Interaction between neonatal vitamin A supplementation and timing of measles vaccination: A retrospective analysis of three randomized trials from Guinea-Bissau

Background

In Guinea-Bissau we conducted three trials of neonatal vitamin A supplementation (NVAS) from 2002 to 2008. None of the trials found a beneficial effect on mortality. From 2003 to 2007, an early measles vaccine (MV) trial was ongoing, randomizing children 1:2 to early MV at 4.5 months or no early MV, in addition to the usual MV at 9 months. We have previously found interactions between vitamin A and vaccines.

Objective

We investigated whether there were interactions between NVAS and early MV.

Design

We compared the mortality of NVAS and placebo recipients: first, from 4.5 to 8 months for children randomized to early MV or no early MV; and second, from 9 to 17 months in children who had received two MV or one MV. Mortality rates (MR) were compared in Cox models producing mortality rate ratios (MRR).

Results

A total of 5141 children were randomized to NVAS (N = 3015) or placebo (N = 2126) and were later randomized to early MV (N = 1700) or no early MV (N = 3441). Between 4.5 and 8 months, NVAS compared with placebo was associated with higher mortality in early MV recipients (MR = 30 versus MR = 0, p = 0.01), but not in children who did not receive early MV (p for interaction between NVAS and early MV = 0.03). From 9 to 17 months NVAS was not associated with mortality. Overall, from 4.5 to 17 months NVAS was associated with increased mortality in early MV recipients (Mortality rate ratio = 5.39 (95% confidence interval: 1.62, 17.99)).

Conclusions

These observations indicate that NVAS may interact with vaccines given several months later. This may have implications for the planning of future child intervention programs.     

Single-dose varicella vaccine effectiveness in school settings in China

Background

Varicella vaccine has been available in the private sector in China for a decade as a single-dose regimen, but varicella vaccine effectiveness (VE) has not been fully examined in school settings yet.

Methods

A matched case–control study was carried out in elementary schools and daycares in Tai’an prefecture, Shandong province, China. Clinical diagnosis of varicella and breakthrough disease was used for this study. Four controls were randomly selected from classmates; two from classmates of the case and two from another class of the same grade without cases. Vaccination status, date of vaccination, and vaccine product received if vaccinated were collected from home and clinic immunization records. Vaccination status of all students in schools/daycares with varicella cases from home immunization records or parental recall was used to calculate vaccination coverage.

Results

The overall varicella VE was 83.4% (95% confidence interval 71.4–90.3%). Receipt of varicella vaccine five years or more years before the outbreak was significantly associated with breakthrough varicella (odds ratio = 4.7, P < 0.001), while age at vaccination (<15 vs. ≥15 months) was not (odds ratio = 1.5, P = 0.62). Varicella vaccination coverage was 41% with substantial variation across schools (range of 0–93.8%).

Conclusions

Single-dose varicella vaccine is highly effective in school settings. Maintaining limited vaccination coverage might shift varicella disease burden to older individuals, who are more prone to develop severe outcomes if varicella occurs.     

Neighborhood walkable urban form and C-reactive protein

Background

Walkable urban form predicts physical activity and lower body mass index, which lower C-reactive protein (CRP). However, urban form is also related to pollution, noise, social and health behavior, crowding, and other stressors, which may complement or contravene walkability effects.

Purpose

This paper assesses within-neighborhood correlation of CRP, and whether three features of walkable urban form (residential density, street connectivity, and land use mix) are associated with CRP levels.

Methods

CRP measures (n = 610) and sociodemographic data come from the 2001–3 Chicago Community Adult Health Study, linked with objective built environment data.

Results

Within-neighborhood correlations of CRP are greater than those of related health measures. A one standard deviation increase in residential density predicts significantly higher log CRP (e.g. β = 0.11, p < .01) in Chicago, while a one standard deviation increase in land use mix predicts significantly lower CRP (e.g. β = − 0. 19, p < 0.01). Street connectivity is unrelated to CRP in this highly walkable city.

Discussion

Results suggest that residential density may be a risk factor for inflammation, while greater walkability of mixed land use areas may be protective. It may be that negative aspects of density overcome the inflammatory benefits of walking.     

The effect of diabetes mellitus on immunological response to hepatitis B virus vaccine in individuals with chronic kidney disease: A meta-analysis of current literature

Background

Patients with chronic kidney disease (CKD) often fail to produce protective antibodies to hepatitis B virus (HBV) surface antigen after vaccination. Diabetes mellitus (DM) is the most common cause of CKD; however it is not clear whether it affects immunological response to HBV vaccine in these patients.

Aims

We aimed to evaluate the immunological response to HBV vaccine in diabetic patients with CKD by conducting a meta-analysis of the current literature.

Methods

Only studies that evaluated the seroprotection rate for diabetic against non-diabetic CKD patients or the immunological response of these groups to HBV vaccine were included. We applied the random effects model of DerSimonian and Laird, with heterogeneity (Q statistic), publication bias (Egger and Begg test) and sensitivity analyses. The rate of patients showing seroprotective anti-HBsAg titers (>10 IU/mL) at completion of HBV vaccination schedule in the diabetic versus the non-diabetic CKD patients was set as our end-point of interest.

Results

We identified seven studies that fulfilled our inclusion criteria involving 15,073 unique patients with CKD. Aggregation of study results showed a significant decrease in response rates among the diabetic versus the non-diabetic patients [pooled odds ratio = 0.58 (95% CI 0.37–0.89), Q(6) = 11.3, I² = 50%]. The P-value was 0.07 for our test of heterogeneity.

Conclusions

Our meta-analysis determined that HBV vaccination's seroprotection rate in diabetic CKD patients is significantly lower than that in non-diabetic CKD patients. Therefore, using vaccine adjuvants such as oral levamisole, granulocyte macrophage-colony stimulating factor or intradermal injection might be advisable in these patients.     

Personal attitudes and misconceptions,not official recommendations guide occupational physicians’ vaccination decisions

Introduction

Healthcare personnel (HCP) are often under-vaccinated. The aim of this study was to evaluate occupational physicians’ potential role by assessing relations between their knowledge and attitudes regarding HCP vaccination and the extent to which official vaccination recommendations are communicated.

Methods

Cross-sectional survey, n = 135 occupational physicians.

Results

Occupational physicians who treat HCP recommend vaccinations more often to HCP when they have better knowledge of official vaccination recommendations and a more positive attitude towards vaccination compared to physicians with less such knowledge or a more negative attitude. The attitude towards vaccination most strongly affects whether occupational physicians recommend the measles, mumps, and rubella (MMR) vaccination: physicians with less positive attitudes recommend MMR to HCP in a more restricted way. A more positive attitude towards vaccination also relates to fewer misconceptions. Occupational physicians’ knowledge and attitude further influence the extent to which pregnant HCP receive vaccinations against influenza. Knowledge about official recommendations does not influence the recommendation of influenza vaccination for pregnant women.

Conclusions

Reasons for vaccination gaps in HCP might have their roots in occupational physicians’ incomplete knowledge of vaccination recommendations. Attitudes, which are related to misperceptions, also influence which vaccinations are recommended to HCP. Official recommendations, and not personal attitudes and misconceptions, should guide occupational vaccination behavior.     

Perspectives of physicians practicing in low and middle income countries towards generic medicines: A narrative review

Objectives

This review was conducted to document published literature related to physicians’ knowledge, attitudes, and perceptions of generic medicines in low- and middle-income countries (LMICs) and to compare the findings with high-income countries.

Methods

A systematic search of articles published in peer-reviewed journals from January 2001 to February 2013 was performed. The search comprised nine electronic databases. The search strategy involved using Boolean operators for combinations of the following terms: generic medicines, generic medications, generic drugs, generic, generic substitution, generic prescribing, international non-proprietary, prescribers, doctors, general practitioners, physicians, and specialists.

Results

Sixteen articles were included in this review. The majority (n = 11) were from high income countries and five from LMICs. The main difference between high income countries and LMICs is that physicians from high income countries generally have positive views whereas those from LMICs tend to have mixed views regarding generic medicines. Few similarities were identified among different country income groups namely low level of physicians’ knowledge of the basis of bioequivalence testing, cost of generic medicines as an encouraging factor for generic medicine prescribing, physicians’ concerns towards safety and quality of generic medicines and effect of pharmaceutical sales representative on generic medicine prescribing.

Conclusion

The present literature review revealed that physicians from LMICs tend to have mixed views regarding generic medicines. This may be due to differences in the health care system and pharmaceutical funding system, medicine policies, the level of educational interventions, and drug information sources in countries of different income levels.     

Intimate partner violence in Europe: design and methods of a multinational study

Objective

To describe the design, methods, procedures and characteristics of the population involved in a study designed to compare Intimate Partner Violence (IPV) in eight European countries.

Methods

Women and men aged 18–65, living in Ghent-Belgium (n = 245), Stuttgart-Germany (n = 546), Athens-Greece (n = 548), Budapest-Hungary (n = 604), Porto-Portugal (n = 635), Granada-Spain (n = 138), Östersund-Sweden (n = 592), London-United Kingdom (n = 571), were sampled and administered a common questionnaire. Chi-square goodness of fit and five-age strata population fractions ratios for sex and education were computed to evaluate samples’ representativeness.

Results

Differences in the age distributions were found among women from Sweden and Portugal and among men from Belgium, Hungary, Portugal and Sweden. Over-recruitment of more educated respondents was noted in all sites.

Conclusion

The use of a common research protocol with the same structured questionnaire is likely to provide accurate estimates of the general population IPV frequency, despite limitations in probabilistic sampling and restrictions in methods of administration.     

Integrating family planning and prevention of mother to child HIV transmission in Zimbabwe

Objective

The objective was to integrate enhanced family planning (FP) and prevention of mother-to-child HIV transmission services in order to help HIV-positive Zimbabwean women achieve their desired family size and spacing as well as to maximize maternal and child health.

Study Design

HIV-positive pregnant women were enrolled into a standard-of-care (SOC, n= 33) or intervention (n= 65) cohort, based on study entry date, and followed for 3 months postpartum. The intervention cohort received education sessions aimed at increasing FP use and negotiation power. Both groups received care from nurses with enhanced FP training. Outcomes included FP use, FP knowledge and HIV disclosure, and were assessed with Fisher’s Exact Tests, binomial tests and t tests.

Results

The intervention cohort reported increased control over condom use (p=.002), increased knowledge about IUDs (p=.002), increased relationship power (p=.01) and increased likelihood of disclosing their HIV status to a partner (p=.04) and having that partner disclose to them (p=.04) when compared to the SOC cohort. Long-acting reversible contraception (LARC) use in both groups increased from ~ 2% at baseline to > 80% at 3 months postpartum (p<.001).

Conclusions

FP and sexual negotiation skills and knowledge, as well as HIV disclosure, increased significantly in the intervention cohort. LARC uptake increased significantly in both the intervention and SOC cohorts, likely because both groups received care from nurses with enhanced FP training. Successful service integration models are needed to maximize health outcomes in resource-constrained environments; this intervention is such a model that should be replicable in other settings in sub-Saharan Africa and beyond.

Implications

This study provides a rigorously evaluated intervention to integrate FP education into ante- and postnatal care for HIV-positive women and also to train providers on FP. Results suggest that this intervention had significant effects on contraception use and communication with sexual partners. This intervention should be adaptable to other areas.     

Multiple chemical sensitivity: On the scent of central sensitization

Background

Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by recurrent, non-specific symptoms in response to chemically unrelated exposures in non-toxic concentrations. Although the pathophysiology of MCS remains unknown, central sensitization may be an important factor contributing to the clinical manifestations.

Purpose

To use quantitative sensory testing (QST) to study central hyperexcitability and multiple aspects of central sensory processing in MCS patients without comorbid overlapping disorders and to compare the results with those among matched controls.

Methods

15 MCS patients and 15 healthy matched controls underwent QST to assess the following aspects of pain: capsaicin-induced secondary punctate hyperalgesia, stimulus response function (SRF) to punctate mechanical stimuli before and after capsaicin injection, temporal summation to punctate stimuli post capsaicin injection, pressure pain thresholds, heat pain thresholds, tonic heat stimulation and conditioning pain modulation (CPM: formerly known as diffuse noxious inhibitory control or DNIC).

Results

The mean area of capsaicin-induced secondary punctate hyperalgesia was significantly larger in MCS patients than in controls at 5, 30 and 60 min post capsaicin injection (p = 0.01). In addition MCS patients reported higher ratings in response to punctate mechanical stimuli assessed by SRF compared with controls (p < 0.001). The CPM test induced significantly higher pain ratings in patients than in controls (p = 0.002). We found no group differences in pressure pain and heat pain thresholds, temporal summation to punctate stimuli post capsaicin injection, capsaicin and tonic heat pain ratings or CPM effect.

Conclusion

Increased capsaicin-induced secondary punctate hyperalgesia was demonstrated in MCS patients without comorbid, overlapping disorders, suggesting facilitated central sensitization in MCS.     

Evaluating the impact of pluridisciplinary training on proper glove use in hospital

Objective

The authors of this randomized study had for aim to evaluate the impact of training on proper glove use by comparing compliance to glove use recommendations between trained and untrained healthcare personnel according to healthcare professional groups.

Patients and methods

A random selection of trained and untrained nurses, nurse aids, and hospital housekeepers was performed in a French University hospital, using a listing of healthcare personnel. The audits were conducted by two infection control nurses, in series of 10 observations, with a maximum time limit of two hours. The evaluation criteria were compliance or non-compliance of glove-wearing practices with internal hospital recommendations, disclosed to professionals during training.

Results

Overall, 111 professionals were audited and 794 acts were observed. Hand hygiene was significantly better in trained vs. untrained healthcare professionals (P < 0.01). Proper glove use practices were similar between trained and untrained nurses (85% of compliance), whereas the difference was statistically significant in favor of trained healthcare personnel for the other categories (P < 0.001 for nurse aids and P = 0.02 for housekeepers).

Conclusion

We demonstrated the impact of pluridisciplinary training on proper glove use practices in hospital settings, but with different benefits found according to professional groups. The lower the initial training level, the greater the overall benefit appeared to be.     

A randomized trial of calorie labeling on menus

Background

Food consumed outside the home accounts for a growing proportion of the North American diet and has been associated with increased obesity.

Purpose

To examine the effect of nutrition labeling on menus on awareness, use, and food consumption, including the impact of “traffic light” labeling and adding other nutrients.

Methods

Blinded, randomized trial with 635 Canadian adults conducted in 2010–2011. Participants ordered a free meal from one of four experimental menus: 1) no nutritional information shown, 2) calorie amounts only, 3) calorie amounts in “traffic lights”, and 4) calorie, fat, sodium, and sugar shown in “traffic lights”. Recall of nutrition information, knowledge of calorie content and nutrient consumption were assessed.

Results

Participants in the calorie conditions were more likely to recall the calorie content of meals and to report using nutrition information when ordering. The calorie content of meals was not significantly different across conditions; however, calorie consumption was significantly lower among participants in the Calorie-only condition compared to the No information condition (mean = − 96 kcal, p = .048).

Conclusions

Menu labeling increased awareness and use of nutrition information and reduced consumption. Adding “traffic lights”, fat, sodium, and sugar amounts to menus had little impact compared to calorie-only labeling.     

Population-level evaluation of school-based interventions to prevent problem substance use among gay,lesbian and bisexual adolescents in Canada

Objective

This study examined whether students' odds of recent substance use were lower in the presence of gay-straight alliances or explicit anti-homophobia policy that had been established at their school recently, or at least 3 years prior.

Methods

We analyzed a population-based sample of students in grades 8 through 12 from the British Columbia Adolescent Health Survey of 2008 (weighted N = 21,708). We used multi-nomial logistic regressions to test the hypothesized effects of gay-straight alliances and policies on substance use outcomes for lesbian, gay and bisexual students, and heterosexual students separately.

Results

Results indicated that gay-straight alliances and anti-homophobic bullying policies were linked to significantly lower odds of some but not all types of recent risky alcohol use, and past-year harms from alcohol or drug use, but almost exclusively in schools where the policies or gay-straight alliances had been established for at least 3 years; and among lesbian, gay and bisexual adolescents, only for girls.

Conclusions

Our findings suggest that these school-based strategies (gay-straight alliances and anti-homophobia policies) to reduce homophobia and foster school inclusion may be beneficial in reducing problem alcohol use among all students, not just sexual minority students.     

Knowledge,attitudes and vaccination coverage of healthcare workers regarding occupational vaccinations

Objectives

Immunization of healthcare workers (HCWs) is a major issue for infection control in healthcare facilities. The aim of this study was to evaluate knowledge regarding occupational vaccinations, HBV, varicella and influenza vaccination rates and attitudes towards influenza vaccine among HCWs.

Design and setting

A cross-sectional survey was conducted in two wards (Medicine and Paediatrics) of a 1182-bed teaching hospital in Paris, France.

Methods

A standardized, anonymous, self-administered questionnaire was used.

Results

Of 580 HCWs, 395 (68%) completed the questionnaire. Knowledge about the occupational vaccinations of HCWs was low. HBV (69%), tuberculosis (54%) and influenza (52%) were the most cited vaccinations. Paediatric staff was more aware of influenza and pertussis immunizations (p < .05). HBV vaccination rate was 93%, among whom 65% were aware of their immune status. Influenza vaccination rate for 2006–2007 was 30% overall, ranging from 50% among physicians to 20% among paramedical staff (p < .05). Physicians based their refusal on doubts about vaccine efficacy, although paramedics feared side effects. Influenza vaccination was associated with knowledge of vaccine recommendations [OR = 1.75, 95% CI: 1.13–2.57] and contact with patients [OR = 3.05, 95% CI: 1.50–5.91].

Conclusions

Knowledge of recommended occupational vaccinations is insufficient in HCWs, except for HBV and influenza. Although the HBV vaccine coverage of HCWs is satisfactory, a large proportion of them is unaware of immune status. Influenza vaccine coverage remains low, especially among paramedical staff because of fear of side effects. As vaccine coverage is associated with knowledge, educational campaigns should be strengthened to increase the adhesion of HCWs to vaccinations.     

Méthode d’évaluation des pratiques professionnelles (EPP) au cours de l’antibiothérapie des pneumopathies aiguës communautaires

Introduction

Methods used for the assessment of professional practices must be dependable and reproducible. The aim of this study was to assess a method used in our hospital to assess antibiotic therapy for acute community-acquired pneumonia (CAP).

Method

In this study, a pharmacist and two infectious disease specialists retrospectively and independently evaluated the compliance to local antibiotic guidelines for 124 patients. The assessment tool was a Medical Appropriateness Index (MAI) (nine items). The kappa agreement index (K) among experts was calculated.

Results

The agreement among experts was poor for the initial antibiotic treatment (K = 0.16) and route of administration (K = 0.14), low for the duration of treatment (K = 0.34), and null for the dose and adjustment to 72 hours.

Conclusion

Differences between experts can be explained by the complexity of medical records, the number of items assessed, the complexity of the MAI, but also by the specialization and experience of experts. Thus, the assessment of CAP antibiotic therapy requires the use of appropriate methods targeting reliable criteria.     

Impact on disease incidence of a routine universal and catch-up vaccination strategy against Neisseria meningitidis C in Tuscany,Italy

Background

Invasive infections due to Neisseria meningitidis are still an important public health issue worldwide. In Europe, meningococcal meningitis is differently distributed in the EU countries, but most cases of meningococcal diseases are caused by serogroups B and C. In Italy, each year about 900 cases of bacterial meningitis occur, of whom one third are caused by N. meningitidis. In March 2005, the Regional Health Authority of Tuscany approved a policy of active offer of conjugate meningococcus C (MCC) vaccination with three doses to all newborns at 3, 5 and 13 months of age (subsequently turning to a single dose at 13 months as of 2008) and a catch-up until age 6 years with a single dose.

Objective

The aim of the present study was to evaluate the effectiveness of the vaccination strategy adopted by Tuscany in preventing cases of invasive meningococcal C disease.

Methods

Surveillance data for the calculation of disease incidence, immunization coverage with MCC vaccine and vaccination status of meningitis cases were collected from 2005 to 2011.

Results

Incidence rates of meningococcal meningitis and septicemia decreased in all age groups involved in the immunization campaign, as a result of the progressively increasing vaccination coverage. Since 2006, no cases of invasive meningococcal C infection in vaccinated subjects were observed in Tuscany. A herd immunity effect was measured in unvaccinated age groups.

Conclusion

MCC vaccination implementation in Tuscany was successful in the prevention of meningococcal C disease. Our results should prompt all Italian Regions to consider introducing MCC vaccination in order to protect their population.     

A cluster randomized controlled trial of strategies to increase adolescents' physical activity and motivation in physical education: Results of the Motivating Active Learning in Physical Education (MALP) trial

Objective

Physical education (PE) programs aim to promote physical activity (PA) and reach most school-aged youth. However, PA levels within PE lessons are often low. In this cluster-randomized controlled trial, we examined the effects of three self-determination theory-based motivational strategies on PA and sedentary behavior, as well as their hypothesized antecedents during PE lessons.

Methods

Data were collected in Sydney, Australia (October–December 2011). After baseline testing, teachers (n = 16) and their classes (n = 288 students; M = 13.6 years, 50.4% male) were randomly assigned to one of four teaching strategy conditions: (1) explaining relevance; (2) providing choice; (3) complete free choice; or (4) usual practice. Teachers then delivered the assigned strategy. Primary outcomes were accelerometer-assessed PA and student motivation during lessons. Secondary outcomes included sedentary behavior, perceptions of teachers' support and psychological needs satisfaction.

Results

The ‘free choice’ intervention increased PA (p < .05). ‘Providing choice’ and ‘free choice’ interventions decreased sedentary behavior (p < .05). The interventions did not influence motivation, but students' autonomy increased during both choice-based interventions (p < .05).

Conclusions

Promoting choice can produce short-term increases in PA and decreases in sedentary behavior, as well as increased perceived autonomy during PE lessons.     

Safety and immunogenicity of a pneumococcal histidine triad protein D vaccine candidate in adults

Background

Pneumococcal vaccines based on conserved protein antigens have the potential to offer expanded protection against Streptococcus pneumoniae.

Objective

To explore safety and immunogenicity of a recombinant protein vaccine candidate against S. pneumoniae composed of adjuvanted pneumococcal histidine triad protein D (PhtD).

Methods

This phase I, exploratory, open-label, single-center clinical study enrolled adults (18–50 years). Participants in a pilot safety cohort received a single intramuscular injection of 6 μg. Following safety review, 3 dose cohorts were enrolled (6, 25, and 100 μg); participants received 2 injections administered approximately 30 days apart. Assignment of the second injection and successive dose cohorts were made after blinded safety reviews after each injection at each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events, serious adverse events, and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD antibodies as measured by ELISA.

Results

Sixty-three participants were enrolled and received the pilot safety dose (n = 3) or at least 1 dose of PhtD vaccine candidate at 6 μg (n = 20), 25 μg (n = 20), or 100 μg (n = 20). No safety concerns were identified. No vaccine-related serious adverse event was reported. The most common solicited injection site reaction was pain and most common solicited systemic reactions were myalgia and headache; most reactions were mild and transient. Observed geometric mean concentrations (95% CI) were 200.99 ELISA units (148.46, 272.10), 352.07 (193.49, 640.63), and 699.15 (405.49, 1205.48) post-injection 1 in the 6, 25, and 100 μg dose cohorts, respectively, and 378.25 (275.56, 519.21), 837.32 (539.29, 1300.04), and 1568.62 (1082.92, 2272.16) post-injection 2.

Conclusions

All dose levels were safe and immunogenic. The frequency of solicited reactions was highest at the 100 μg dose. Administration of a second injection significantly increased the levels of anti-PhtD antibodies (ClinicalTrials.gov registry no. NCT01444001).     

Do reassessments reduce the uncertainty of decision making? Reviewing reimbursement reports and economic evaluations of three expensive drugs over time

Objective

To investigate the desirability and feasibility of a cyclic reimbursement process to address uncertainty accompanying initial decision making.

Methods

We performed desk research for three expensive outpatient drugs: imatinib, pegfilgrastim, and adalimumab. We analysed the evidence base at the time of decision making (T = 0) and May 2011 (T = 1). For T = 0, public reports of the Dutch reimbursement agency were investigated regarding available clinical and economic evidence, and a systematic review was performed to retrieve additional economic evidence. For T = 1, the systematic review was extended till May 2011.

Results

The evidence base at T = 0 lacked information on clinically relevant outcomes such as mortality, morbidity, and quality of life (5/8 reports), (long-term) adverse events (2/8 reports) and experience in use (1/8 reports). One budget impact analysis and one economic evaluation were available but no pharmacoeconomic dossiers. The systematic review identified 39 cost-utility studies (of 52 economic evaluations) for T = 1, characterised by methodological heterogeneity.

Conclusions

Given the considerable uncertainty accompanying initial decision-making, a more cyclic reimbursement process seems feasible to reduce uncertainty regarding the therapeutical and economical value of expensive drugs. A mandatory evidence development requirement seems desirable to sufficiently meet decision makers’ needs.