Lotte Maria Gertruda Steuten

Early assessment of medical technologies to inform product development and market access

Worldwide, billions of dollars are invested in medical product development and there is an increasing pressure to maximize the revenues of these investments. That is, governments need to be informed about the benefits of spending public resources, companies need more information to manage their product development portfolios and even universities may need to direct their research programmes in order to maximize societal benefits. Assuming that all medical products need to be adopted by the heavily regulated healthcare market at one point in time, it is worthwhile to look at the logic behind healthcare decision making, specifically, decisions on the coverage of medical products and decisions on the use of these products under competing and uncertain conditions.With the growing tension between leveraging economic growth through R&D spending on the one hand and stricter control of healthcare budgets on the other, several attempts have been made to apply the health technology assessment (HTA) methodology to earlier stages of technology development and implementation. For instance, horizon scanning was introduced to systematically assess emerging technologies in order to inform health policy. Others have introduced iterative economic evaluation, e.g. economic evaluations in earlier stages of clinical research. However, most of these methods are primarily intended to support governments in making decisions regarding potentially expensive new medical products. They do not really inform biomedical product developers on the probability of return on investment, nor do they inform about the market needs and specific requirements of technologies in development. It is precisely this aspect that increasingly receives attention, i.e. is it possible to use HTA tools and methods to inform biomedical product development and to anticipate further development and market access. Several methods have been used in previous decades, but have never been compiled in a comprehensive review.The main objective of this article was to provide an overview of previous work and methods in the field of early HTA, and to put these approaches in perspective through a conceptual framework introduced in this paper. A particular goal of the review was to familiarize decision makers with available techniques that can be employed in early-stage decision making, and to identify opportunities for further methodological growth in this emerging field of HTA.

Integrating health economics modeling in the product development cycle of medical devices: A Bayesian approach

OBJECTIVES Medical device companies are under growing pressure to provide health-economic evaluations of their products. Cost-effectiveness analyses are commonly undertaken as a one-off exercise at the late stage of development of new technologies; however, the benefits of an iterative use of economic evaluation during the development process of new products have been acknowledged in the literature. Furthermore, the use of Bayesian methods within health technology assessment has been shown to be of particular value in the dynamic framework of technology appraisal when new information becomes available in the life cycle of technologies. METHODS In this study, we set out a methodology to adapt these methods for their application to directly support investment decisions in a commercial setting from early stages of the development of new medical devices. RESULTS AND CONCLUSIONS Starting with relatively simple analysis from the very early development phase and proceeding to greater depth of analysis at later stages, a Bayesian approach facilitates the incorporation of all available evidence and would help companies to make better informed choices at each decision point.

Quality of integrated chronic care measured by patient survey: identification, selection and application of most appropriate instruments

Objective  To identify the most appropriate generic instrument to measure experience and/or satisfaction of people receiving integrated chronic care.

Identifying potentially cost effective chronic care programs for people with COPD

Objective To review published evidence regarding the cost effectiveness of multi-component COPD programs and to illustrate how potentially cost effective programs can be identified. Methods Systematic search of Medline and Cochrane databases for evaluations of multi-component disease management or chronic care programs for adults with COPD, describing process, intermediate, and end results of care. Data were independently extracted by two reviewers and descriptively summarized. Results Twenty articles describing 17 unique COPD programs were included. There is little evidence for significant improvements in process and intermediate outcomes, except for increased provision of patient self-management education and improved disease-specific knowledge. Overall, the COPD programs generate end results equivalent to usual care, but programs containing ≥3 components show lower relative risks for hospitalization. There is limited scope for programs to break-even or save money. Conclusion Identifying cost effective multi-component COPD programs remains a challenge due to scarce methodologically sound studies that demonstrate significant improvements on process, intermediate and end results of care. Estimations of potential cost effectiveness of specific programs illustrated in this paper can, in the absence of ‘perfect data’, support timely decision-making regarding these programs. Nevertheless, well-designed health economic studies are needed to decrease the current decision uncertainty.

Meta‐analysis of the effectiveness of chronic care management for diabetes: investigating heterogeneity in outcomes

PURPOSE The study aims to support decision making on how best to redesign diabetes care by investigating three potential sources of heterogeneity in effectiveness across trials of diabetes care management. METHODS Medline, CINAHL and PsycInfo were searched for systematic reviews and empirical studies focusing on: (1) diabetes mellitus; (2) adult patients; and (3) interventions consisting of at least two components of the chronic care model (CCM). Systematic reviews were analysed descriptively; empirical studies were meta-analysed. Pooled effect measures were estimated using a meta-regression model that incorporated study quality, length of follow-up and number of intervention components as potential predictors of heterogeneity in effects. RESULTS Overall, reviews (n = 15) of diabetes care programmes report modest improvements in glycaemic control. Empirical studies (n = 61) show wide-ranging results on HbA1c, systolic blood pressure and guideline adherence. Differences between studies in methodological quality cannot explain this heterogeneity in effects. Variety in length of follow-up can explain (part of) the variability, yet not across all outcomes. Diversity in the number of included intervention components can explain 8-12% of the heterogeneity in effects on HbA1c and systolic blood pressure. CONCLUSIONS The outcomes of chronic care management for diabetes are generally positive, yet differ considerably across trials. The most promising results are attained in studies with limited follow-up (<1 year) and by programmes including more than two CCM components. These factors can, however, explain only part of the heterogeneity in effectiveness between studies. Other potential sources of heterogeneity should be investigated to ensure implementation of evidence-based improvements in diabetes care.

Focal salvage iodine-125 brachytherapy for prostate cancer recurrences after primary radiotherapy: a retrospective study regarding toxicity, biochemical outcome and quality of life.

PURPOSE Whole-gland salvage for recurrent prostate cancer (PCa) shows high failure and toxicity rates. Early and adequate localization of recurrences enables focal salvage, thereby potentially improving functional outcomes, while maintaining cancer control. MATERIALS AND METHODS Retrospective analysis yielded 20 focal salvage I125 brachytherapy patients for locally recurrent PCa after primary radiotherapy. Tumor was defined by multiparametric MRI and correspondence with transrectal biopsies. Dose data were obtained intra-operatively. The tumor was prescribed ⩾144 Gy. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 4 (CTCAE-4). Biochemical failure (BF) was defined using the Phoenix criteria (PSA-nadir + 2.0 ng/ml). Quality of life (QoL) was measured by SF-36 Health Survey and European Organization of Research and Treatment of Cancer (EORTC) C30+3 and PR25 questionnaires. RESULTS With a median follow-up of 36 months (range 10-45), six patients experienced BF, of which three had no initial response. Grade 3 genitourinary (GU) toxicity occurred in one patient (a urethral stricture). The five previously potent patients retained erectile function. QoL remained decreased with regard to urinary symptoms. CONCLUSION Focal salvage I125 brachytherapy showed one grade 3 GU toxicity in the 20 treated patients. Biochemical response and QoL were acceptable.

Chronic care management for patients with COPD : A critical review of available evidence

RATIONALE, AIMS AND OBJECTIVES Clinical diversity and methodological heterogeneity exists between studies on chronic care management. This study aimed to examine the effectiveness of chronic care management in chronic obstructive pulmonary disease (COPD) while taking heterogeneity into account, enabling the understanding of and the decision making about such programmes. Three investigated sources of heterogeneity were study quality, length of follow-up, and number of intervention components. METHODS We performed a review of previously published reviews and meta-analyses on COPD chronic care management. Their primary studies that were analyzed as statistical, clinical and methodological heterogeneity were present. Meta-regression analyses were performed to explain the variances among the primary studies. RESULTS Generally, the included reviews showed positive results on quality of life and hospitalizations. Inconclusive effects were found on emergency department visits and no effects on mortality. Pooled effects on hospitalizations, emergency department visits and quality of life of primary studies did not reach significant improvement. No effects were found on mortality. Meta-regression showed that the number of components of chronic care management programmes explained present heterogeneity for hospitalizations and emergency department visits. Four components showed significant effects on hospitalizations, whereas two components had significant effects on emergency department visits. Methodological study quality and length of follow-up did not significantly explain heterogeneity. CONCLUSIONS This study demonstrated that COPD chronic care management has the potential to improve outcomes of care; heterogeneity in outcomes was explained. Further research is needed to elucidate the diversity between COPD chronic care management studies in terms of the effects measured and strengthen the support for chronic care management.

Cost-utility of a disease management program for patients with asthma

OBJECTIVES The long-term cost-utility of a disease management program (DMP) for adults with asthma was assessed compared to usual care. METHODS A DMP for patients with asthma has been developed and implemented in the region of Maastricht (The Netherlands). By integrating care, the program aims to continuously improve quality of care within existing budgets. A clinical trial was performed over a period of 15 months to collect data on costs and effects of the program and usual care. These data were used to inform a probabilistic decision-analytic model to estimate the 5-year impact of the program beyond follow-up. A societal perspective was adopted, with outcomes assessed in terms of costs per quality-adjusted life-year (QALY). RESULTS The DMP is associated with a gain in QALYs compared to usual care (2.7+/-.2 versus 3.4+/-.8), at lower costs (3,302+/-314 euro versus 2,973+/-304 euro), thus leading to dominance. The probability that disease management is the more cost-effective strategy is 76 percent at a societal willingness to pay (WTP) for an additional QALY of 0 euro, reaching 95 percent probability at a WTP of 1,000 euro per additional QALY. CONCLUSIONS Organizing health care according to the principles of disease management for adults with asthma has a high probability of being cost-effective and is associated with a gain in QALYs at lower costs.

A disease management programme for patients with diabetes mellitus is associated with improved quality of care within existing budgets

Aim  To assess the impact of a disease management programme for patients with diabetes mellitus (Type 1 and Type 2) on cost‐effectiveness, quality of life and patient self‐management. By organizing care in accordance with the principles of disease management, it is aimed to increase quality of care within existing budgets.

Are we measuring what matters in health technology assessment of disease management? Systematic literature review

OBJECTIVES An overview was produced of indicators currently used to assess disease management programs and, based on these findings, provide a framework regarding sets of indicators that should be used when taking the aims and types of disease management programs into account. METHODS A systematic literature review was performed. RESULTS Thirty-six studies met the inclusion criteria. It appeared that a link between aims of disease management and evaluated structure, process, as well as outcome indicators does not exist in a substantial part of published studies on disease management of diabetes and asthma/chronic obstructive pulmonary disease, especially when efficiency of care is concerned. Furthermore, structure indicators are largely missing from the evaluations, although these are of major importance for the interpretation of outcomes for purposes of decision-making. Efficiency of disease management is mainly evaluated by means of process indicators; the use of outcome indicators is less common. Within a framework, structure, process, and outcome indicators for effectiveness and efficiency are recommended for each type of disease management program. CONCLUSIONS The link between aims of disease management and evaluated structure, process, and outcome indicators does not exist in a substantial part of published studies on disease management. The added value of this study mainly lies in the development of a framework to guide the choice of indicators for health technology assessment of disease management.