In this issue of the Journal, Panteli et al. (6) provide insight into the extent to which a gender-sensitive approach is adopted by sixty health technology assessment (HTA) agencies worldwide. Their findings should make all of us involved in the production of HTA take pause: less than a handful of the agency Web sites that were examined by Panteli's team made any mention of gender as an explicit consideration in priority setting processes or in the HTA methods used (6). This is despite the fact that gender is recognized as a social determinant of health (1) and despite best practices that acknowledge the need to account for equity issues—of which gender is one—in the design, conduct, and reporting of HTA (3;4). Assuming we take the findings of Panteli et al. at face value, this does seem to be a case of “do as I say, not as I do.”

Objectives: To explore the cost-effectiveness of early biologic treatment, followed by dose-reduction in the case of remission, of active rheumatoid arthritis (RA), compared with standard treatment with methotrexate (MTX) in Sweden.

Methods: Effectiveness (function, disease activity, erosions) in early RA for both alternatives was taken from a clinical trial comparing etanercept (ETA) combined with MTX to MTX alone. Patients discontinuing treatment can switch to another or their first biologic treatment. For patients in remission (Disease Activity Score [DAS28] < 2.6), ETA is reduced to half the dose. Return to full dose occurs when DAS28 reaches ≥ 3.2 again. Costs and utilities by level of functional capacity from an observational study are used. The model is analyzed as a micro-simulation and results are presented from the societal perspective for Sweden, for 10 years; costs (€2008) and effects are discounted at 3 percent. Sensitivity analysis was performed for the perspective, the time horizon, switching, and dose-reduction.

Results: The main analysis conservatively assumes 50 percent switching at discontinuation. The cost per quality-adjusted life-year (QALY) gained with early ETA/MTX treatment is €13,500 (societal perspective, incremental cost of €15,500 and incremental QALYs of 1.15). With 75 percent switching, the cost per QALY gained was €10,400. Over 20 years, the cost per QALY gained was €8,200. Results were further sensitive to the time patients remained on half dose and the perspective.

Conclusions and Policy Implications: This study combines clinical trial and clinical practice data to explore cost-effective treatment scenarios in early RA, including the use of biologics. Our results indicate that a situation where a considerable proportion of patients achieve remission, dose-adjustments will increase the cost-effectiveness of treatment.

Background: We calculated the daily cost of implantable cardioverter-defibrillators (ICDs) based on their actual longevity to prove whether the up-front cost is a reliable parameter for the ICD purchasing-process.

Methods. Longevity of single chamber (SC), double chamber (DC), and biventricular (BiV) ICDs from Medtronic (MDT), Guidant (GDT), and St. Jude Medical (SJM) was measured in all the patients implanted in years 2000, 2001, 2002 who reached device replacement within December 31, 2009. The cost of each ICD (device + lead/s) was normalized for its own longevity. Data are expressed as median (25th–75th percentile).

Results: A total of 123/153 patients completed the study, 70 percent being alive 8 years after implantation. MDT devices had a superior longevity compared with GDT and SJM (p < .001). Fifty-eight percent of replaced ICDs had a service life at least 1 year shorter than the manufacturers' prediction. Longer-lasting devices had a significantly lower daily cost: €4.8 (4.6–5.7) versus €6.8 (6.2–9.2) and €6.9 (6.2–7.6) for SC (p < .001); €6.9 (6.8–7.7) versus €12.6 (11.8–13.3) and €13.4 (10.3–16.1) for DC; €8.5 (8.3–10.3) versus €15.4 (15.1–15.8) and €14.6 (14.1–14.9) for BiV (p < .005).

Conclusions: The true cost of ICD treatment is strictly dependent on device longevity, whereas device up-front cost is unreliable. This aspect should be valued in the technology purchasing process, and could set the basis for an outcome-based reimbursement system. Our observations may be the benchmark respectively for ICD longevity and daily ICD cost in future comparisons. Independent observations in the real-life scenario are needed to properly value newer technologic improvements.

Objectives: In clinical trials of new cancer drugs, reliable data for progression-free survival will often become available far sooner than reliable data for overall survival. The aim of this study was to determine how many months it would be expected that any given new drug for metastatic breast or colorectal cancer will add to overall survival times given that the number of months the drug adds to progression-free survival times relative to a standard drug is roughly already known.

Methods: A literature search was conducted over Medline for randomized controlled trials (RCTs) published between January 1980 and August 2008 that assessed the effect of a drug treatment in comparison to an alternative drug treatment on patients with either metastatic breast or metastatic colorectal cancer.

Results: The literature search found 95 and 74 RCTs for metastatic breast and colorectal cancer, respectively, that satisfied the study's inclusion criteria. The results from these trials are consistent, in the case of each of these two metastatic cancers, with gains in time to disease progression being generally associated with no gains or with very slight gains or losses in post-progression survival (i.e., the time between disease progression and death).

Conclusions: It would appear that drugs for metastatic breast or colorectal cancer that extend, by a given amount, the time period between the start of treatment and disease progression (i.e., time to progression) have a strong tendency to extend, by roughly the same amount, the period between the start of treatment and death (i.e., overall survival).

Objectives: Extended-release therapies avoid the need for children with attention-deficit/hyperactivity disorder (ADHD) to take medication at school. Recently a transdermal delivery system has been developed which can allow symptom control all day long but with greater dosing flexibility. This study explored the parents' preferences regarding oral and transdermal therapy.

Methods: A nonsystematic and qualitative literature review and in-depth interviews with parents and physicians helped identify salient treatment attributes for a discrete choice experiment. Treatment attributes included mode of administration (tablet or transdermal), speed of onset (30–90 min); duration (lasts until 3–9 pm) and ability to tailor the drug to different needs (no flexibility, limited flexibility, easy to adjust to different days). A convenience sample of parents of children treated for ADHD (n = 200) were recruited using a recruitment agency. Data were analyzed using generalized estimating equations (GEE).

Results: Parents' preferred once-a-day oral therapy (odds ratio [OR] = 1.76 [95 percent confidence interval {CI}, 1.43 – 2.18]); rapid speed of onset (OR = 1.22 [95 percent CI, 1.07 – 1.39]), and symptom control until 9 pm (OR = 3.79 [95 percent CI, 2.98 – 4.82]). Analyses identified that 30 percent of parents preferred transdermal treatment and this subgroup preferred treatments with a fast onset of action.

Conclusions: This survey demonstrates that parents of ADHD children have different preferences for the ADHD treatments prescribed for their children. A distinct subgroup of parents prefer the transdermal therapy. These parents were less likely to be working and so monitoring compliance and doing after school activities may have been easier.

Objectives: Gender as a social construct is a recognized health determinant. Because best practice in reporting health technology assessment (HTA) clearly specifies the need to appraise a technology's social impact within the target population, the extent to which gender issues are taken into account in HTA production is of interest, not only in light of equitable practices but also for reasons of effectiveness. The aim of this study is to provide a first assessment of the degree of gender sensitivity shown by HTA agencies around the world today.

Methods: The Web sites of sixty HTA agencies were analyzed. The consideration of gender aspects was specifically looked for in each agency's general mission statement, its priority setting process, and its methodological approach. Additionally, specific gender-oriented initiatives not belonging to any of the aforementioned categories were identified.

Results: Of the sixty agencies, less than half mention a commitment to addressing the social implication of health technologies. Only fifteen institutions make information on their priority setting principles available on their Web sites and gender was an issue in two of those cases. Data on methodology were obtainable online from18 agencies, two of which mentioned gender issues explicitly. Finally, gender-oriented initiatives were identified by thirteen agencies.

Conclusions: A gender-sensitive approach is apparently rarely adopted in current HTA production. Exceptional practices and relevant tools do exist and could serve as examples to be promoted by international collaborative networks.

Objectives: Values are intrinsic to the use of health technology assessments (HTAs) in health policy, but neglecting value assumptions in HTA makes their results appear more robust or normatively neutral than may be the case. Results of a 2003 survey by the International Network of Agencies for Health Technology Assessment (INAHTA) revealed the existence of disparate methods for making values and ethical issues explicit when conducting HTA.

Methods: An Ethics Working Group, with representation from sixteen agencies, was established to develop a framework for addressing ethical issues in HTA. Using an iterative approach, with email exchanges and face-to-face workshops, a report on Handling Ethical Issues was produced.

Results: This study describes the development process and the agreed upon framework for reflexive ethical analysis that aims to uncover and explore the ethical implications of technologies through an integrated, context-sensitive approach and situates the proposed framework within previous work in the development of ethics analysis in HTA.

Conclusions: It is important that methodological approaches to address ethical reflection in HTA be integrative and context sensitive. The question-based approach described and recommended here is meant to elicit this type of reflection in a way that can be used by HTA agencies. The questions proposed are considered only as a starting point for handling ethics issues, but their use would represent a significant improvement over much of the existing practice.

Objectives: To propose a new method for comparing and integrating original qualitative data with systematic reviews of quantitative and qualitative studies, demonstrated by a study of the psychosocial needs of chronic fatigue syndrome (CFS) sufferers in Québec.

Methods: A systematic literature review was performed across various databases for English and French language studies, on the psychosocial aspects of CFS. Qualitative, quantitative, and mixed method studies published between January 1994 and July 2008 were included. Unpublished literature and reference lists of included studies were also searched. Themes identified in the literature were used to guide semi-structured interviews with seventeen CFS-sufferers, mostly recruited from a large specialist practice in Montreal. Interviews were transcribed verbatim and validated by a research assistant. Transcripts were coded using the identified themes. New codes were created when new issues arose. All themes were subsequently synthesized into overall categories using a constant comparative method.

Results: The literature search yielded thirty-one papers: twenty-eight primary studies and three systematic reviews. Twelve themes were identified and synthesized into four overall problem categories, such as “Lack of professional recognition.” Interviews confirmed findings from the literature, but also revealed unidentified needs specific to CFS-sufferers in Québec. Policy recommendations were provided to address these needs.

Conclusions: Multi-Source Synthesis provides a systematic method for synthesizing data from original studies with literature findings, thereby broadening the knowledge base and the local relevance of decisions concerning specific patient populations.

Objectives: Evidence-based guideline committees are multidisciplinary and explicitly consider the existing evidence. They are thus in an ideal position to identify research gaps. However, gaps have not been systematically identified through guidelines. We pilot tested a method to systematically identify and classify gaps from evidence-based guidelines.

Methods: We reviewed all evidence-based guidelines published by the Cystic Fibrosis Foundation. We identified research gaps as topics for which there was insufficient evidence (recommendations were not made or consensus recommendations were made) and topics specified as needing further research. We characterized gaps using a standard framework and classified them by type of management issue, specificity of target population, and age of target population.

Results: We identified sixty-two research gaps in five guidelines (mean = 12.4/guidelines document). While thirteen gaps were topics specified as needing further research, most (n = 49) were topics with insufficient evidence. Of these forty-nine, recommendations were not made for twenty-two topics while consensus recommendations were made for twenty-seven topics. Most gaps were issues of comparative effectiveness (44/62), addressed the general cystic fibrosis population (40/62), and were specific to infants (33/62). Relevant comparisons and outcomes were explicitly stated for only 7 percent and 16 percent of gaps respectively.

Conclusions: Almost 80 percent of the gaps were not topics identified as future research needs in the guidelines documents but rather were topics with insufficient evidence for making recommendations. Although we used cystic fibrosis in the United States as an example, the method we developed could be applied in other settings, including other countries and for different diseases.

Background: The relationship between regulatory approval on the one hand and health technology assessment (HTA) and coverage on the other is receiving growing attention. Those responsible for regulatory approval, HTA, and coverage have different missions and their information requirements reflect these. There is nonetheless an increasingly popular view that improved communication and coordination between these functions could allow them all to be undertaken effectively with a lower overall burden of evidence requirements, thus speeding patient access to new products and reducing unnecessary barriers to innovation. This study summarizes the main points emerging from a recent discussion of this topic at the HTAi Policy Forum.

Results and Conclusions: After considering the roles of the various bodies, stakeholder perspectives and some current practical initiatives, those present at the Forum meeting discussed possible goals and challenges for improved interactions—in general and at specific stages of the product development life cycle. Opportunities for progress were seen in: continuing the dialogue to promote understanding and interaction between the different bodies and stakeholders; working to align scientific advice for manufacturers on the design and data requirements of pre- and post-marketing evaluation of products (specifically phase 2/3 and phase 4 trials for drugs); and extending the current dialogue to include discussion of product development to address unmet health needs.

Objectives: This article provides a detailed understanding of the differences in selected formulary submission guidelines supplied by various health technology assessment (HTA) agencies and indicates how these differences can impact the evidence base used to populate the HTA.

Methods: Detailed summaries of the recommended methods for evidence generation, organized by topic areas relevant for clinical and economic data, for twelve countries in Europe, North America, and Australia where HTA processes are well developed were prepared. Using these summaries, we provide examples of the likely impact these differences in recommended methods could have on the evidence base used to evaluate new health technologies.

Results: Areas where recommendations differed included methodologies for systematic literature reviews (e.g., preferred databases and study designs for inclusion); selection of appropriate comparators; guidance on critical appraisal and synthesis of clinical evidence; appropriate sources for health value measures, resource use, and cost data; and approaches to uncertainty analyses. Performing literature searches that capture all relevant studies and then creating subsets of the literature based on a listing of country-specific requirements could allow for direct comparison of the evidence bases associated with the different guidelines.

Conclusions: If the formulary submission guidelines were followed as written, different (although overlapping) bodies of evidence likely would be generated for each country, which could contribute to disparate assessments and recommendations. This comparison of the formulary submission guidelines could contribute to an understanding of why clinical and reimbursement decisions vary across countries.