Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis.

OBJECTIVE: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS: 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.

A systematic review of the early dialogue frameworks used within health technology assessment and their actual adoption from HTA agencies.

Introduction: Early advice in the process of developing health technologies allows manufacturers to plan their production and transfer to health care systems more accurately. This review aims to describe frameworks used within HTA and their current use by HTA Agencies. Material and methods: We carried out a systematic literature review in Pubmed, Embase, Scopus, and WoS, including all references published in Spanish and English. This was last updated in March 2022. We extracted all available information regarding the organizations involved, services offered, types of technology, collaborators involved, fees, output and impact. Websites of several HTA organizations and Google were also searched in order to update and complete the information obtained from this generic search. Results: Five-hundred and forty one articles were identified and screened, of which 26 met the eligibility criteria and were selected. Seven of them were non-systematic reviews that described two or more HTA organizations. Ten studies were focused on the advice offered by individual organizations, and eight described the EMA and EUnetHTA parallel or joint advice. We found variations in the technology assessed, services offered, stage of development and costs for advisory services. Conclusions: Early and scientific advice would help manufacturers focus their product development on what is needed for the management of specific diseases. Most of the examples or services found refer to drugs as well as to some medical devices and diagnostics. A common definition of the type of advice that could be offered for different health technologies by HTA bodies to ascertain health care systems and manufacturers' needs, in addition to the timeline in which that advice needs to be given, would help HTA bodies provide the right support at the right time. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020219401, PROSPERO CRD42020219401.

An evidence-based framework for identifying technologies of no or low-added value (NLVT).

OBJECTIVE: To synthetize the state of the art of methods for identifying candidate technologies for disinvestment and propose an evidence-based framework for executing this task. METHODS: An interpretative review was conducted. A systematic literature search was performed to identify secondary or tertiary research related to disinvestment initiatives and/or any type of research that specifically described one or more methods for identifying potential candidates technologies, services, or practices for disinvestment. An iterative and critical analysis of the methods described alongside the disinvestment initiatives was performed. RESULTS: Seventeen systematic reviews on disinvestment or related terms (health technology reassessment or medical reversal) were retrieved and methods of 45 disinvestment initiatives were compared. On the basis of this evidence, we proposed a new framework for identifying these technologies based on the wide definition of evidence provided by Lomas et al. The framework comprises seven basic approaches, eleven triggers and thirteen methods for applying these triggers, which were grouped in embedded and ad hoc methods. CONCLUSIONS: Although identification methods have been described in the literature and tested in different contexts, the proliferation of terms and concepts used to describe this process creates considerable confusion. The proposed framework is a rigorous and flexible tool that could guide the implementation of strategies for identifying potential candidates for disinvestment.

Variability in the prescription of drugs with uncertain effectiveness. The case of SYSADOA in the Basque Country.

Background: The majority of clinical practice guidelines do not recommend the use of SYSADOA (Symptomatic Slow Action Drugs for Osteoarthritis) for the treatment of osteoarthritis because of the lack of evidence or uncertainty around their efficacy. Nevertheless, the Spanish Public Health Service continues funding these drugs. Aim: The aim of this study is to describe the prescription status of SYSADOA in the primary care units of the Basque Country during 2011; to determine if variability exists among them; and to examine if the variability could be explained by the health care region each PC unit belongs to. Methods: Prescription data for SYSADOA during 2011 was obtained from the Basque Ministry for Health. In the Basque Country, primary care is divided into seven regions, each region consisting of several primary care units, which were used as the unit of analysis. Defined daily doses (DDD) per 1,000 inhabitant-days (DHD) were calculated. Data were standardized by sex and age using the total population of the Basque Country as the reference population. Small area statistics were calculated (extremal quotient, coefficient of variation and systematic component of variation). The influence of the region to which primary care units belonged was also analysed. R software (version R-2.15.0) was used for the analysis. Results: SYSADOA prescription during 2011 accounted for an expense of 4.5 million euros for the Basque Health Service. The crude rate of consumption of SYSADOA was 7.81 DDD per 1,000 inhabitant-days. The obtained external quotient was 13.67. The prescription of SYSADOA of the primary care units located in the 95th percentile was six times higher than the ones located in the 5th percentile. The region to which units belonged accounted for 57% of the observed variability. Discussion: The uncertainty around these drugs could be reflected in the existing variability of their prescription level. The analysis of the variability in the prescription of drugs with no demonstrated efficacy could help in allocating resources into other services or health technologies supported by evidence, thereby contributing to the improvement of health outcomes.

Methodological systematic review identifies major limitations in prioritization processes for updating.

OBJECTIVES: The aim of the study was to identify and describe strategies to prioritize the updating of systematic reviews (SRs), health technology assessments (HTAs), or clinical guidelines (CGs). STUDY DESIGN AND SETTING: We conducted an SR of studies describing one or more methods to prioritize SRs, HTAs, or CGs for updating. We searched MEDLINE (PubMed, from 1966 to August 2016) and The Cochrane Methodology Register (The Cochrane Library, Issue 8 2016). We hand searched abstract books, reviewed reference lists, and contacted experts. Two reviewers independently screened the references and extracted data. RESULTS: We included 14 studies. Six studies were classified as descriptive (6 of 14, 42.9%) and eight as implementation studies (8 of 14, 57.1%). Six studies reported an updating strategy (6 of 14, 42.9%), six a prioritization process (6 of 14, 42.9%), and two a prioritization criterion (2 of 14, 14.2%). Eight studies focused on SRs (8 of 14, 57.1%), six studies focused on CGs (6 of 14, 42.9%), and none were about HTAs. We identified 76 prioritization criteria that can be applied when prioritizing documents for updating. The most frequently cited criteria were as follows: available evidence (19 of 76, 25.0%), clinical relevance (10 of 76; 13.2%), and users' interest (10 of 76; 13.2%). CONCLUSION: There is wide variability and suboptimal reporting of the methods used to develop and implement processes to prioritize updating of SRs, HTAs, and CGs.

Post-introduction observation of healthcare technologies after coverage: the Spanish proposal.

OBJECTIVES: When a new health technology has been approved by a health system, it is difficult to guarantee that it is going to be efficiently adopted, adequately used, and that effectiveness, safety, and consumption of resources and costs are in line with what was expected in preliminary investigations. Many governmental institutions promote the idea that efficient mechanisms should be established aimed at developing and incorporating continuous evidence into health technologies management. The purpose of this article is to stimulate the discussion on systematic post-introduction observation of health technologies. METHODS: Literature review and input of HTA experts. RESULTS: The study addresses the key issues related to post-introduction observation and presents a summary of the guide commissioned by the Spanish Ministry of Health, Social Policy and Equality to the Galician HTA agency for the prioritization and implementation of systematic post-introduction observation in Spain. The manuscript describes the prioritization tool developed as part of this project and discusses the main aspects of protocol development, observation implementation, and assessment of results. CONCLUSIONS: The observation of prioritized health technologies after they are introduced in standard clinical practice can provide useful information for health organizations. However, implementing the observation of health technologies can require specific policy frameworks, commitment from different stakeholders, and dedicated funding.

Post-marketing health technology monitoring. The analysis of an experience from a clinical perspective.

INTRODUCTION: A system for monitoring the use of aphaeresis in the treatment of ulcerative colitis (UC), named system for monitoring aphaeresis in ulcerative colitis (SiMAC), was designed in 2006 in the Basque Country. In the present study, the opinion of the clinicians who participated in SiMAC was evaluated, in order to identify the barriers and gather suggestions that could improve implementation of this kind of system. METHODS: A mixed questionnaire was designed, in order to gather clinicians' assessments of the SiMAC monitoring system. RESULTS: The response rate was 73.9% (17/23). The data from 40.96% (159/388) of patients with UC treated with aphaeresis was recorded. The main reasons for not including the data from all treated patients were a lack of required data or not meeting the study inclusion criteria. Positive aspects of the SiMAC were identified, as the simplicity of data collection and its systematic, multi-center approach. The negative aspects mentioned were the use of a local computer application and the lack of time for health professionals to enter data. DISCUSSION: The use of monitoring systems helps to formalize the introduction of technologies of little-known effectiveness; involve clinicians and medical societies in coming to agreement and obtaining information about the safety, effectiveness or efficiency of new technologies; and provide relevant information to healthcare administrations for making decisions about the introduction of new technologies into healthcare practice. In order for a monitoring system to work, the process must be straightforward. A minimum set of key variables that are easy to collect must be selected, and an effort made to involve a range of stakeholders, especially institutions and scientific societies, to support the work group.

Guiding the process of health technology disinvestment.

OBJECTIVES: To develop a guideline for health technology disinvestment. METHODS: The Nominal Group Technique was used to determine relevant aspects of disinvestment decision-making. Ideas reaching consensus and previous Spanish guidelines on the acquisition of new health technologies (GANT) and new genetic tests (GEN) structures were used to develop the domains and contents of GuNFT (Guideline for Not Funding Health Technologies). The draft was peer reviewed by local and international experts and their suggestions were incorporated to the first GuNFT version. RESULTS: Thirty-five ideas reached consensus. The most relevant ones referred to the reasons for disinvesting in a technology and the key aspects that would facilitate disinvestment acceptance. Considering both consensus ideas and GANT and GEN guidelines, the first GuNFT draft was elaborated. After the review process, section numbers and contents were changed. The resulting GuNFT guideline was finally divided into six domains related to: (1) general preliminary recommendations, (2) completing the application form, (3) checking and prioritising applications, (4) assessment, (5) final decision and (6) action plan design. A software was also developed to facilitate GuNFT implementation. CONCLUSIONS: Disinvestment should be a guided process. Accordingly, we present the first guideline for that purpose.

The GRADE approach for assessing new technologies as applied to apheresis devices in ulcerative colitis.

BACKGROUND: In the last few years, a new non-pharmacological treatment, termed apheresis, has been developed to lessen the burden of ulcerative colitis (UC). Several methods can be used to establish treatment recommendations, but over the last decade an informal collaboration group of guideline developers, methodologists, and clinicians has developed a more sensible and transparent approach known as the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). GRADE has mainly been used in clinical practice guidelines and systematic reviews. The aim of the present study is to describe the use of this approach in the development of recommendations for a new health technology, and to analyse the strengths, weaknesses, opportunities, and threats found when doing so. METHODS: A systematic review of the use of apheresis for UC treatment was performed in June 2004 and updated in May 2008. Two related clinical questions were selected, the outcomes of interest defined, and the quality of the evidence assessed. Finally, the overall quality of each question was taken into account to formulate recommendations following the GRADE approach. To evaluate this experience, a SWOT (strengths, weaknesses, opportunities and threats) analysis was performed to enable a comparison with our previous experience with the SIGN (Scottish Intercollegiate Guidelines Network) method. RESULTS: Application of the GRADE approach allowed recommendations to be formulated and the method to be clarified and made more explicit and transparent. Two weak recommendations were proposed to answer to the formulated questions. Some challenges, such as the limited number of studies found for the new technology and the difficulties encountered when searching for the results for the selected outcomes, none of which are specific to GRADE, were identified. GRADE was considered to be a more time-consuming method, although it has the advantage of taking into account patient values when defining and grading the relevant outcomes, thereby avoiding any influence from literature precedents, which could be considered to be a strength of this method. CONCLUSIONS: The GRADE approach could be appropriate for making the recommendation development process for Health Technology Assessment (HTA) reports more explicit, especially with regard to new technologies.

Scanning the horizon of obsolete technologies: possible sources for their identification.

OBJECTIVES: The aim of this study was to identify and rank the sources for the detection of potentially obsolete technologies (POTs). METHODS: A specific questionnaire related to the search strategies and sources used for the identification of POTs and also for ineffective, inefficient or harmful health technologies was sent to the Health Technology Assessment International's Information Resources Group (HTAi-IRG) group. With the obtained information and taking into account the sources used for the identification of new and emerging technologies, a second questionnaire was elaborated and sent to EuroScan and International Network of Agencies for Health Technology Assessment (INAHTA) members, who had to select and score them. For the final ranking, the number of votes and the median score were taken into account. RESULTS: Seven HTAi-IRG members answered to the first questionnaire. Seventeen agencies answered to the second one (thirteen EuroScan members and four more members from INAHTA), but only seven had worked in the identification of POTs and one of them using only experts for it. The remaining six agencies answered the part related to devices, diagnostics, and procedures; five of them did it for settings and programmes and only three for drugs. The Canadian Agency for Drugs and Technologies in Health (5 votes; median = 2), Cochrane Collaboration (5 votes; median = 3), NICE (4 votes; median = 1), Food and Drug Administration (4 votes; median = 1.5), and EuroScan (4 votes, median = 2) were the most relevant sources for devices and diagnostics. CONCLUSIONS: There is little experience on POTs identification. The identified sources provide mostly indirect information and further research should take place to determine the best use of them.

Differences in the identification process for new and emerging health technologies: analysis of the EuroScan database.

OBJECTIVES: The aim of this study was to analyze the EuroScan Database and to describe and compare the characteristics of the included technologies and participating agencies. METHODS: Data of interest were exported from the EuroScan Database to Excel and to SPSS. A descriptive analysis depending on the agency, type of technology, stage of diffusion, and technology purpose was conducted. A frequency distribution analysis of the diffusion stage for different technology types and assigned purposes was made with the EpiCalc 2000 statistical calculator. A p value of less than .05 was considered to be statistically significant. RESULTS: Four agencies introduced the great majority of the technologies (81 percent), with drugs representing the 46.26 percent of the total, followed by devices (21.21 percent). The purpose of 24.45 percent of the identified technologies was not specified, and 34.58 percent of them were identified at the investigational or phase III stage. The frequency distribution of diffusion stage at identification was found to be similar for devices and diagnostics (p = .543), whereas drugs were identified earlier than devices (p <.001). Some agencies were found to focus their work on drugs, whereas others focused mainly on devices. Interagency differences were also observed with regard to the stage of diffusion at which technologies were identified. CONCLUSIONS: This is the first analysis of one of the most important databases on new and emerging health technologies. Our study suggests that more active strategies should be designed to provide an earlier identification, mainly in the case of devices.