Health technology reassessment: the art of the possible

BACKGROUND: Health technology reassessment (HTR) is "a structured, evidence-based assessment of the clinical, social, ethical, and economic effects of a technology currently used in the healthcare system, to inform optimal use of that technology in comparison to its alternatives." The purpose of this study is to describe the key themes in the context of current HTR activities and propose a way forward for this newly emerging field. METHODS: Data were gathered from a workshop held as part of the 2012 Canadian Agency for Drugs and Technology in Health (CADTH) symposium. The workshop consisted of two panel presentations followed by discussion; data gathered, including presentations and rich audience discussion transcripts, were analyzed for key themes emerging in the field of HTR using constant comparative analysis. RESULTS: The language chosen to describe HTR will set the tone for engagement. The identification of champions at multiple levels and political will are essential. Key lessons from international experience are: disinvestment is difficult, focus on clinical areas not specific technologies, identify clear goals of the HTR agenda. Six key themes were identified to move the HTR agenda forward: emphasize integration over segregation, focus on development of HTR methods and processes, processes are context-specific but lessons must be shared, build capacity in synergistic interdisciplinary fields, develop meaningful stakeholder engagement, strengthen postimplementation monitoring and evaluation. CONCLUSIONS: To move this field forward, we must continue to build on international experiences with a focus on developing novel methodological approaches to generating, incorporating, and implementing evidence into policy and practice.Gail MacKean, Tom Noseworthy, Adam G. Elshaug, Laura Leggett, Peter Littlejohns, Joan Berezanski and Fiona Clemen

Managing juvenile idiopathic arthritis within the context of their life:What we learnt from children and youth living with juvenile idiopathic arthritis and their parents

Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and causes short- and long-term disability. Optimal management requires pharmacologic and non-pharmacologic interventions. Few studies have explored the youth and family experience of the management of JIA. This study's objective was to explore the management experience of youth with JIA and their parents. Methods: This qualitative study used semi-structured interviews with youth 12–18 years of age with JIA receiving biological medication and parents of children with JIA on biological medication. Participants were recruited in clinics using convenience sampling. A thematic analysis approach was employed for data analysis. Results: Nine youth and 14 parents participated. Four themes were identified that encompassed an overarching theme of participants managing JIA within the context of their life: aspects of life affected by JIA and its management, lived experience with JIA management, medication decision-making, and involvement in decision-making. Juvenile idiopathic arthritis management is situated within the context of their life but is normally (outside acute events) not central. Conclusion: Two dimensions were added to those in the literature: parents' overall approaches to health and the sense of urgency surrounding decision-making. Our findings reinforce the importance of person- and family-centred care in paediatric rheumatology. That is, identifying what matters most to youth and their parents given their current life circumstances to provide a foundation for discussions of how they want to manage their JIA.</p

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor

Objectives We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer. Methods We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II–IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL). Results The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3–4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms. Conclusion mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782

The National Lung Matrix Trial of personalized therapy in lung cancer

The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke1,2,3. As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug–biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy—including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug–biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke

A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer

The triple drug combination consisting of irinotecan, oxaliplatin and 5-fluorouracil (FOLFOXIRI) has demonstrated higher activity and efficacy compared to the doublet FOLFIRI. 5-Fluorouracil could be substituted in FOLFOXIRI regimen by capecitabine, an oral fluoropyrimidine with similar efficacy. Recently, a dose-finding trial has demonstrated the feasibility of the combination of irinotecan, oxaliplatin and capecitabine (XELOXIRI) and established their recommended doses. The aim of this study was to evaluate the activity of XELOXIRI. A total of 36 patients with unresectable metastatic colorectal cancer received irinotecan 165 mg m−2 and oxaliplatin 85 mg m−2 on day 1 plus capecitabine 2000 mg m−2 per day orally in two doses from day 1 to day 7, every 2 weeks. Grade 3–4 toxicities were infrequent, expect for neutropenia and diarrhoea, which were each observed in 30% of patients. Two complete and twenty-two partial responses were obtained, corresponding to an overall response rate of 67% (95% CI 51.4–82%). After a median follow-up of 17.7 months, the median progression-free and overall survival were 10.1 and 17.9 months, respectively

Organizational impact of evidence-informed decision making training initiatives : a case study comparison of two approaches

Background The impact of efforts by healthcare organizations to enhance the use of evidence to improve organizational processes through training programs has seldom been assessed. We therefore endeavored to assess whether and how the training of mid- and senior-level healthcare managers could lead to organizational change. Methods We conducted a theory-driven evaluation of the organizational impact of healthcare leaders’ participation in two training programs using a logic model based on Nonaka’s theory of knowledge conversion. We analyzed six case studies nested within the two programs using three embedded units of analysis (individual, group and organization). Interviews were conducted during intensive one-week data collection site visits. A total of 84 people were interviewed. Results We found that the impact of training could primarily be felt in trainees’ immediate work environments. The conversion of attitudes was found to be easier to achieve than the conversion of skills. Our results show that, although socialization and externalization were common in all cases, a lack of combination impeded the conversion of skills. We also identified several individual, organizational and program design factors that facilitated and/or impeded the dissemination of the attitudes and skills gained by trainees to other organizational members. Conclusions Our theory-driven evaluation showed that factors before, during and after training can influence the extent of skills and knowledge transfer. Our evaluation went further than previous research by revealing the influence—both positive and negative—of specific organizational factors on extending the impact of training programs

Effectiveness of a family-centered method for the early identification of social-emotional and behavioral problems in children: a quasi experimental study

Background: Social-emotional and behavioral problems are common in childhood. Early identification of these is important as it can lead to interventions which may improve the child's prognosis. In Dutch Preventive Child Healthcare (PCH), a new family-centered method has been implemented to identify these problems in early childhood. Its main features are consideration of the child's developmental context and empowerment of parents to enhance the developmental context. Methods/design: In a quasi-experimental study, embedded in routine PCH in the Netherlands, regions in which the family-centered method has been implemented (intervention condition) will be compared to "care as usual" regions (control condition). These regions are comparable in regard to socio-demographic characteristics. From more than 3,500 newborn babies, 18-month follow-up data on social-emotional and behavioral development will be obtained. PCH professionals will assess development during each routine well-child visit; participating parents will fill in standardized questionnaires. Primary outcomes in the study are the proportion of social-emotional and behavioral problems identified by PCH professionals in children aged 2-14 and 18 months in both conditions, and the proportion of agreement between the assessment of PCH professionals and parents. In addition, the added value of the family-centered approach will be assessed by comparing PCH findings with standardized questionnaires. The secondary outcomes are the degree to which the needs of parents are met and the degree to which they are willing to disclose concerns. Discussion: The family-centered method seems promising for early identification of social-emotional and behavioral problems. The results of this study will contribute to evidence-based public health. Trial registration: NTR2681