EVITA: a tool for the early evaluation of pharmaceutical innovations with regard to therapeutic advantage.

BACKGROUND: New drugs are generally claimed to represent a therapeutic innovation. However, scientific evidence of a substantial clinical advantage is often lacking. This may be the result of using inadequate control groups or surrogate outcomes only in the clinical trials. In view of this, EVITA was developed as a user-friendly transparent tool for the early evaluation of the additional therapeutic value of a new drug. METHODS: EVITA does not evaluate a new compound per se but in an approved indication in comparison with existing therapeutic strategies. Placebo as a comparator is accepted only in the absence of an established therapy or if employed in an add-on strategy on top. The evaluation attributes rating points to the drug in question, taking into consideration both therapeutic benefit and risk profile. The compound scores positive points for superiority in efficiency and/or adverse effects as demonstrated in randomized controlled trials (RCTs), whilst negative points are awarded for inferiority and/or an unfavorable risk profile. The evaluation follows an algorithm considering the clinical relevance of the outcomes, the strength of the therapeutic effect and the number of RCTs performed. Categories for therapeutic aim and disease severity, although essential parts of the EVITA assessment, are attributed but do not influence the EVITA score which is presented as a color-coded bar graph. In case the available data were unsuitable for an EVITA calculation, a traffic-type yield sign is assigned instead to criticize such practice. The results are presented online http://www.evita-report.de together with all RCTs considered as well as the reasons for excluding a given RCT from the evaluation. This allows for immediate revision in response to justified criticism and simplifies the inclusion of new data. RESULTS: As examples, four compounds which received approval within the last years were evaluated for one of their clinical indications: lenalidomide, pioglitazone, bupropion and zoledronic acid. Only the first achieved an EVITA score above zero indicating therapeutic advantage. CONCLUSIONS: The strength of EVITA appears to lie in its speedy assessment of the potential therapeutic advantage of a new drug for a given indication. At the same time, this approach draws attention to the typical deficits of data used for drug approval. EVITA is not intended to replace classical health technology assessment reports but rather serves as a screening tool in the sense of horizon scanning.

Private and public willingness to pay for safety: A validity test.

Stated preference (SP) methods are often used to elicit an affected population's preferences for, e.g., increased safety or better environmental quality. SP methods are based on hypothetical market scenarios which have advantages, since decision alternatives are known to the analysis, but also necessitate thorough validity tests of the results, since decisions are hypothetical. This study suggests a validity test based on theoretical predictions and empirical findings for private and public safety measures. According to the test, willingness to pay (WTP) for a public safety measure should exceed or be equal to the private one. Based on a rich data set eliciting both private and public WTP the results show that private WTP exceeds public WTP. Hence, the findings in this study highlight the importance of validity tests of preference estimates for safety, and suggest that WTP also for a private safety measure should be elicited in studies eliciting WTP for public safety measures, to allow for the validity test.

Resialylation of sialic acid deficit vascular endothelium, circulating cells and macromolecules may counteract the development of atherosclerosis: a hypothesis.

Deficit sialylation of vascular endothelium, circulating cells and macromolecules has been associated with the development of atherosclerosis. On the other hand, an elevated serum level of sialic acid is a long-lasting marker of atherosclerosis and complications from atherosclerosis. One may speculate that the inverse associations with atherosclerosis risk are due to some common underlying cause. One mission for the elevated serum sialic acid level might be to act as a substrate for resialylation of sialic acid deficit structures and thereby counteract the atherosclerotic process.

Can drug treatment prevent disease in common practice?

To assess whether drug treatment in common practice can prevent disease, we analysed four preventive cardiovascular randomised clinical trials (RCTs), expressing efficacy by 1-year Number Needed to Treat (NNT) in RCT and common practice effectiveness by the Disease Impact Number (DIN) in all subjects at risk and by the Population impact Number (PIN) in the entire population, based on a Swedish population survey. Adjustments were made for non-adherence. Calculations were made of alternative 1-year drug costs and number of years an average general practitioner (GP) would need to work in order to prevent one event using the actual treatment. Secondary prevention of MI by simvastatin (NNT, DIN and adjusted PIN = 37, 93 and 2657; GP work time 2.7 years; drug costs Euro 1020 - 13505), and prevention of stroke by antihypertensive treatment in high-risk subjects (elderly with systolic blood pressure > 160 mm Hg; NNT, DIN and adjusted PIN = 167, 239 and 11950; GP work time 6 years; drug costs Euro 6095 - 51567) appeared medically and economically effective. Primary prevention of MI by pravastatin (NNT, DIN and adjusted PIN 208, 2080 and 24470; GP work time 12.2 years; drug costs Euro 5736 - 117676) or by antihypertensive drug treatment in low-risk subjects (diastolic blood pressure 90-99 mm Hg) (NNT, DIN and adjusted PIN 1667, 3334 and 116982; GP work time 58.5 years; drug costs Euro 60895 - 511718) seemed ineffective and expensive.

Commentary: Status of road safety in Asia.

OBJECTIVES: The objective of this article is to assess the status of road safety in Asia and present accident and injury prevention strategies based on global road safety improvement experiences and discuss the way forward by indicating opportunities and countermeasures that could be implemented to achieve a new level of safety in Asia. METHODS: This study provides a review and analyses of data in the literature, including from the World Health Organization (WHO) and World Bank, and a review of lessons learned from best practices in high-income countries. In addition, an estimation of costs due to road transport injuries in Asia and review of future trends in road transport is provided. RESULTS: Data on the global and Asian road safety problem and status of prevention strategies in Asia as well as recommendations for future actions are discussed. The total number of deaths due to road accidents in the 24 Asian countries, encompassing 56% of the total world population, is 750,000 per year (statistics 2010). The total number of injuries is more than 50 million, of which 12% are hospital admissions. The loss to the economy in the 24 Asian countries is estimated to around US$800 billion or 3.6% of the gross domestic product (GDP). CONCLUSIONS: This article clearly shows that road safety is causing large problems and high costs in Asia, with an enormous impact on the well-being of people, economy, and productivity. In many Asian low- and middle-income countries, the yearly number of fatalities and injuries is increasing. Vulnerable road users (pedestrians, cyclists, and motorcyclists combined) are particularly at risk. Road safety in Asia should be given rightful attention, including taking powerful, effective actions. This review stresses the need for reliable accident data, because there is considerable underreporting in the official statistics. Reliable accident data are imperative to determine evidence-based intervention strategies and monitor the success of these interventions and analyses. On the other hand, lack of good high-quality accident data should not be an excuse to postpone interventions. There are many opportunities for evidence-based transport safety improvements, including measures concerning the 5 key risk factors: speed, drunk driving, not wearing motorcycle helmets, not wearing seat belts, and not using child restraints in cars, as specified in the Decade of Action for Road Safety 2011-2020. In this commentary, a number of additional measures are proposed that are not covered in the Decade of Action Plan. These new measures include separate roads or lanes for pedestrians and cyclists; helmet wearing for e-bike riders; special attention to elderly persons in public transportation; introduction of emerging collision avoidance technologies, in particular automatic emergency braking (AEB) and alcohol locks; improved truck safety focusing on the other road user (including blind spot detection technology; underride protection at the front, rear, and side; and energy-absorbing fronts); and improvements in motorcycle safety concerning protective clothing, requirements for advanced braking systems, improved visibility of motorcycles by using daytime running lights, and better guardrails.

General practitioners' conceptions about treatment of depression and factors that may influence their practice in this area. A postal survey.

BACKGROUND: The way GPs work does not appear to be adapted to the needs of depressive patients. Therefore we wanted to examine Swedish GPs' conceptions of depressive disorders and their treatment and GPs' ideas of factors that may influence their manner of work with depressive patients. METHODS: A postal questionnaire to a stratified sample of 617 Swedish GPs. RESULTS: Most respondents assumed antidepressive drugs effective and did not assume that psychotherapy can replace drugs in depression treatment though many of them looked at psychotherapy as an essential complement. Nearly all respondents thought that clinical experiences had great importance in decision situations, but patients' own preferences and official clinical guidelines were also regarded as essential. As influences on their work, almost all surveyed GPs regarded experiences from general practice very important, and a majority also emphasised experiences from private life. Courses arranged by pharmaceutical companies were seen as essential sources of knowledge. A majority thought that psychiatrists did not provide sufficient help, while most respondents perceived they were well backed up by colleagues. CONCLUSION: GPs tend to emphasize experiences, both from clinical work and private life, and overlook influences of collegial dealings and ongoing CME as well as the effects of the pharmaceutical companies' marketing activities. Many GPs appear to need more evidence based knowledge about depressive disorders. Interventions to improve depression management have to be supporting and interactive, and should be combined with organisational reforms to improve co-operation with psychiatrists.

Benevolence and the value of road safety.

This study uses the contingent valuation method to elicit individuals' preferences for their own and others' safety in road-traffic. Whereas one group is asked about a private safety device for themselves, other groups are asked about safety devices for their children, household, relatives and the public. Support is found for the hypothesis that individuals are not purely selfish when it comes the safety of others.

Correlation of drug utilisation and morbidity at the municipality level. High use of antibiotics associated with low use of antihypertensives.

OBJECTIVE: The aim of the study was to explore the relationship between Swedish drug sales data per municipality and morbidity per municipality. The morbidity was expressed as "sickness numbers" which are assumed to function as proxy for morbidity. METHODS: Sickness numbers per municipality were correlated to volumes of drug sales per municipality in 2003. In addition, the sales volumes of antibiotics were correlated to the sales volumes of other drugs. RESULTS: We found significant positive correlations between municipality sickness numbers and sales volumes for most drug groups, except for antibiotics where the correlations were negative in all age groups. When the volumes of antibiotics were related to the volumes of other drug groups it was observed that municipalities with volumes of antibiotics above the national average had reduced volumes of cardiovascular drugs, especially of diuretics, beta blockers and calcium antagonists, all primarily used as antihypertensives. For ACE inhibitors and statins, no such relationship was found. CONCLUSION: The findings might suggest a link between infection and hypertension, but a cause-effect relation is not established.

General practitioners' conceptions of depressive disorders in relation to regional sales levels of antidepressive drugs. A study based on a postal survey and ecological data.

OBJECTIVES: To examine how local sales levels of antidepressive agents (ADs) correlated with GPs' conceptions of depressive disorders and of factors that may influence their work with depressed patients. DESIGN: A postal questionnaire survey to GPs requesting their conceptions of depression and their opinions of additional factors that may influence their work with depressed patients. GPs' conceptions and opinions were compared with local sales rates of ADs. SETTINGS: Three selected groups of Swedish municipalities: those with the highest, the average, and the lowest sales rates of ADs. SUBJECTS: All 535 GPs who worked in the selected municipalities. MAIN OUTCOME MEASURES: Spearman rank correlations for responses to the questionnaire with the sales levels of ADs. RESULTS: High sales levels correlated positively with a high evaluation of ADs' effectiveness in depression and panic disorders and were inversely correlated with the degree of appreciation of psychotherapy-based treatments. High sales levels were also associated with a high evaluation of GPs' own clinical and private experience, with a positive appreciation of the work with depressed patients and with a high level of participation in the pharmaceutical companies' activities. The demonstrated statistical correlations were not particularly strong and included less than half of the items. CONCLUSIONS: This ecological study confirms a number of statistical associations between sales levels of ADs and GPs' prevailing conceptions of factors related to depression. However, their explanatory value of the geographical sale variation appears limited. To further clarify this variation, studies employing information on individual GPs' conceptions and prescribing are required.

What shapes GPs' work with depressed patients? A qualitative interview study.

BACKGROUND: The ways that GPs treat depressed patients have been criticized in a number of studies. OBJECTIVE: To explore factors that shape how GPs work with depressed patients. METHODS: Seventeen GPs from the county of Orebro, Sweden participated in a qualitative semi-structured interview study. GPs' conceptions of factors shaping their way of working with depressed patients, especially continuing medical education (CME), commercial information, inter-collegial support, collaboration with psychiatrists and GPs' gender were recorded. RESULTS: Private life experiences as well as professional experiences from family medicine were more often stressed as formative factors than university education and training in psychiatry. Groups of GPs discussisng the doctor-patient relationship set out from real cases (Balint groups) and CME groups were regarded as good forms of education. Most GPs considered company-sponsored lectures valuable. Commercial drug information was seen as more powerful than non-commercial information and GPs wished for more non-commercial information. Collaboration with psychiatry consultants was perceived as insufficient, and GPs felt a need for more inter-collegial support. Traditional female qualities were generally seen as advantageous in the work with depressed patients. CONCLUSIONS: Many GPs consider personal qualities and experiences, including those of gender, to be more influential than academic education and professional literature. This reflects a preference for individual 'tacit knowledge'. Although tacit knowledge is indispensable in consultations, the low priority given to theoretical CME may make GPs less inclined to make optimal use of different therapeutic alternatives and also less critical of commercial marketing. CME on depression should start with GPs' individual tacit knowledge and assume a more independent stance from the drug industry.

Use of calcium channel blockers as antihypertensives in relation to mortality and cancer incidence: a population-based observational study.

PURPOSE: Treatment with blood pressure lowering drugs may reduce morbidity and mortality. However, the efficacy and effectiveness may differ between antihypertensive agents. The current investigation aimed to compare mortality and cancer incidence in hypertensive patients treated with calcium channel blockers (CCB) or with other antihypertensive drugs (AHD). METHODS: All patients in two outpatient clinics treated with AHD who underwent an annual check-up during 1989 or 1990 were selected. Fatal events were identified through 1997 and incident cancers through 1998. RESULTS: Two hundred and fourteen patients on CCB and 1029 on other AHD were identified. Overall mortality and the combined mortality from myocardial infarction and stroke were higher in CCB users; hazard ratios adjusted for sex, age, comorbidity and other and risk factors were 1.84 (95% CI 1.25-2.72) and 2.37 (95% CI 1.27-4.44), respectively. The risk estimates for cancer mortality and for cancer incidence did not differ significantly. CONCLUSIONS: Results from clinical trials as well as observational studies, including the present one, indicate a higher mortality risk and a higher cardiovascular morbidity risk associated with use of CCB. Accordingly, CCB should not be regarded as first line drugs in hypertension.