Patient and citizen participation at the organizational level in health technology assessment: an exploratory study in five jurisdictions.

OBJECTIVE: While patient participation in individual health technology assessments (HTAs) has been frequently described in the literature, patient and citizen participation at the organizational level is less described and may be less understood and practiced in HTA bodies. We aimed to better understand its use by describing current practice. METHOD: To elicit descriptive case studies and insights we conducted semi-structured interviews and open-ended questionnaires with HTA body staff and patients and citizens participating at the organizational level in Belgium, France, Quebec, Scotland, and Wales. RESULTS: We identified examples of organizational participation in managerial aspects: governance, defining patient involvement processes, evaluation processes and methods, and capacity building. Mechanisms included consultation, collaboration, and membership of standing (permanent) groups. These were sometimes combined. Participants were usually from umbrella patient organizations and patient associations, as well as individual patients and citizens. DISCUSSION: Although the concept, participation at the organizational level, is not well-established, we observed a trend toward growth in each jurisdiction. Some goals were shared for this participation, but HTA bodies focused more on instrumental goals, especially improving participation in HTAs, while patients and citizens were more likely to offer democratic and developmental goals beyond improving participation processes. CONCLUSION: Our findings provide rationales for organizational-level participation from the perspectives of HTA bodies and patients. The case studies provide insights into how to involve participants and who may be seen as legitimate participants. These findings may be useful to HTA bodies, the patient sector, and communities when devising an organizational-level participation framework.

Cost-effectiveness of strategies to control the spread of carbapenemase-producing Enterobacterales in hospitals: a modelling study.

BACKGROUND: Spread of resistant bacteria causes severe morbidity and mortality. Stringent control measures can be expensive and disrupt hospital organization. In the present study, we assessed the effectiveness and cost-effectiveness of control strategies to prevent the spread of Carbapenemase-producing Enterobacterales (CPE) in a general hospital ward (GW). METHODS: A dynamic, stochastic model simulated the transmission of CPE by the hands of healthcare workers (HCWs) and the environment in a hypothetical 25-bed GW. Input parameters were based on published data; we assumed the prevalence at admission of 0.1%. 12 strategies were compared to the baseline (no control) and combined different prevention and control interventions: targeted or universal screening at admission (TS or US), contact precautions (CP), isolation in a single room, dedicated nursing staff (DNS) for carriers and weekly screening of contact patients (WSC). Time horizon was one year. Outcomes were the number of CPE acquisitions, costs, and incremental cost-effectiveness ratios (ICER). A hospital perspective was adopted to estimate costs, which included laboratory costs, single room, contact precautions, staff time, i.e. infection control nurse and/or dedicated nursing staff, and lost bed-days due to prolonged hospital stay of identified carriers. The model was calibrated on actual datasets. Sensitivity analyses were performed. RESULTS: The baseline scenario resulted in 0.93 CPE acquisitions/1000 admissions and costs 32,050 €/1000 admissions. All control strategies increased costs and improved the outcome. The efficiency frontier was represented by: (1) TS with DNS at a 17,407 €/avoided CPE case, (2) TS + DNS + WSC at a 30,700 €/avoided CPE case and (3) US + DNS + WSC at 181,472 €/avoided CPE case. Other strategies were dominated. Sensitivity analyses showed that TS + CP might be cost-effective if CPE carriers are identified upon admission or if the cases have a short hospital stay. However, CP were effective only when high level of compliance with hand hygiene was obtained. CONCLUSIONS: Targeted screening at admission combined with DNS for identified CPE carriers with or without weekly screening were the most cost-effective options to limit the spread of CPE. These results support current recommendations from several high-income countries.

Inequities in cancer drug development in terms of unmet medical need.

This study measures inequality and inequity in the distribution of clinical trials on cancer drug development between 1996 and 2016, comparing the number of clinical trials with cancer need, proxied by prevalence, incidence, or survival rates for both rare and non-rare cancers. We leverage a unique global database of clinical trials activity and costs between 1996 and 2016, constructed for 227 different cancer types to measure for rare and non-rare cancers: i) inequalities and inequity of clinical trial activity, considering all trials as well as split by R&D stage; ii) inequalities and inequity in R&D investment proxied by trial enrollment and duration; iii) evolution of inequity over time. Inequalities are measured with concentration curves and indices and inequities measured with the health inequity index. We find four important results. First, we show pro-low need inequity across cancer types for both rare and non-rare cancers, for all need proxies. Second, we show inequity differs across R&D stages and between rare and non-rare cancers. The distribution of clinical trials for non-rare cancers disproportionately favors low-need non-rare cancers from earlier to later stages of R&D, whilst for rare cancers this only occurs in Phase 2 trials. Third, inequity analyses in R&D investment show that only trial enrollment for rare cancers and trial duration for non-rare cancers are disproportionately concentrated among low-need cancers. Finally, while pro-low need inequity has persisted between 1996 and 2016 for non-rare cancers, it has faded for rare cancers post-EU orphan drugs' legislation.

The contribution of French patient and consumer groups to health technology assessments over a 2-year period: an observational retrospective study.

BACKGROUND: In 2017, The French National Authority for Health (HAS) created an open, online, systematic contribution process to enable patient and consumer groups (PCGs) to contribute to health technology assessment (HTA) carried out to aid public authorities in reimbursement and pricing decision making. OBJECTIVES: This retrospective study analyzes how French PCGs contributed to the HTA process within the HAS for the first 2 years of this new mechanism. METHODS: PCG contributions received between 01 January 2017 and 31 December 2018 and the recording of deliberations leading to reports of the corresponding HTAs were included. Analysis grids were designed by the investigators with 5 rounds of refinement tests on 10 random PCG contributions and the reports. Systematic data extraction was then performed separately by two investigators. PCG answers to the open-question templates and the related final HTA report published by the HAS were analyzed. RESULTS: Seventy-nine contributions from 44 PCGs were received and analyzed by the HAS for 78 out of the 592 HTAs performed for drugs or medical devices during the 2-year period. Twenty-five percent of the HTAs performed for drugs received at least one contribution. The contributions covered quality-of-life aspects, access to care, and personal and family impact. Membership and budget of the contributing PCGs varied greatly. CONCLUSIONS: The experience gained in the first 2 years demonstrates the feasibility of the process and the fact that PCG contribution actually provides relevant input on the patient perspective for HTAs used for reimbursement decisions. The challenges identified on the side of PCGs were time constraints and human resources.

Evaluating the Impact of Intensive Case Management for Severe Vocational Injuries on Work Incapacity and Costs.

Purpose This study investigates the impact of an intensive case management program on sick leave days, permanent work incapacity levels and treatment costs for severe vocational injuries set up by the French National Insurance Fund in five health insurance districts. Methods The method employed relies on a four-step matching procedure combining Coarsened Exact Matching and Propensity Score Matching, based on an original administrative dataset. Average Treatment effects on the Treated were estimated using a parametric model with a large set of covariates. Results After one-year follow-up, workers in the treatment group had higher sickness absence rates, with 22 extra days, and the program led to 2.7 (95% CI 2.3-3.1) times more diagnoses of permanent work incapacity in the treatment group. With an estimated yearly operational cost of 2,722 € per treated worker, the average total extra treatment cost was 4,569 € for treated workers, which corresponds to a cost increase of 29.2% for the insurance fund. Conclusions The higher costs found for the treatment group are mainly due to longer sick leave duration for the moderate severity group, implying higher cash transfers in the form of one-off indemnities. Even though workers in the treated group have more diagnoses of permanent work incapacity, the difference of severity between groups is small. Our results on longer sick leave duration are partly to be explained by interactions between the case managers and the occupational physicians that encouraged patients to stay longer off-work for better recovery, despite the higher costs that this represented for the insurance fund and the well-documented adverse side effects of longer periods off-work.

Effectiveness and efficiency of teleimaging in the transplantation process: a mixed method protocol.

BACKGROUND: The transplantation process usually takes place without transplant teams being able to use imaging data to assess graft quality. The decision of whether to go get the graft or not is therefore limited and suboptimal. "Cristal images" is a teleimaging project allowing real-time visualization of images of the organs of the donor. The objective of our study is to assess whether the use of a secure teleimaging can improve the effectiveness and efficiency of the procurement and transplantation processes. METHODS: We will use the exhaustive national registry of organ allocation and transplantation, and compare outcomes before the deployment of "Cristal images" (years 2015-2016) and after it becomes operational (years 2018-2019) for heart, lung, liver and kidney transplant in a before-after study, combined with a preference elicitation study. The primary endpoint will be the number of successful organ transplantations. Secondary endpoints will be related to the efficiency of the transplant process (decision making, transportation, cost) and a preference elicitation study will determine the relative preferences of transplant teams towards few "Cristal images"' components or potential developments, which are yet to be determined through a qualitative analysis based on interviews with professionals. DISCUSSION: This study will provide stakeholders data on the efficiency of real-time visualization for transplant teams and identify the levers likely to influence the technology use among these teams. TRIAL REGISTRATION: clinicaltrials.gov: NCT03201224 , 13 June 2017, retrospectively registered.

Parents' and children's comprehension and decision in a paediatric early phase oncology trial: a prospective study.

OBJECTIVE: To analyse parents' and children's understanding of consent information and assess their decision-making process in paediatric oncology. DESIGN: Prospective observational study. SETTINGS: Eleven French paediatric oncology units. PATIENTS: Parents and children who have been asked to give consent for participation in an early phase trial. INTERVENTIONS: Thirty-seven children and 119 parents were questioned using an audio-recorded semistructured interview. MAIN OUTCOME MEASURES: The participants' understanding of nine elements of the informed consent was assessed by comparing their answers with the informed consent leaflet. Their decision-making process was also evaluated. RESULTS: Most parents and children had an excellent understanding regarding their participation in a clinical trial (respectively 88.2% and 48.6%), the right to withdraw (76.5% and 43.2%) and the prospects of collective benefits (74.8% and 48.6%). By contrast, less than half of the parents and few of the children correctly understood the alternatives (respectively 47.5% and 27%), the risks related to participation (44.5% and 10.8%), the prospects of individual benefits (33.6% and 10.8%) and the purpose of the clinical trial (12.6% and 2.7%). Twenty-six (70.3%) children participated in the decision-making process. Most parents and children felt they had no choice but to participate in the trial to have access to a new anticancer treatment. CONCLUSIONS: What might appear to be a poor understanding of the research protocol may actually correspond to the families' interpretation of the situation as a coping mechanism. All children (except infants) should get age-tailored information in order for them to have a meaningful involvement in research.

COST-EFFECTIVENESS OF INTERVENTIONS BASED ON PHYSICAL ACTIVITY IN THE TREATMENT OF CHRONIC CONDITIONS: A SYSTEMATIC LITERATURE REVIEW.

OBJECTIVES: The aim of this study is to review evidence on the cost-effectiveness of exercise-based interventions in the treatment of chronic conditions a decade after the publication of Roine et al. in 2009 (Roine E, Roine RP, Räsänen P, et al. Int J Technol Assess Health Care. 2009;25:427-454). METHODS: We carried out a review of published articles in PUBMED and JSTOR between January 1, 2008, and December 31, 2016. Full economic evaluations of exercise programs targeting patients with a chronic condition were eligible for inclusion. Data on program, design, and economic characteristics were extracted using a predefined extraction form. The quality of the economic evaluations was appraised using the adjusted Consensus Health Economic Criteria List. RESULTS: A total of 426 articles were identified and thirty-seven studies were selected. Eleven studies dealt with musculoskeletal and rheumatologic disorders, ten with cardiovascular diseases, six with neurological disorders, three with mental illnesses, three with cancers, and four with diabetes, respiratory diseases, or pelvic organ prolapse. In total, 60 percent of exercise programs were dominant or cost-effective. For musculoskeletal and rheumatologic disorders, 72 percent of programs were dominant or cost-effective while this was the case for 57 percent of programs for cardiovascular diseases using a nonsurgical comparator. CONCLUSIONS: There is clear evidence in favor of exercise-based programs for the treatment of musculoskeletal and rheumatologic disorders and, to a lesser extent, for the treatment of cardiovascular diseases. More research is needed to evaluate the cost-effectiveness of physical activity in the treatment of neurological disorders, mental illnesses, cancers, respiratory diseases, and diabetes/obesity.

Historical perspective on neuroembryology: Wilhelm His and his contemporaries.

This year marks the 150th anniversary of the discovery of the neural crest by Wilhelm His (1831-1904). Beyond this discovery, His made possible the program of comparative anatomy at the cellular level thanks to the introduction in 1866 of the first microtome to have micrometer advance. His studies of the origin, migration, and fate of neural crest cells were foundational in the field of neuroembryology and contributed to the establishment of the neuron doctrine. The article places His' work in the scientific context of 19th century embryology, concerned with reconciling the embryonic layers theory, the cell theory and the evolution theory. From a methodological point of view, the article shows that His appears in this context at the junction of two embryological traditions, the descriptive morphological approach and the new experimental approach. The anatomical and physiological exploration of the neural crest and the controversies that followed highlight the transition between these two traditions that His enabled and of which he was one of the initiators.

Enrollment in early-phase clinical trials in pediatric oncology: The experience at Institut Curie.

BACKGROUND: The European Paediatric Regulation was introduced in 2007 to facilitate access to new medicines for children. Our study explored accessibility of early-phase trials in pediatric oncology, in line with the European Paediatric Regulation, to identify the reasons for not inviting patients to participate, parents' refusal, or inclusion failure. PROCEDURE: We conducted a retrospective chart review at Institut Curie, Paris, for all pediatric patients whose cancer progressed despite known effective treatments between July 2010 and December 2013. RESULTS: Out of 100 patients in the palliative phase, 52 received one or more invitations to participate in early-phase trials. Twenty parents declined the invitation, mainly prioritizing quality of life or fearing constraints. Fourteen inclusions failed despite parental approval, mostly due to rapid clinical deterioration. Five patients received no invitations because no early-phase trials were available. Major reasons for noninclusion in the 43 remaining patients were presence of exclusion criteria or other physical factors, preference for conventional treatment, constraints, psychological factors, and follow-up in another hospital after moving. CONCLUSIONS: The Paediatric Regulation has led to increased availability of early-phase trials. Better timing of the proposal, designing less constraining early-phase trials, reducing waiting lists, and improving information for parents and children would facilitate pediatric access to new medicines.

Wilhelm His and mechanistic approaches to development at the time of Entwicklungsmechanik.

At the end of the nineteenth century, approaches from experimental physiology made inroads into embryological research. A new generation of embryologists felt urged to study the mechanisms of organ formation. This new program, most prominently defended by Wilhelm Roux (1850-1924), was called Entwicklungsmechanik. Named variously as "causal embryology", "physiological embryology" or "developmental mechanics", it catalyzed the movement of embryology from a descriptive science to one exploring causal mechanisms. This article examines the specific scientific and epistemological meaning of the mechanistic approaches of embryological development by focusing on Wilhelm His' (1831-1904) histogenetic work. Roux was neither the first, nor the only one to argue for an experimental exploration of causes in embryology. At the time of Roux, physiological explanations of the genesis of the anatomical forms were developing in parallel, not only in German-speaking countries, but in France, Switzerland and English-speaking countries as well. The experimental approach and the cellular descriptions of embryogenesis were already omni-present when Roux proposed his Entwicklungsmechanik. However, these approaches remained disjointed. It appears that it was Wilhelm His who first succeeded in combining the question of the causal factors determining epigenesis, which was closely connected with experimentation on, and cellular descriptions of, development, in a coherent and concrete synthesis, making him one of the true initiators of the developmental mechanics.

Ethical issues of clinical trials in paediatric oncology from 2003 to 2013: a systematic review.

A state-of-the art approach to the debates on ethical issues is key in order to gain guidance on research practices involving sick children and adolescents, as well as to identify research avenues in which it might be worth cooperating, to generate better or supplementary evidence. Based on a systematic literature search using MEDLINE, we report the main ethical developments in paediatric oncology clinical trials from 2003-13. The present knowledge about normative and empirical ethical demands in this setting is quantified and summarised in a list of 46 issues. This list primarily aims to provide readers with a comprehensive account of the main decision nodes and professional attitudes that enable families to make a safe, competent, and satisfactory decision about their child's enrolment, or non-participation, in cancer clinical trials. Our systematic Review shows how important it is for professionals to engage in a constant reflection on optimum trial designs, on the effect of offering trial participation on key family dynamics, and on the ways to understand families' needs and values accurately. In view of present scientific developments, we further emphasise the need to enhance societal awareness about research in children and adolescents, to prevent so-called research fatigue in small populations due to multiple solicitations or inadequate legal demands, and to reassess longstanding ethical certainties in the strictest view of promoting sick children's interests. This systematic Review allows a series of questions to be drawn to guide and encourage collective and individual endeavours that should lead to constant improvements in our research practices in paediatric clinical oncology research.

[What to do with brain imaging? Old and new territories of a technology]. / Que faire de l'imagerie cérébrale ? Territoires anciens et nouveaux d'une technologie.

During the twentieth century, brain imaging revolutionized neurological practice and research in cognitive neuroscience. More recently, its scope has moved from the former territories to the humanities. After describing this historical dynamic, some issues and controversies related to old and new uses of neuroimaging are recalled, and this new appetite for brain image is questioned.

Some historical difficulties of the cholinergic transmission.

For a very long time, arguments supporting the neuro-humoral theory, produced by the pharmacologist Henri Dale, did not convince one of the main supporters of the electrical theory, the neurophysiologist John C. Eccles. This article gives a reminder of certain technical elements of this debate between two giants, which remains one of the most symbolic arguments in the history of neurosciences. The difficulties of the cholinergic transmission often betrayed the scepticism concerning the possibility of a functional approach based on neurochemistry.