Iñaki Gutiérrez-Ibarluzea

Personalizing health care: feasibility and future implications.

Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer’s perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.

Dabigatran - a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs

Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use. Objective: To (i) review authority activities in over 30 countries and regions, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications for all major stakeholder groups. Methodology: Descriptive review and appraisal of activities regarding dabigatran and the development of guidance for groups through an iterative process. Results: There has been a plethora of activities among authorities to manage the prescribing of dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions, and monitoring of prescribing post-launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.

Guiding the process of health technology disinvestment

OBJECTIVESnTo develop a guideline for health technology disinvestment.nnnMETHODSnThe 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.nnnRESULTSnThirty-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.nnnCONCLUSIONSnDisinvestment should be a guided process. Accordingly, we present the first guideline for that purpose.

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

OBJECTIVESnThe aim of this study was to identify and rank the sources for the detection of potentially obsolete technologies (POTs).nnnMETHODSnA 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 Internationals 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.nnnRESULTSnSeven 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.nnnCONCLUSIONSnThere 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.

Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs.

Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. Objective: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities. Methodology: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies. Results: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.

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

BackgroundIn 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.MethodsA 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.ResultsApplication 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.ConclusionsThe 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.

Policies of screening for colorectal cancer in European countries

OBJECTIVESnThe aim of this study was to analyze the current status of population screening for colon/rectum cancer in Europe to compare the different strategies, the coverage, the existence of pilot experiences, regional coverages, and the risk factors considered in each strategy.nnnMETHODSnA comprehensive, systematic search was performed in the literature for documents addressing population screening for colon/rectum cancer in Europe. An ad hoc questionnaire was prepared including questions considered relevant. The questionnaire was reviewed by experts in the area. To identify key informants, colleague members of the International Network of Agencies for Health Technology Assessment (INAHTA), participants in the EUnetHTA project, or representatives of the ministries of health of the different European countries were contacted. The information provided by key informants was checked with information directly obtained from the ministries of health, gray literature, and research documents.nnnRESULTSnAn 88 percent response rate was obtained. In countries for which no questionnaire data were collected, information was directly retrieved from the Web sites of the corresponding ministries. Four countries were found to perform population screenings: Austria, France, Germany, and the United Kingdom. However, they used different strategies. Five countries had begun regional or local strategies: Denmark, Finland, Italy, Spain, and Switzerland, and two additional countries (the Netherlands and Norway) reported ongoing research studies intended to determine the best strategy to implement a population-based screening program. Differences were found in age range, procedure chosen, and follow-up period.nnnCONCLUSIONSnEven though the European Council recommended a wider implementation of population screening for colon/rectum cancer, our results suggest that this recommendation continues to be valid. The differences found in screening strategies (in terms of age range, procedures, risk factors considered, and follow-up periods) are not warranted by the results obtained in research studies or regional-national cancer registries.

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

OBJECTIVESnThe aim of this study was to analyze the EuroScan Database and to describe and compare the characteristics of the included technologies and participating agencies.nnnMETHODSnData 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.nnnRESULTSnFour 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.nnnCONCLUSIONSnThis 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.

Addressing issues in health technology assessment promotion: Motives, enablers, and barriers.

OBJECTIVESnThe aim of this study was to analyze the motives, enablers, and barriers to promote or initiate health technology assessment (HTA) in different contexts.nnnMETHODSnAn observational study design was used to address the above question that included a survey questionnaire and a two-phase study. The respondents for the questionnaire and first round of the study were from HTA agencies of high income countries and those low and middle income countries that have managed to establish HTA agencies (n = 50), that are members of International Network of Agencies for Health Technology Assessment (INAHTA), EuroScan, or European network for Health Technology Assessment (EUnetHTA). The second round of the study was exclusively with respondents from low and middle income countries that were manly affiliated to Health Technology Assessment International (HTAi) interest subgroup for low and middle income countries and aimed to initiate HTA activities (n = 34).nnnRESULTSnForty-one of fifty HTA agencies answered the survey questionnaire. Thirty-three of fifty individuals belonging to HTA agencies from high income countries and sixteen of thirty-four individuals from low and middle income countries answered in the first and second phases of the study, respectively. In the promotion and/or initiation of HTA, the top three motives were the same for both high income and low and middle income countries. The top three enablers were also similar but the prioritization varies. The top three barriers were more context specific.nnnCONCLUSIONSnHTA promotion or initiation is influenced by the following: (i) key players that affect the time taken to establish HTA agencies; (ii) three models for HTA promotion and initiation: top-down (political interest), bottom-up (academic/research interest), and converging (political and academic/research interests); and (iii) motives, enablers, and barriers at the local context.

Health technology performance assessment : real-world evidence for public healthcare sustainability

OBJECTIVESnHealth technology financing is often based on randomized controlled trials (RCTs), which are often the same ones used for licensing. Because they are designed to show the best possible results, typically Phase III studies are conducted under ideal and highly controlled conditions. Consequently, it is not surprising that technologies do not always perform in real life in the same way as controlled conditions. Because financing (and price paid) decisions can be made with overestimated results, health authorities need to ask whether health systems achieve the results they expect when they choose to pay for a technology. The optimal way to answer this question is to assess the performance of financed technologies in real-world settings. Health technology performance assessment (HTpA) refers to the systematic evaluation of the properties, effects, and/or impact of a health intervention or health technology in the real world to provide information for investment/disinvestment decisions and clinical guideline updates. The objective is to describe the development and principal aspects of the Guideline for HTpA commissioned by the Brazilian Ministry of Health.nnnMETHODSnOur methods used include extensive literature review, refinement with experts across countries, and public consultation.nnnRESULTSnA comprehensive guideline was developed, which has been adopted by the Brazilian government.nnnCONCLUSIONnWe believe the guideline, with its particular focus on disinvestment, along with the creation of a specific program for HTpA, will allow the institutionalization and continuous improvement of the scientific methods to use real-world evidence to optimize available resources not only in Brazil but across countries.