Validating a generic cancer consumer quality index in eight European countries, patient reported experiences and the influence of cultural differences.

BACKGROUND: Taking patient centeredness into account is important in healthcare. The European Cancer Consumer Quality Index (ECCQI) is a validated tool for international benchmarking of patient experiences and satisfaction. This study aimed to further validate the ECCQI in larger and more uniform groups of high volume tumours such as breast and prostate cancer. A second objective was the verification of the influence of cultural factors of the country to determine its possible use in international benchmarking. METHODS: Data from two survey studies in eight European countries were combined. Socio-demographic correlations were analysed with Kruskall-Wallis and Mann-Whitney tests. Cronbach's alpha was calculated to validate internal consistency. Influences of masculinity (MAS), power distance (PD) and uncertainty avoidance (UA) were determined by linear regression analysis in a general model and subgroup models. RESULTS: A total of 1322 surveys were included in the analysis (1093 breast- and 348 prostate cancer patients). Cronbach's alpha was good (α ≥ 0.7) or acceptable (0.5 ≤ α ≤ 0.7) in 8 out of 9 questionnaire categories, except in the category 'Safety' (α = 0.305). Overall ECCQI scores ranged from 22.1 to 25.1 between countries on a 1-35 scale (categories had a 1-4 scale). In certain subcategories such as 'Organisation' (range 2.2 vs 3.0) and 'Supervision & Support' (range 3.0 vs 3.8) a large difference was observed between countries. Differences in 'Overall opinion' were however small: mean scores of 3.7 vs 3.9, whereas median scores were all the maximum of 4.0. Power distance was positively associated with higher patient satisfaction scores whereas Uncertainty avoidance was negatively associated with these scores. Masculinity was only associated with patient satisfaction scores in lower educated patients. We found the highest impact of culture on overall scores in Hungary and Portugal and the lowest in Romania. CONCLUSIONS: The ECCQI shows high internal consistency in all categories except 'Safety'. Especially in separate categories and overall ECCQI scores the questionnaire showed discriminative value. This study showed a positive correlation of power distance and a negative correlation for uncertainty avoidance in some countries. When using the ECCQI for international benchmarking these two dimensions of culture should be taken into account.

(Cost-)effectiveness of an internet-based physical activity support program (with and without physiotherapy counselling) on physical activity levels of breast and prostate cancer survivors: design of the PABLO trial.

BACKGROUND: Higher levels of physical activity (PA) after treatment are associated with beneficial effects on physical and psychosocial functioning of cancer survivors. However, survivors often do not meet the recommended levels of PA. In order to promote PA, we developed a closed internet-based program. The aim of the study is to evaluate the (cost-)effectiveness of an internet-based PA-promotion program, alone or combined with physiotherapy counselling, compared to usual care, on PA-levels of breast or prostate cancer survivors. In this multicenter randomised controlled trial (RCT), breast or prostate cancer survivors who completed their primary treatment 3-12 months earlier, will be randomised to either 6-months access to a fully-automated internet-based intervention alone, an internet-based intervention plus remote support by a physiotherapist, or a control group. The intervention is based on the Transtheoretical Model and includes personalized feedback, information, video's and assignments. Additionally, in a second arm, physiotherapy counselling is provided through monthly scheduled and on-demand telephone calls. The control group will receive usual care and a leaflet with PA guidelines. METHODS: At baseline, 6 and 12 months, the primary outcome (PA) will be measured during 7 consecutive days by accelerometers. Secondary outcomes are self-reported PA, fatigue, mood, health-related quality of life, and costs. The group differences for primary and secondary outcomes will be analyzed using linear mixed models. DISCUSSION: If proven to be (cost)effective, this internet-based intervention, either alone or in combination with telephone support, will be a welcome addition to previous RCT's. TRIAL REGISTRATION: Netherlands trial register (NTR6911), Date of trial registration: December 21, 2017.

Implementing large scale fast track diagnostics in a comprehensive cancer center, pre- and post-measurement data.

BACKGROUND: In general, patients with a cancer suspicion visit the hospital multiple times before diagnosis is completed. Using various "operations management" techniques a few fast track diagnostic services were implemented in the Netherlands Cancer Institute (NKI) in 2006. Growing patient numbers and increasing process complexity, led to diminished service levels. To decrease the amount of patient visits and to extend these services beyond the (obvious) breast cancer services, fast track diagnostics is now implemented for all 18 cancer types that present with a frequency of minimally one per week. METHODS: The throughput time (first visit to diagnosis conversation) was measured before, and after implementation of fast track diagnostics. The process was redesigned closely involving the multidisciplinary teams. In an eclectic approach elements from lean management, theory of constraints and mathematical analysis were used to organize slots per tumor type for MRI, CT, PET and echography. A post measurement was performed after 3 and 6 months. RESULTS: In pre measurement access time was calculated to be 10 to 15 workdays, mean throughput time was 6.0 workdays. It proved possible to design the process of 18 tumors as a fast track, of which 7 as "one stop shop" (diagnosis completed in one visit). Involvement of clinical- and board leadership, massive communication efforts and commitment of physicians to reschedule their work proved decisive. After 3 and 6 months of implementation, the mean access time was 8.2 and 8.7 workdays respectively and mean throughput time was 3.4 and 3.3 workdays respectively. CONCLUSIONS: Throughput- and access time were considerably shortened after implementation of fast track diagnostics for 18 cancer types. The involvement of physicians in reorganizing their work and rapid responding to their needs during the implementation phase were a crucial success factor.

Benchmarking specialty hospitals, a scoping review on theory and practice.

BACKGROUND: Although benchmarking may improve hospital processes, research on this subject is limited. The aim of this study was to provide an overview of publications on benchmarking in specialty hospitals and a description of study characteristics. METHODS: We searched PubMed and EMBASE for articles published in English in the last 10 years. Eligible articles described a project stating benchmarking as its objective and involving a specialty hospital or specific patient category; or those dealing with the methodology or evaluation of benchmarking. RESULTS: Of 1,817 articles identified in total, 24 were included in the study. Articles were categorized into: pathway benchmarking, institutional benchmarking, articles on benchmark methodology or -evaluation and benchmarking using a patient registry. There was a large degree of variability:(1) study designs were mostly descriptive and retrospective; (2) not all studies generated and showed data in sufficient detail; and (3) there was variety in whether a benchmarking model was just described or if quality improvement as a consequence of the benchmark was reported upon. Most of the studies that described a benchmark model described the use of benchmarking partners from the same industry category, sometimes from all over the world. CONCLUSIONS: Benchmarking seems to be more developed in eye hospitals, emergency departments and oncology specialty hospitals. Some studies showed promising improvement effects. However, the majority of the articles lacked a structured design, and did not report on benchmark outcomes. In order to evaluate the effectiveness of benchmarking to improve quality in specialty hospitals, robust and structured designs are needed including a follow up to check whether the benchmark study has led to improvements.

Scenario drafting for early technology assessment of next generation sequencing in clinical oncology.

BACKGROUND: Next Generation Sequencing (NGS) is expected to lift molecular diagnostics in clinical oncology to the next level. It enables simultaneous identification of mutations in a patient tumor, after which targeted therapy may be assigned. This approach could improve patient survival and/or assist in controlling healthcare costs by offering expensive treatment to only those likely to benefit. However, NGS has yet to make its way into the clinic. Health Technology Assessment can support the adoption and implementation of a novel technology, but at this early stage many of the required variables are still unknown. METHODS: Scenario drafting and expert elicitation via a questionnaire were used to identify factors that may act as a barrier or facilitate adoption of NGS-based molecular diagnostics. Attention was paid to predominantly elicit quantitative answers, allowing their use in future modelling of cost-effectiveness. RESULTS: Adequately informing patients and physicians, the latters' opinion on clinical utility and underlying evidence as well as presenting sequencing results within a relevant timeframe may act as pivotal facilitators. Reimbursement for NGS-based testing and accompanying therapies (both general and in case of off-label prescription) was found to be a potential barrier. Competition on the market and demonstrating clinical utility may also be challenging. Importantly, numerous quantitative values for variables related to each of these potential barriers/facilitators, such as such as desired panel characteristics, willingness to pay or the expected number of targets identified per person, were also elicited. CONCLUSIONS: We have identified several factors that may either pose a barrier or facilitate the adoption of NGS in the clinic. We believe acting upon these findings, for instance by organizing educational events, advocating new ways of evidence generation and steering towards the most cost-effective solution, will accelerate the route from bench-to-bedside. Moreover, due to the methodology of expert elicitation, this study provides parameters that can be incorporated in future cost-effectiveness modeling to steer the development of NGS gene panels towards the most optimal direction.

The impact of organisational external peer review on colorectal cancer treatment and survival in the Netherlands.

BACKGROUND: Organisational external peer review was introduced in 1994 in the Netherlands to improve multidisciplinary cancer care. We examined the clinical impact of this programme on colorectal cancer care. METHODS: Patients with primary colorectal cancer were included from 23 participating hospitals and 7 controls. Hospitals from the intervention group were dichotomised by their implementation proportion (IP) of the recommendations from each peer review (high IP vs low IP). Outcome measures were the introduction of new multidisciplinary therapies and survival. RESULTS: In total, 45 705 patients were included (1990-2010). Patients from intervention hospitals more frequently received adjuvant chemotherapy for stage III colon cancer. T2-3/M0 rectal cancer patients from hospitals with a high IP had a higher chance of receiving preoperative radiotherapy (OR 1.31, 95% CI 1.11-1.55) compared with the controls and low IP group (OR 0.75, 95% CI 0.63-0.88). There were no differences in the use of preoperative chemoradiation for T4/M0 rectal cancer. Survival was slightly higher in colon cancer patients from intervention hospitals but unrelated to the phase of the programme in which the hospital was at the time of diagnosis. CONCLUSIONS: Some positive effects of external peer review on cancer care were found, but the results need to be interpreted cautiously due to the ambiguity of the outcomes and possible confounding factors.

Optimized outcome prediction in breast cancer by combining the 70-gene signature with clinical risk prediction algorithms.

Clinical guidelines for breast cancer treatment differ in their selection of patients at a high risk of recurrence who are eligible to receive adjuvant systemic treatment (AST). The 70-gene signature is a molecular tool to better guide AST decisions. The aim of this study was to evaluate whether adding the 70-gene signature to clinical risk prediction algorithms can optimize outcome prediction and consequently treatment decisions in early stage, node-negative breast cancer patients. A 70-gene signature was available for 427 patients participating in the RASTER study (cT1-3N0M0). Median follow-up was 61.6 months. Based on 5-year distant-recurrence free interval (DRFI) probabilities survival areas under the curve (AUC) were calculated and compared for risk estimations based on the six clinical risk prediction algorithms: Adjuvant! Online (AOL), Nottingham Prognostic Index (NPI), St. Gallen (2003), the Dutch National guidelines (CBO 2004 and NABON 2012), and PREDICT plus. Also, survival AUC were calculated after adding the 70-gene signature to these clinical risk estimations. Systemically untreated patients with a high clinical risk estimation but a low risk 70-gene signature had an excellent 5-year DRFI varying between 97.1 and 100 %, depending on the clinical risk prediction algorithms used in the comparison. The best risk estimation was obtained in this cohort by adding the 70-gene signature to CBO 2012 (AUC: 0.644) and PREDICT (AUC: 0.662). Clinical risk estimations by all clinical algorithms improved by adding the 70-gene signature. Patients with a low risk 70-gene signature have an excellent survival, independent of their clinical risk estimation. Adding the 70-gene signature to clinical risk prediction algorithms improves risk estimations and therefore might improve the identification of early stage node-negative breast cancer patients for whom AST has limited value. In this cohort, the PREDICT plus tool in combination with the 70-gene signature provided the best risk prediction.

Factors for a broad technology assessment of comprehensive genomic profiling in advanced cancer, a systematic review.

Comprehensive Genomic Profiling (CGP) allows for the identification of many targets. Reimbursement decision-making is, however, challenging because besides the health benefits of on-label treatments and costs, other factors related to diagnostic and treatment pathways may also play a role. The aim of this study was to identify which other factors are relevant for the technology assessment of CGP and to summarize the available evidence for these factors. After a scoping search and two expert sessions, five factors were identified: feasibility, test journey, wider implications of diagnostic results, organisation of laboratories, and "scientific spillover". Subsequently, a systematic search identified 83 studies collecting mainly evidence for the factors "test journey" and "wider implications of diagnostic results". Its nature was, however, of limited value for decision-making. We recommend the use of comparative strategies, uniformity in outcome definitions, and the inclusion of a comprehensive set of factors in future evidence generation.

A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study.

The 70-gene signature (MammaPrint™) has been developed on retrospective series of breast cancer patients to predict the risk of breast cancer distant metastases. The microarRAy-prognoSTics-in-breast-cancER (RASTER) study was the first study designed to prospectively evaluate the performance of the 70-gene signature, which result was available for 427 patients (cT1-3N0M0). Adjuvant systemic treatment decisions were based on the Dutch CBO 2004 guidelines, the 70-gene signature and doctors' and patients' preferences. Five-year distant-recurrence-free-interval (DRFI) probabilities were compared between subgroups based on the 70-gene signature and Adjuvant! Online (AOL) (10-year survival probability <90% was defined as high-risk). Median follow-up was 61.6 months. Fifteen percent (33/219) of the 70-gene signature low-risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of the 70-gene signature high-risk patients. The 5-year DRFI probabilities for 70-gene signature low-risk (n = 219) and high-risk (n = 208) patients were 97.0% and 91.7%. The 5-year DRFI probabilities for AOL low-risk (n = 132) and high-risk (n = 295) patients were 96.7% and 93.4%. For 70-gene signature low-risk-AOL high-risk patients (n = 124), of whom 76% (n = 94) had not received ACT, 5-year DRFI was 98.4%. In the AOL high-risk group, 32% (94/295) less patients would be eligible to receive ACT if the 70-gene signature was used. In this prospective community-based observational study, the 5-year DRFI probabilities confirmed the additional prognostic value of the 70-gene signature to clinicopathological risk estimations such as AOL. Omission of adjuvant chemotherapy as judged appropriate by doctors and patients and instigated by a low-risk 70-gene signature result, appeared not to compromise outcome.

Effective cooperation influencing performance: a study in Dutch hospitals.

OBJECTIVE: This study focuses on cooperation between physicians and managers and aspects of that cooperation that can provide leads for interventions aimed at enhancing hospital performance. DESIGN: We performed a qualitative study on cooperation between physicians and managers and the influence of that cooperation on hospital performance, and structured the resulting data according to the conditions of Allport's theory on intergroup conflicts. SETTING: General hospitals in the Netherlands. PARTICIPANTS: Thirty physicians (surgical and internal) and managers (strategic, tactic and operational) working in five different hospitals. INTERVENTIONS: In-depth interviews exploring the influence of cooperation between physicians and managers on hospital performance. MAIN OUTCOME MEASURES: Respondents confirmed the complexity of the relationship between physicians and managers and the link between their cooperation and hospital performance. Mentioned aspects such as power and status differences, clarity in decision-making and personal click, are important in determining the effectiveness of the cooperation between physicians and managers. RESULTS: Our study suggests that the effectiveness of cooperation between physicians and managers is related to the uptake of quality initiatives and hospital performance. CONCLUSIONS: The complex relationship between physicians and managers can be referred to as an intergroup conflict situation. We combined Allport's Contact theory conditions with aspects found in our study leading to the following facilitating conditions: address common goals; create interdependent tasks; arrange the support of authorities and respect the medical domain. They will enhance intra-hospital cooperation and therewith hospital performance.

Securing sustainable price levels of innovative anticancer drugs: How to move forward?

BACKGROUND: Novel cancer treatments come with high price tags that compromise access to treatment and the sustainability of healthcare systems. Innovative policies are needed to reach a system that balances innovation and reasonable prices. However, structured approaches to explore, test, and compare innovative proposals are lacking. METHODS: We surveyed experts to evaluate seven promising proposals to reduce drug prices: Transparency, Combined European purchasing, Public drug development, Public clinical trials, Two-part-pricing, Orphan drug reform, and De-linkage. Experts were asked to rank proposals, identify main risk and success factors, and to reflect on missing proposals. The survey was distributed via the networks of the European Cancer League and the Organisation of European Cancer Institutes. RESULTS: Respondents (n = 41) originated from 19 European countries and included stakeholders in health economics, law, medicine, drug discovery, and healthcare policy.Transparency (M = 2; SD = 2 1) and Combined purchasing (M = 3; SD = 1 9) were ranked as the most promising proposals, Two-part pricing (M = 5; SD = 2 3) and De-linkage (M = 6; SD = 2 4) were considered as the most controversial. Main risk categories were a negative impact on R&D (n = 47), technical feasibility (n = 38), and reduced access to medicines (n = 33). Main success categories were international collaboration (n = 34) and agreement of pricing mechanisms (n = 25). Experts considered value assessment and strengthening of the competitive market as additional proposals for further analysis. CONCLUSION: We recommend expanding on these results to further specify actionable policies that can be tested. Pilots should consider uncertainties and conducted with a focus on international collaboration, preferably in cooperation with the pharmaceutical industry.

Effects of and Lessons Learned from an Internet-Based Physical Activity Support Program (with and without Physiotherapist Telephone Counselling) on Physical Activity Levels of Breast and Prostate Cancer Survivors: The PABLO Randomized Controlled Trial.

BACKGROUND: We developed an Internet-based physical activity (PA) support program (IPAS), which is embedded in a patient portal. We evaluated the effectiveness and costs of IPAS alone (online only) or IPAS combined with physiotherapist telephone counselling (blended care), compared to a control group. METHODS: Breast or prostate cancer survivors, 3-36 months after completing primary treatment, were randomized to 6-months access to online only, blended care, or a control group. At baseline and 6-month post-baseline, minutes of moderate-to-vigorous PA (MVPA) were measured by accelerometers. Secondary outcomes were self-reported PA, fatigue, mood, health-related quality of life, attitude toward PA, and costs. (Generalized) linear models were used to compare the outcomes between groups. RESULTS: We recruited 137 survivors (participation rate 11%). We did not observe any significant between-group differences in MVPA or secondary outcomes. Adherence was rather low and satisfaction scores were low to moderate, with better scores for blended care. Costs for both interventions were low. CONCLUSIONS: Recruitment to the study was challenging and the interventions were less efficacious than anticipated, which led to lessons learned for future trials. Suggestions for future research are as follows: improved accessibility of the support program, increased frequency of support, and use of activity trackers.