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Implicit factors can be defined as any criteria that play a role in the health technology assessment (HTA) deliberative process but are not part of the HTA framework. To date, very few studies have explored the influence of implicit factors on this process. This survey of HTA experts in five European countries aimed to analyze the influence of implicit factors on the HTA deliberative process.
Semi-structured interviews with 20 HTA experts from five European countries (France, Germany, Italy, Spain, and the United Kingdom) were conducted from February to May 2021. The main topics of the interviews were: the HTA deliberative process; the degree of influence on the HTA deliberative process of a set of factors previously identified in a systematic literature review performed by the authors; and recommendations for improving the deliberative process.
All but two of the experts concurred that implicit factors played a role in the deliberative process. German experts considered that the factors explored had a low influence on the process. Burden of disease and unmet need scored highest, followed by the professional experience of the people involved in the HTA deliberative process. To improve the deliberative process, experts suggested expanding the external stakeholder perspective (i.e., including patients, the pharmaceutical industry, and the public), increasing transparency when revealing implicit factors, and implementing a methodology to mitigate the influence of implicit factors.
Our survey indicates a need to increase external involvement in the process and to develop a methodology for unmasking the implicit factors in the deliberative process. This may be achieved by either updating the current frameworks to include these implicit factors or by developing new methods to address them. Further research may explore approaches to acknowledge the implicit factors in the HTA deliberative process in a systematic manner.
This review intends to provide an overview of revealed preferences of decision-makers for recommendations of cancer drugs in health technology assessment (HTA) among the different agencies.
A systematic literature search was performed in MEDLINE and EMBASE databases from inception to July 2020. The studies were eligible for inclusion if they conducted a quantitative analysis of HTA’s previous decisions for cancer drugs. The factors with p-values below the significance level of .05 were considered as the statistically significant factors for HTA decisions.
A total of nine studies for six agencies in Australia, Belgium, France, South Korea, the UK, and Canada were eligible to be included. From the univariable analysis, improvements in clinical outcomes and cost-effectiveness were found as significant factors for the agencies in Belgium, South Korea, and Canada. From the multivariable analysis, cost-effectiveness was found as a positive factor for the agencies in the UK, South Korea, and Canada. Few factors related to characteristics of disease and technology were found to be significant among the included agencies.
Despite the different drug reimbursement systems and the socioeconomic situations, cost-effectiveness and/or improvement on clinical outcomes seemed to be the most important factors for recommendations of cancer drugs among the agencies.
Recent network models propose that mutual interaction between symptoms has an important bearing on the onset of schizophrenic disorder. In particular, cross-sectional studies suggest that affective symptoms may influence the emergence of psychotic symptoms. However, longitudinal analysis offers a more compelling test for causation: the European Schizophrenia Cohort (EuroSC) provides data suitable for this purpose. We predicted that the persistence of psychotic symptoms would be driven by the continuing presence of affective disturbance.
EuroSC included 1208 patients randomly sampled from outpatient services in France, Germany and the UK. Initial measures of psychotic and affective symptoms were repeated four times at 6-month intervals, thereby furnishing five time-points. To examine interactions between symptoms both within and between time-slices, we adopted a novel technique for modelling longitudinal data in psychiatry. This was a form of Bayesian network analysis that involved learning dynamic directed acyclic graphs (DAGs).
Our DAG analysis suggests that the main drivers of symptoms in this long-term sample were delusions and paranoid thinking. These led to affective disturbance, not vice versa as we initially predicted. The enduring relationship between symptoms was unaffected by whether patients were receiving first- or second-generation antipsychotic medication.
In this cohort of people with chronic schizophrenia treated with medication, symptoms were essentially stable over long periods. However, affective symptoms appeared driven by the persistence of delusions and persecutory thinking, a finding not previously reported. Although our findings as ever remain hostage to unmeasured confounders, these enduring psychotic symptoms might nevertheless be appropriate candidates for directly targeted psychological interventions.
To quantify and compare the resource consumption and direct costs of medical mental health care of patients suffering from schizophrenia in France, Germany and the United Kingdom.
In the European Cohort Study of Schizophrenia, a naturalistic two-year follow-up study, patients were recruited in France (N = 288), Germany (N = 618), and the United Kingdom (N = 302). Data about the use of services and medication were collected. Unit cost data were obtained and transformed into United States Dollar Purchasing Power Parities (USD-PPP). Mean service use and costs were estimated using between-effects regression models.
In the French/German/UK sample estimated means for a six-month period were respectively 5.7, 7.5 and 6.4 inpatient days, and 11.0, 1.3, and 0.7 day-clinic days. After controlling for age, sex, number of former hospitalizations and psychopathology (CGI score), mean costs were 3700/2815/3352 USD-PPP.
Service use and estimated costs varied considerably between countries. The greatest differences were related to day-clinic use. The use of services was not consistently higher in one country than in the others. Estimated costs did not necessarily reflect the quantity of service use, since unit costs for individual types of service varied considerably between countries.
The interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms.
We analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months.
We found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct.
Our findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.
Re-purposing of established products (EPs) – defined as marketed for 8 years or more – may represent a high value for patients and society. It has been recognized by the European Commission as an important factor contributing to greater access to new therapies. Due to a lower development cost, it could also represent a cost-effective alternative and help to reduce pressure on healthcare budgets. However, it is perceived that no financial incentives exist for the pharmaceutical industry to invest in new indications for EPs. The objective of this research was to review current European regulations and propose strategies stimulating development in this field.
We performed a targeted literature review and held two international expert panel workshops to discuss current policies and their implications, and issue recommendations for changes.
Within the current regulatory framework EPs face price cuts due to generic competition, reference pricing (RP), price re-negotiations or systematic price cuts, after a period of marketing presence. Extension of indications does not permit to increase or maintain the price. Generic substitution regardless of indication poses another challenge. Limited incentives in the form of an additional year of market protection exists only for new indication(s) registered within the first 8 years following initial approval. The expert panel proposed several strategies to stimulate development in this field, including: (i) extending the period in which registering a new indication results in additional market protection beyond 8 years and extending the duration of additional market protection; (ii) delaying inclusion in RP for EPs with a new value adding indication; (iii) establishing a differential pricing by indication; (iv) preventing temporarily generic substitution when an EP is prescribed for a new indication.
Current regulations represent a serious disincentive to develop new indications for EPs. Regulatory and pricing policy changes are needed to stimulate development in this important field.
Value added medicines (VAM) are medicines based on known molecules that address healthcare needs and deliver relevant improvements for patients, healthcare professionals and/or payers through drug repositioning, drug reformulation or drug combination (1-3). Recently, the European Commission, through the Safe and Timely Access to Medicines for Patients (STAMP) program, considered the issue of VAM development and regulatory process. Current Health Technology Assessment (HTA) tools may not fully capture the benefits of VAM, which could lead to obstacles for patient access to VAM in several European countries (1). The study objective was to identify how HTA frameworks should evolve to reflect VAM value.
HTA expert interviews were performed as a preparatory step to an advisory board meeting. The following topics were addressed: (i) Eligibility for HTA and early HTA dialogues; (ii) Attributes that should be considered in HTA; (iii) HTA methodology; and (iv) Involvement of stakeholders in HTA.
VAMs bring additional benefit to patients and society. Therefore, the possibility for VAM assessment on a voluntary basis and within the appropriate assessment patterns/tools should be, in principle, included into HTA frameworks, as well as into early HTA dialogues. HTA should be patient-centric, and attributes such as patient preference, adherence, and patient reported outcomes should be considered where relevant. Unmet patient needs and disease burden should be used in a transparent and reproducible deliberative process. All these attributes should be used as explicitly and meaningfully weighted appraisal modifiers. HTA methodology should be comprehensive and should integrate societal perspectives. Patient representatives should take part in the decision-making process.
Current HTA frameworks should evolve to enhance VAM value recognition and encourage industry investment in medicines with high potential value for society.
Exploring cultural differences may improve understanding about the social processes underlying the stigmatisation of people with mental illness.
To compare public beliefs and attitudes about schizophrenia in Central Europe and North Africa.
Representative national population surveys conducted in Germany (2011) and in Tunisia (2012), using the same interview mode (face to face) and the same fully structured interview.
In Tunisia, respondents showed a stronger tendency to hold the person with schizophrenia responsible for the condition. At the same time they expressed more prosocial reactions and less fear than their German counterparts. In Germany, the desire for social distance was greater for more distant relationships, whereas in Tunisia this was the case for close, family-related relationships.
Stigma differs between Tunisia and Germany more in form than in magnitude. It manifests particularly in those social roles which ‘matter most’ to people within a given culture.
Aim – To examine the associations of job acquisition and loss in a representative, prospective community sample of people with schizophrenia living in the UK, France and Germany. Method – A representative sample of twelve hundred and eight people with schizophrenia were recruited from selected secondary mental health services in the U.K, France and Germany and followed up for 2 years. Information on demographic details, psychotic symptoms and work status was collected. Results – The odds of getting jobs were increased by being resident in Marseille, Leipzig, Hemer and Heilbronn and by a higher regional general population employment rate. The odds were reduced by living in Lyon, a later illness onset, a longer length of illness, a continuous illness course and more severe negative psychotic symptoms. Previous vocational training reduced the odds of losing employment, whilst living in Lyon or Leipzig, harmful use of alcohol and more positive psychotic symptoms at baseline all increased the odds. Conclusions – In addition to illness related factors, area of residence and local labour market conditions appear to be important in explaining employment status change in people with schizophrenia.
Declaration of Interest: All authors declare there are no conflicts of interest. This study was funded by grants from Lundbeck A/S and from the German Federal Ministry of Education and Research.
Little is known about international variations in employment rates among people with schizophrenia or about the factors associated with employment in this disorder.
To describe employment patterns and the variables associated with working in an international sample of people with schizophrenia.
An analysis was made of baseline data from the European Schizophrenia Cohort study, a 2-year investigation of people with schizophrenia in contact with secondary services and living in France, Germany and the UK (n = 1208).
Participants were working in all sections of the job market. People who had a degree, were living with their families or had experienced only a single episode of illness were more likely to be working. A continuous illness course, more severe non-psychotic symptoms and drug misuse reduced the odds of employment. There were large variations between centres in employment rates, which were highest in the three German study sites. These differences persisted after adjustment for individual characteristics.
Local social contexts may be as important as individual or illness-related factors in explaining employment status.
Burden on the relatives of patients with schizophrenia may be influenced not only by patient and caregiver characteristics, but also by differences in mental health service provision.
To analyse whether family burden is affected by national differences in the provision of mental health services.
Patients with schizophrenia and their key relatives were examined in Germany (n=333) and Britain (n = 170). Differences in family burden in both countries were analysed with regression models controlling for patient and caregiver characteristics.
Family burden was associated with patients' symptoms, male gender, unemployment and marital status, as well as caregivers' coping abilities, patient contact and being a patient's parent. However, even when these attributes were controlled for, British caregivers reported more burden than German caregivers.
National differences in family burden may be related to different healthcare systems in Germany and Britain. Support for patients with schizophrenia may be shifted from the professional to the informal healthcare sector more in Britain than in Germany.
Relapse is one of the most costly aspects of schizophrenia.
To compare costs, clinical outcomes and quality of life for patients who experienced relapse in schizophrenia with a control group who did not relapse.
Patients were randomly selected from current psychiatric case-loads drawn from urban and suburban areas of Leicester. Differences in costs and outcomes by relapse status in the previous 6 months were examined using parametric and non-parametric tests, and multivariate analysis was used to examine factors associated with relapse and costs.
Costs for the patients who relapsed were over four times higher than those for the non-relapse group. There were few statistically significant differences in clinical and quality of life measures by relapse status. Multivariate analyses suggested some significant correlates of relapse and costs.
The higher costs associated with relapse will be of interest to policy-makers who face difficult choices concerning new but more expensive treatments for patients with schizophrenia.
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