Background: The Alberta Hip and Knee Replacement Project developed a new evidence-based clinical pathway (NCP) for total hip (THR) and knee (TKR) replacement. The aim was to facilitate the delivery of services in a timely and cost-effective manner while achieving the highest quality of care for the patient across the full continuum of care from patient referral to an orthopedic surgeon through surgery, recovery, and rehabilitation. The purpose of this article is to provide an overview of the study design, rationale, and execution of this project as a model for health technology assessment based on comparative effectiveness of alternative clinical pathways.

Methods: A pragmatic randomized controlled trial study design was used to evaluate the NCP compared with the standard of care (SOC) for these procedures. The pragmatic study design was selected as a rigorous approach to produce high quality evidence suitable for informing decisions between relevant interventions in real clinical practice. The NCP was evaluated in three of the nine regional health authorities (RHAs) in Alberta with dedicated central intake clinics offering multidisciplinary care teams, constituting 80 percent of THR and TKR surgeries performed annually in Alberta. Patients were identified in the offices of twenty orthopedic surgeons who routinely performed THR or TKR surgeries. Evaluation outcome measures were based on the six dimensions of the Alberta Quality Matrix for Health (AQMH): acceptability, accessibility, appropriateness, effectiveness, efficiency and safety. Data were collected prospectively through patient self-completed questionnaires at baseline and 3 and 12 months after surgery, ambulatory and inpatient chart reviews, and electronic administrative data.

Results: The trial design was successful in establishing similar groups for rigorous evaluation. Of the 4,985 patients invited to participate, 69 percent of patients consented. A total of 3,434 patients were randomized: 1,712 to SOC and 1,722 to the NCP. The baseline characteristics of patients in the two study arms, including demographics, comorbidity as measured by CDS and exposure to pain medications, and health-related quality of life, as measured by Western Ontario and McMaster Universities Osteoarthritis Index and Short Form-36, were similar.

Conclusions: The Alberta Hip and Knee Replacement Project demonstrates the feasibility and advantages of applying a pragmatic randomized controlled trial to ascertain comparative effectiveness. This is a model for health technology assessment that incorporates how clinical pathways can be effectively evaluated.

To reduce harm to the environment resulting from the production, use, and disposal of health technologies, there are different options for how health technology assessment (HTA) agencies can consider environmental information. We identified four approaches that HTA agencies can use to take environmental information into account in healthcare decision making and the challenges associated with each approach. Republishing data that is in the public domain or has been submitted to an HTA agency we term the “information conduit” approach. Analyzing and presenting environmental data separately from established health economic analyses is described as “parallel evaluation.” Integrating environmental impact into HTAs by identifying or creating new methods that allow clinical, financial, and environmental information to be combined in a single quantitative analysis is “integrated evaluation.” Finally, evidence synthesis and analysis of health technologies that are not expected to improve health-related outcomes but claim to have relative environmental benefits are termed “environment-focused evaluation.”

Objectives: The European Code Against Cancer recommends individuals aged ≥50 should participate in colorectal cancer screening. CT-colonography (CTC) is one of several screening tests available. We systematically reviewed evidence on, and identified key factors influencing, cost-effectiveness of CTC screening.

Methods: PubMed, Medline, and the Cochrane library were searched for cost-effectiveness or cost-utility analyses of CTC-based screening, published in English, January 1999 to July 2010. Data was abstracted on setting, model type and horizon, screening scenario(s), comparator(s), participants, uptake, CTC performance and cost, effectiveness, ICERs, and whether extra-colonic findings and medical complications were considered.

Results: Sixteen studies were identified from the United States (n = 11), Canada (n = 2), and France, Italy, and the United Kingdom (1 each). Markov state-transition (n = 14) or microsimulation (n = 2) models were used. Eleven considered direct medical costs only; five included indirect costs. Fourteen compared CTC with no screening; fourteen compared CTC with colonoscopy-based screening; fewer compared CTC with sigmoidoscopy (8) or fecal tests (4). Outcomes assessed were life-years gained/saved (13), QALYs (2), or both (1). Three considered extra-colonic findings; seven considered complications. CTC appeared cost-effective versus no screening and, in general, flexible sigmoidoscopy and fecal occult blood testing. Results were mixed comparing CTC to colonoscopy. Parameters most influencing cost-effectiveness included: CTC costs, screening uptake, threshold for polyp referral, and extra-colonic findings.

Conclusion: Evidence on cost-effectiveness of CTC screening is heterogeneous, due largely to between-study differences in comparators and parameter values. Future studies should: compare CTC with currently favored tests, especially fecal immunochemical tests; consider extra-colonic findings; and conduct comprehensive sensitivity analyses.

Objective: The objective of this paper is to determine prevalence and characteristics of acute care for elders (ACE) units and hospital characteristics associated with the presence of an ACE unit.

Methods: Data on characteristics and prevalence of ACE units were obtained by surveying all established geriatric medical divisions across U.S. medical schools. Data on hospital characteristics such as number of beds, revenue, number of Medicare inpatients, and average length of stay were obtained from the 1999 American Hospital Association Annual Survey Data. Descriptive statistics and t test were used to analyze the characteristics of ACE units. Stepwise logistic regression was used to analyze the hospital characteristics associated with the presence of an ACE unit.

Results: The survey identified 16 geriatric divisions and programs with ACE units. Hospitals that have ACE units differ significantly with respect to number of beds and total revenue, compared with institutions that do not have an ACE unit. Stepwise logistic regression indicated total hospital revenue was the only factor significantly associated with the presence of an ACE unit.

Conclusions: ACE units are attractive interdisciplinary models to address the particular needs of the elderly during their hospital stay. Low presence of ACE units warrants further research as to reasons more hospitals have not included them, given the available evidence for clinical, functional, and economic benefits.

Total treatment costs by stage at diagnosis are estimated for a sample of breast cancer patients. At 4 years, stage 4 cancers emerge as being more expensive to treat than those at earlier stages, although this difference fails to achieve significance when expected lifetime costs are considered. The inclusion of treatment cost estimates in a screening model indicates that screening may increase expected treatment costs by a marginal amount, although the model also suggests that the cost effectiveness ratio of breast cancer screening might be better than had originally been thought.

Objectives: The aim of this study was to obtain information on rapid health technology assessments (HTAs) prepared by members of the International Network of Agencies for Health Technology Assessment (INAHTA).

Methods: A questionnaire was prepared, drawing on earlier INAHTA documents for recording HTA impact. A request for responses was sent to member agencies, seeking information on rapid HTA reports prepared during 2006.

Results: Responses were provided on fifteen rapid HTAs, which covered both new and widely distributed technologies. The most common purpose for the HTAs (n = 8) was to inform coverage decisions, but other reasons included capital funding, formulary decisions, referral for treatment, program operation, guideline formulation, influence on routine practice, and indications for further research. All the rapid HTAs were considered by the agencies to have had some influence. The most common indications of influence were consideration by the decision maker, use of the HTA as reference material (both n = 10), and acceptance of recommendations or conclusions (n = 8).

Conclusions: Rapid HTAs are used for a broad range of technologies, to inform several types of decision, and are effective in informing the decision-making process. Supplementation of their findings by further assessments will be appropriate in some cases.

Background: Two general alternative approaches, cost-effectiveness analysis and the therapeutic added value approach, link the pricing and approval of drugs to value. Value as assessed by payers is a function of: benefit less cost, willingness to pay for benefit, and how they handle uncertainty.

Methods: This study uses international examples to explore the elements of value that can be included in the assessment of health technologies, approaches to scoring the elements of value and how they can be combined to make a decision.

Results: A range of value elements, measures, and approaches to aggregation are identified across different HTA systems. We show that seemingly arbitrary differences in measurement and aggregation can lead to significantly different outcomes, and argue that the choice of values, measures, and decision-making processes should be informed by the societal values that underpin a health system.

Conclusions: We identify three areas for further research to improve both health system and industry R&D decision making: (i) whether more consistency could be achieved across health systems on the elements of value that matter; (ii) the relative merits of discrete versus continuous measures of value; and (iii) how structured decision making (to aggregate the elements of value) could or should become.

The utility weights that are used in published scientific articles for assessing benefits in terms of quality adjusted life-years gained often have a weak theoretical and empirical basis. To a large extent, the weights seem to be used without critical thought and sensible discussion. In a majority of cases, the sensitivity of the results to the weights that have been chosen is not demonstrated, and readers are not provided with information in a way that facilitates independent calculations. This paper calls for a standard for future publications.

The principle that infants can be protected from invasive diseases caused by encapsulated organisms has been proved with the introduction of Haemophilus influenzae type b conjugate vaccines. The use of glycoconjugates to implement some of the goals of the Children's Vaccine Initiative requires a clear delineation of the chemical and immunological specifications for optimal vaccines.

Objectives: The aim of the study is to make an international comparison of Health Technology Assessment (HTA) Agencies, to show their similarities and differences.

Methods: An e-mail questionnaire was sent to thirty HTA agencies internationally. Questions related to the structure of the agency, the relationship with health-related institutions, the prescriptiveness of the decisions taken, the main core and the modalities to spread the assessment, and the type of funding.

Results: Twenty-four HTA Agencies answered the questionnaire: 25 percent in America, 4.2 percent in Australia, and 70.8 percent in Europe. Fifty-four percent of HTA Agencies are governmental institutions (83.3 percent have central government funding), while 62.5 percent have relationships with health-related governmental institutions. Of the agencies, 87 percent reported that their decisions are not prescriptive, while for 20.8 percent and 8.3 percent of them stated that this was the case totally or partially, respectively, especially for the governmental and American Agencies. Seventeen agencies (70.8 percent) declared their work on multiannual programs (77 percent of the governmental HTA Agencies and 100 percent of the American ones). The assessments mainly addressed diagnostic procedures (85.7 percent) and pharmaceuticals (25 percent). The most common way to disseminate results is by means of paper report (91.7 percent), followed by the Internet (16.7 percent), and seminars to expert audiences (12.5 percent).

Conclusions: The comparative analysis of HTA Agencies showed that governmental and American Agencies have a profound impact on the prescriptiveness of their assessment, and this could be linked to the fact that these types of Agencies work on multiannual programs. European and American HTA Agencies have many similarities in terms of type of assessment, funding, and dissemination of results.

Background: Information retrieval (IR) in health technology assessment (HTA) calls for transparency and reproducibility, but common practice in the documentation and presentation of this process is inadequate in fulfilling this demand.

Objectives: Our objective is to promote good IR practice by presenting the conceptualization of retrieval and transcription readable to non-information specialists, and reporting of effectively processed search strategies.

Methods: We performed a comprehensive database search (04/2010) to synthesize the current state-of-the-art. We then developed graphical and tabular presentation methods and tested their feasibility on existing research questions and defined recommendations.

Results: No generally accepted standard of reporting of IR in HTA exists. We, therefore, developed templates for presenting the retrieval conceptualization, database selection, and additional hand-searching as well as for presenting search histories of complex and lengthy search strategies. No single template fits all conceptualizations, but some can be applied to most processes. Database interface providers report queries as entered, not as they are actually processed. In PubMed®, the huge difference between entered and processed query is shown in “Details.” Quality control and evaluation of search strategies using a validated tool such as the PRESS checklist is suboptimal when only entry-query based search histories are applied.

Conclusions: Moving toward an internationally accepted IR reporting standard calls for advances in common reporting practices. Comprehensive, process-based reporting and presentation would make IR more understandable to others than information specialists and facilitate quality control.

The issue of evidence for decision-making, including formal policy-making and public health policy, has increased rapidly in prominence during the past few years. The term “evidence-based” was first used in health care in 1992, when Sackett and others coined the term “evidence-based medicine” (42). More recently, many have asked if public health activities are based on evidence (2;8;13;19;30).

Clinical practice guidelines are expanding their scope of authority from clinical decision making to collective policy making, and promise to gain ground as resource allocation tools in coming years. A close examination of how guidelines approach patient selection criteria offers insight into their ethical implications when used as resource allocation or rationing instruments. The purposes of this paper are: a) to examine the structure of allocative reasoning found in clinical guidelines; b) to identify the ethical principles implied and compare how guidelines enact these principles with how explicit systems-level rationing exercises and health policy analyses have approached them; and c) to offer some preliminary suggestions for how these ethical issues might be addressed in the process of guideline development. The resulting framework can be used by guideline developers and users to understand and address some of the ethical issues raised by guidelines for the use of scarce technologies.

Objectives: Evaluating the impact of recommendations based upon health technology assessment (HTA) represents a challenge for both HTA agencies and healthcare policy makers. This research sought to understand factors affecting the uptake of HTA recommendations to support decision making with respect to the introduction of three health technologies.

Methods: Using a multidimensional framework, based upon a combination of theoretical models, a case study was conducted. A total of twenty-eight semistructured interviews were done with physicians from fifteen hospitals and other stakeholders in Catalonia. Interview content was analyzed iteratively and classified according to theoretical dimensions and contextual factors.

Results: At the sociopolitical level, factors related to the organization and financing of the health system were found to affect the utilization of HTA recommendations. At the healthcare organization level, existing collaborations between the hospital and the HTA agency favored the integration of recommendations into practices. Formalism in the organization also influenced the utilization of HTA recommendations. At the professional level, the high degree of autonomy of specialists, the importance of peers and collegial control, and the definition of professional roles and responsibilities influenced physicians' willingness to integrate HTA recommendations into their practice.

Conclusions: This study offers a comprehensive framework to understand the complex dynamics that affect adoption of health technologies in organizational and professional practices. The findings suggest some avenues to promote the integration of HTA recommendations into practices and, thus, increase the utilization of scientific evidence to support decision making in health care.

Objectives: The cost-effectiveness of adding a human papillomavirus (HPV) vaccination program in 12-year-old females to the recommended cervical cancer screening in Belgium is examined. Moreover, the health and economic consequences of a potential decline in screening uptake after initiation of a HPV vaccination program are investigated.

Methods: A static Markov model is developed to estimate the direct effect of vaccination on precancerous lesions and cervical cancers.

Results: Vaccination is estimated to avoid 20 percent of the cervical cancers occurring in a 12-year-old girls' cohort and to cost €32,665 per quality-adjusted life-year (QALY) gained (95 percent credibility interval [CrI]: €17,447 to €68,078), assuming a booster injection after 10 years, a limited duration of protection and discounting costs and effects at 3 percent and 1.5 percent, respectively. Assuming lifelong protection, HPV vaccination is estimated to cost €14,382 (95 percent CrI: €9,238 to €25,644) per QALY gained, while avoiding 50 percent of the cervical cancer cases. In the base-case, a 10 percent reduction in screening compliance after vaccination obliterates the effect of vaccination on cervical cancer cases avoided, whereas further declines in the level of screening compliance even turned out to be detrimental for the cohort's health, inducing a mean loss in QALYs and life-year gained compared with the situation prevaccination.

Conclusions: An HPV vaccination program should only be considered if the level of screening after vaccination can be maintained.

Four studies, each on health technology assessment (HTA) in a different country, are presented in this volume. Conveying differing levels of sensitivity to political aspects of HTA, their storylines are similar in terms of the importance of the institutional structures that produce HTA and mediate its influence on health policy decision making. Regarding the internal politics of HTA, the latter appears to have developed in a relatively depoliticized environment, supported by a dense and varied web of institutional sites for funding, production, and consumption of HTA, buffered from the capricious impacts of electoral politics. Regarding external politics, HTA in all the countries began with relatively politically innocuous studies of technologies recognized to be of major import to national health systems or researcher-initiated studies. However, with increased focus in health systems on explicit determination of health benefits baskets, the role of HTA has become more high profile. This means that political accountability for the entire HTA process will increase. The implication is that future management of HTA programs will require self-conscious attention to the building of institutions capable of handling the delicate process of integrating science and politics in health policy.

Background: In 1994/95, two genes, BRCA1/2, associated with a predisposition to breast or ovarian cancer were identified. Genetic testing of deleterious BRCA1/2 mutations consequently can be proposed to individuals with a family history of breast or ovarian cancer to identify who is at risk. The granting of U.S. patents on BRCA1/2 to a privately owned company has led to the monopoly use of a unique technique (Direct Sequencing of the gene, DS) for BRCA1/2 testing in this country. Alternative strategies using prescreening techniques, however, have been experienced worldwide.

Methods: On the basis of data collected at three laboratories of French public hospitals, we carried out a cost-effectiveness study comparing DS to 19 alternative strategies with the number of deleterious BRCA1 mutations detected as the outcome.

Results: Results show that the DS strategy presents the highest average cost per mutation detected (9,882.5 °) and that there exist strategies using prescreening techniques that can reach similar effectiveness while reducing total costs. Moreover, other strategies can obtain a four- to sevenfold reduction in the average cost per mutation detected as soon as some rates of false negatives (2% to 13%) are deemed to be acceptable.

Conclusions: Results suggest that gene patents with a very broad scope, covering all potential medical applications, may prevent health care systems from identifying and adopting the most efficient genetic testing strategies due to the monopoly granted for the exploitation of the gene. Policy implications for regulatory authorities, in the current context of the extension of BRCA1/2 patents in other countries, are discussed.