In collaboration with a European Reference Network for rare diseases, we aimed to identify red flags for the diagnosis of rare and complex connective tissue and musculoskeletal diseases (rCTDs). Some indicators, presented as red flags, might raise clinicians’ awareness about the presence of rCTDs. Their identification is critical in primary care, where they are most likely to be first observed.

Firstly, we conducted a scoping review to identify red flags already published in the scientific literature. We included studies about people with rCTDs that described red flags, warning signs, alarm symptoms, and pathognomonic signs identifiable in a primary care setting. Then, we conducted a systematic review of evidence pointing out which signs and symptoms should arouse suspicion specifically for IgG4-related disease. We included studies providing estimates of diagnostic precision or prevalence of signs and symptoms, and we assessed their quality and applicability to the review question. We conducted systematic searches in major medical databases and manual searches in rare disease resources.

For the scoping review, 49 studies out of 1,656 records met the inclusion criteria. Two reported red flags for autoimmune diseases altogether, and 14 described red flags for systemic sclerosis. For the systematic review, seven studies out of 4,477 records met the criteria, comprising five diagnostic precision studies and two large case series. These were generally rated as having a high risk of bias and were included as indirect evidence. We identified 32 potential IgG4-related disease red flags, 10 related to clinical history findings and basic signs or symptoms, and eight belonging to common laboratory findings and basic imaging techniques.

Red flags for rCTDs have generally been established through expert consensus and lack valid indicators for diagnosis, such as sensitivity, specificity, or predictive values. They frequently overlap among different rCTDs. Potential red flags are prone to change as further evidence emerges. This shows the need to collaborate with reference networks to address rare diseases where the evidence is still scarce.

A consortium of five Spanish health technology assessment (HTA) agencies conducted the European Reference Networks Guidelines Programme for the development, appraisal, and implementation of clinical practice guidelines aiming to support clinical decision-making in the field of rare diseases (RDs). In response to this objective, methodologists and information specialists conducted systematic reviews (SRs). This study aims to explore the barriers/facilitators they encountered.

A survey was designed to elicit HTA agencies’ experience in developing SRs on RDs. Information was collected on the number of SRs conducted and the types of RDs and clinical questions addressed. In addition, they were asked to identify barriers and facilitators for each stage of the review (from the definition of PICO [population, intervention, comparator, outcome] components of the question to the issuing of recommendations). Finally, they were asked for process improvement suggestions. The survey was distributed by email and completed online. A thematic analysis was conducted to identify the issues identified at each stage of SR.

A total of 111 SRs were conducted on 35 RDs. Most clinical questions were about diagnosis and treatment. The main barriers identified were lack of MesH (Medical Subject Headings) terms associated with the conditions, non-representative abstracts and keywords, lack of relevant information in the body of the articles, and reported data not allowing for quantitative syntheses or recommendations to be made. Facilitating aspects included Orphanet’s specific source of RD documents and having expert clinicians in the working groups who were also involved in all steps of the SR.

Conducting SRs in the field of RDs is challenging. Authors of primary studies are encouraged to be more exhaustive in reporting the results. More research focused on the SR methodology in RDs is necessary to address their particular characteristics and obtain robust results. It is crucial to collaborate with reference networks to address RDs, where the evidence is scarce.

Patients have knowledge, perspectives and experiences that are unique and can make an essential contribution to Health Technology Assessment (HTA). However, in order for their participation to be effective, they need to be able to understand how HTA reports are generated and the decision-making processes that they inform. The aim is to describe the development and virtualization of training materials for patients, as well as to their implementation in a pilot study.

A working group from Spanish Network of Agencies for Assessing National Health System Technologies and Performance (RedETS) agencies was created to develop educational materials in collaboration with patients. The content was based on international initiatives and feedback from the working group. The project was initiated in November 2020. The team consisted of HTA researchers, technicians with experience in training and virtualization and patients. The final version was obtained after an iterative process and refinement of the content and design.

The materials were published in complete and summary versions, and they were translated into Catalan, Basque and Galician. The online course was designed in an e-learning platform (Moodle) with the aim of being implemented by each of the agencies. The materials include relevant and summarized information on HTA processes, current framework at national and European level, and the role of patients in HTA. Health research and the importance of qualitative and quantitative methods are also addressed. The course also includes a module of practical aspects of patient and citizen participation for achieving an effective contribution to HTA. The course is being piloted with patients in different regions in Spain. The objective of the pilot is to evaluate the usefulness and satisfaction with the course, and it has been designed with the purpose of incorporating the pertinent modifications in the course.

The online training course is intended to facilitate the acquisition of knowledge related to the processes and tools of HTA for patients, as well as to inform them in what phases and in what way they can participate. The pilot will provide relevant information on its use in practice. It is expected that the course will favor capacity building and patient involvement.

To develop an international template to support patient submissions in Health Technology Assessments (HTAs). This was to be based on the experience and feedback from the implementation and use of the Scottish Medicines Consortium's (SMC) Summary Information for Patient Groups (SIP).

To gather feedback on the SMC experience, web-based surveys were conducted with pharmaceutical companies and patient groups familiar with the SMC SIP. Semistructured interviews with representatives from HTA bodies were undertaken, along with patient group discussions with those less familiar with the SIP, to explore issues around the approach. These qualitative data informed the development of an international SIP template.

Survey data indicated that 82 percent (18 of 22 respondents) of pharmaceutical company representatives felt that the SIP was worthwhile; 88 percent (15/17) of patient group respondents found the SIP helpful. Both groups highlighted the need for additional support and guidance around plain language summaries. Further suggestions included provision of a glossary of terms and cost-effectiveness information. Patient group interviews supported the survey findings and led to the development of a new template. HTA bodies raised potential challenges around buy-in, timing, and bias connected to the SIP approach.

The international SIP template is another approach to support deliberative processes in HTA. Although challenges remain around writing summaries for lay audiences, along with feasibility considerations for HTA bodies, the SIP approach should support more meaningful patient involvement in HTAs.

The Spanish Network of Agencies for Assessing National Health System Technologies and Performance (RedETS) defined a patient involvement (PI) framework for health technology assessment (HTA) activities in 2016. The aim of this study is to evaluate the process and impact of those PI initiatives that were implemented in the first year following the publication of this new framework.

A survey was sent to those HTA researchers who implemented PI in RedETS projects. Responses were reviewed by two authors. An adapted thematic analysis was performed and the results were later discussed by all authors.

Six responses from six agencies/units were analyzed. The objectives of PI initiatives were the following: inclusion of patient perspectives, preferences and values; elicitation of important health outcomes measures; and barriers, facilitators, or suggestions for implementation. Different methods were used for PI: surveys, focus groups, in depth interviews, and participation in an expert panel. Five main themes emerged: (i) challenges with the recruitment process, (ii) needs identified, (iii) impact of PI, (iv) lessons learned, and (v) suggestions for the future.

PI initiatives within the RedETS framework were tailored to each HTA project, its specific goals and the individual needs and resources of each HTA agency. The results also pointed out how PI has a relevant impact that has enriched RedETS products providing key information on experiences, values, and preferences of patients, contributions that benefit the HTA and the process of drawing up recommendations. The main challenges were related to recruitment processes and capacity building.

In December 2017, a patient involvement (PI) Interest Group was created in the Spanish Network of Agencies for Assessing National Health System Technologies and Performance (RedETS) Annual conference. It started as a voluntary group of health technology assessment (HTA) methodologists interested in PI. The objective of the Group is to promote and facilitate PI in HTA. With the support of the Spanish Ministry of Health and the RedETS Council the Interest Group grew to at least one member for each of the eight RedETS regional agencies and units. It currently has 22 members. The PI Interest Group works in periodic online meetings and an annual offline meeting to establish a space for experiences exchange and reach consensus on main issues regarding PI.

RedETS published a strategy to facilitate effective and efficient PI in HTA processes in 2017. The long-term objective is to mainstream PI in all RedETS products. This strategy was built on a literature review and a qualitative study with semi-structured interviews. The interviews detected capacity building needs for technicians and methodologist in the network to be able to actively engage patients in HTA reports.

Since the kick-off meeting the PI Interest Group has worked in a number of activities. The main lines of action since its creation were: (i) evaluation of PI process in RedETS HTA reports in 2017 and in current reports, (ii) discussion on main methodological and procedural aspects, and feasibility of different patient participation approaches, (iii) development of technical protocols and templates to facilitate PI, (iv) the creation/adaptation of educational materials for patients and (v) translation of the HTAi Glossary for patients to Spanish.

Peer-to-peer learning processes can foster technical capacity of HTA methodologist in the Spanish HTA Network and may favor the implementation of the PI strategy.