems as important resources in the management of chronic pain,^84,85 which led us to incorporate social network diagnostics into the intervention.¹⁰⁷ Additionally, the Positive Health concept allows for a holistic understanding of patients’ needs and overall life situation.^104,106 The fact that established pain guidelines do not yet address gender-sensitive care^8,61,66–71 suggests a potential gap in current clinical practice which the GESCO intervention aims to address. We also build on existing recommendations for multimodal treatment^68,69,72,73 by including a directory of regional psychosocial support services. Overall, the GESCO intervention aims to align with international calls for person-centered and multimodal pain management strategies, particularly in light of increasing concerns about the long-term use and risks of opioids in chronic pain.^4–7

A core strength of the GESCO intervention lies in its structured yet flexible consultation format, which supports GPs in engaging patients beyond routine prescription management. The inclusion of narrative techniques and tools such as the Positive Health spider web¹⁰⁶ facilitates a deeper understanding of patients’ lived experiences, social contexts, and gendered health narratives. This person-centered approach may contribute to strengthening therapeutic relationships, enhancing patient activation, and promoting treatment goals that are meaningful and realistic from the patient’s perspective.

By anchoring the intervention within the COM-B informed Theory of Change, GESCO provides a transparent rationale for how behavioral change is expected to occur. This theoretical grounding supports both the implementation and the subsequent evaluation of mechanisms and outcomes.^117–119 The updated MRC Framework explicitly recommends conducting a Theory of Change (ToC).³⁰

A recent study among German GPs showed that they face challenges in implementing clinical guidelines related to opioid therapy in their daily practice.¹²⁰ This suggests that successful implementation may require a structured, multifaceted strategy, such as the one we offer with GESCO. Nevertheless, sustainable change takes time, and the limited project duration may therefore not be sufficient to capture all effects (eg, normalization as measured by the NoMAD).^91,121 On the patient side, the intervention’s multi-dimensional effects, ranging from increased self-management and optimized medication to improved empowerment, address critical outcome domains for chronic pain care. The GESCO approach is designed to be adaptable to diverse patient profiles. For instance, the use of visual tools like the “Positive Health” spider web facilitates engagement for patients with lower health literacy or those with complex psychosocial needs by simplifying abstract health dimensions. Importantly, the long-term aims of improving quality of life and enabling a self-determined life reflect the priorities identified in the participatory workshops and are consistent with international quality standards in pain management: Quality of life is recommended as a key outcome parameter for evaluating pain management interventions.¹²² The VR-12 has been shown to be a suitable instrument for measuring quality of life in patients with chronic pain.¹²³ Nevertheless, we assume that this is a long-term outcome and that it may not fully unfold within the timeframe of the short-term feasibility study. To bridge this gap and sustain improvements beyond the intervention period, community-based social support services and digital health services have the potential to complement primary care, thereby fostering long-term treatment effects.^124,125

Nevertheless, several challenges remain. The integration of new practices into routine care requires time, resources, and team-level commitment. While GESCO attempts to address this through supportive measures (eg, toolbox, training, case conference), long-term sustainability may depend on broader systemic factors, such as reimbursement structures and guideline alignment. Additionally, the intervention’s effects may be moderated by external influences (eg, access to services, policy changes), which must be accounted for in outcome interpretation.

Regarding the generalizability of GESCO, the intervention was designed with a low-threshold and modular structure to foster its applicability beyond specialized or high-resource environments. By focusing on structured communication and narrative tools (eg, Positive Health) rather than expensive infrastructure or specialized equipment, the approach is highly adaptable to different primary care settings.

Future studies should explore the scalability and adaptability of the intervention across diverse practice settings. Moreover, the role of intersectional factors, such as age, migration background, and socio-economic status on patients’ experiences and responses to the intervention warrants more in-depth exploration.¹⁵ Currently, the intervention provides limited formal guidance on these intersecting dimensions, representing a gap that future studies may address. To enhance scalability and equity, subsequent adaptations could include specific modules or flexible conversation flows that better meet the needs of patients facing multiple forms of marginalization. Nonetheless, patients already benefit as gender-sensitized GPs develop a more reflexive, person-centered approach. This foundational sensitivity fosters an inclusive environment that enhances care for diverse patient groups, even before other intersectional dimensions are formally integrated. Additionally, research processes themselves, such as data collection and interpretation, are subject to a certain degree of gender and diversity bias, which can influence scientific progress and reinforce societal stigma.^15,126 This underscores the need for continuous self-reflection within the research team.

Strengths and Limitations

A key strength of the GESCO intervention is its theoretical foundation, combining the COM-B model with a participatory ToC process. This ensures transparency in the assumed mechanisms of change and enables the systematic evaluation of both implementation and outcomes. The intervention is pragmatically designed for routine general practice, with structured yet flexible consultation modules that can be adapted to individual patient needs. The development process was participatory and included input from practitioners and patients, thus enhancing relevance, feasibility, and acceptability in real-world settings.

The comprehensive training program and additional resources (eg, pocket cards, toolbox, pharmacotherapy manual) support knowledge transfer and help sustain behavior change. Furthermore, GESCO explicitly integrates gender-sensitive medicine, a domain often underrepresented in primary care interventions, especially in the context of chronic pain and opioid therapy. By addressing sex and gender as both a biological and psychosocial determinant of health, GESCO contributes to more equitable care.

Despite its strengths, several limitations must be acknowledged. First, the intervention’s reliance on motivated GPs who may have more time at their disposal may limit its generalizability to practices with high workloads or staffing constraints. The consultations are longer than standard GP appointments, which may present structural and financial barriers to implementation. But, in terms of practical implementation, certain existing billing codes in Germany already facilitate extended consultations (eg, within Disease Management Programs (DMP)). The GESCO intervention can build upon these established structures. Furthermore, frequent attenders might benefit from these more intensive consultations in a way that reduces their overall frequency of visits in the long term, because the intervention fosters their self-activation / empowerment. This, in turn, can support the practicability of the intervention.

Second, while the intervention aims to address a complex condition holistically, its success may depend on external system factors, such as the availability of psychosocial support services or continuity of care, which are not controlled within the intervention but may influence outcomes.

Finally, while gender sensitivity is a core component, intersectional aspects, such as the interaction of gender with socio-economic status, ethnicity, or age, are not yet fully integrated into the intervention design and should be considered in future adaptations.

Conclusion

In conclusion, GESCO represents a promising, theory-driven approach that aims to support improvements in chronic pain care processes in primary care settings. By combining gender sensitivity with a structured, resource-supported consultation model, it holds the potential to foster more reflective, individualized, and empowering care processes for patients with complex chronic pain histories. Its strong theoretical foundation, participatory development process, and comprehensive training program enhance its relevance and feasibility for real-world implementation. However, challenges remain regarding its implementation in general practices, including systemic barriers such as time constraints, workload pressures, reimbursement structures, and limited access to external support services, as well as its dependence on such services. In addition, there is a need to further incorporate intersectional factors beyond gender, such as socioeconomic status, migration background, or educational level, which can substantially shape patients’ access to care, communication with healthcare providers, and experiences of chronic pain. Future research will need to explore the scalability, long-term outcomes, and the intervention’s adaptability to diverse patient populations and healthcare settings. Overall, GESCO has the potential to foster more reflective, empowering, and equitable chronic pain care aligned with international clinical standards. In the next project phase, the participatorily developed GESCO intervention will be piloted in ten general practices with a total of 40 patients using an effectiveness–hybrid design²⁸ with a focus on feasibility criteria²⁹ and preliminary effects.