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The HTA is a multidisciplinary approach which is increasingly applied worldwide in order to support decision-makers in the introduction of health technologies. The application of HTA to vaccines is quite recent and linked to the increasing number of vaccines available or in development, especially to those intended to non pediatric immunization. In this article a description of the HTA approach used in the evaluation of the bivalent HPV vaccine in Italy is provided; moreover the reasons for keeping HTA process "alive" and identifying new or pending Public Health issues are discussed. In fact, the project raised questions and challenges about the standardization and sharing of HTA methods in Italy. Recently the need of updating the results is starting to be seen as urgent due to the evolution of scientific knowledge, the availability of the first results after technology introduction and the observed differences in vaccination strategies among Italian regions. Moreover in these last two years after the completion of the HTA project a number of new issues have risen in the Italian context as immunization rates, regional vaccination strategies, processes for vaccine selection and health economic issues.

Objectives: Over the last few decades, important changes occurred in the pharmacological approach to asthma control. However, the possible link between pharmacologic treatment and asthma death remains controversial., Study Design and Setting: Age-standardized asthma mortality rates were computed over the 1994-2004 period for France, Germany, Spain, the UK, and Italy. Rates for children and young adults 5 to 34 years of age, middle age adults 35 to 64 years of age, and elderly adults > or = 65 years. Joinpoint regression was performed to identify years where significant changes in mortality trends occurred. Consumption of inhaled long-acting beta-2-agonists (LABA), including inhaled corticosteroids (ICS) when combined with LABAs in a single inhaler, derived from sales estimates., Results: In 1994, the highest asthma mortality rates were in Germany (4.7/100,000), and the lowest ones were in Italy and Spain (0.5/100,000). Steady downward trends were observed in all the countries considered. The largest decline was registered in Germany and the smallest one was in the UK. LABA sales increased steadily since 1994, particularly in France, Spain, and the UK, reaching values around 14 Defined Daily Doses (DDD)/1,000 inhabitants in 2004., Conclusion: While the use of LABAs (with or without ICS) increased over the last decade, asthma mortality declined in major western European countries.

The importance of the patients point of view on their health status is widely recognised. Patient-reported outcomes is a broad term encompassing a large variety of different health data reported by patients, as symptoms, functional status, Quality of Life and Health-Related Quality of Life. Measurements of Health-Related Quality of Life have been developed during many years of researches, and a lot of validated questionnaires exist. However, few attempts have been made to standardise the evaluation of instruments characteristics, no recommendations are made about interpretation on Health-Related Quality of Life results, especially regarding the clinical significance of a change leading a therapeutic approach. Moreover, the true value of Health-Related Quality of Life evaluations in clinical trials has not yet been completely defined. An important step towards a more structured and frequent use of Patient-Reported Outcomes in drug development is represented by the FDA Guidance, issued on February 2006. In our paper we aim to report some considerations on this Guidance. Our comments focus especially on the characteristics of instruments to use, the Minimal Important Difference, and the methods to calculate it. Furthermore, we present the advantages and opportunities of using the Patient-Reported Outcomes in drug development, as seen by a pharmaceutical company. The Patient-Reported Outcomes can provide additional data to make a drug more competitive than others of the same pharmacological class, and a well demonstrated positive impact on the patient' health status and daily life might allow a higher price and/or the inclusion in a reimbursement list. Applying extensively the FDA Guidance in the next trials could lead to a wider culture of subjective measurement, and to a greater consideration for the patient's opinions on his/her care. Moreover, prescribing doctors and payers could benefit from subjective information to better define the value of drugs.

A combined DTPa-HBV-IPV/Hib vaccine containing diphtheria (D), tetanus (T), acellular pertussis (Pa), hepatitis B (HBV) and types 1, 2 and 3 inactivated polioviruses (IPV) extemporaneously mixed with a conjugated Haemophilus influenzae type b (Hib) vaccine (Group 1) was compared to the DTPa-HBV-IPV and Hib vaccines (Group 2) administered separately at 3, 5 and 11 months of age (n = 440). A microneutralization assay was used to detect antibodies against the 3 polio virus types (cut-off 1:8 dil), RIA for anti-HBs antibodies (cut-off 10 mIU/ml) and ELISA for antibodies against all other vaccine antigens (cut-off: 0.1 IU/ml for anti-tetanus and anti-diphtheria antibodies; 5 El.U/ml for antibodies against each of the 3 acellular pertussis antigens and 0.15 microg/ml for anti-PRP antibodies). Similar immune responses were observed in both groups 1 month after dose 2 as well as after dose 3. Six months after dose 2 however, the proportion of subjects maintaining an anti-tetanus antibody concentration > or = 0.1 IU/ml was lower in Group 2 and a slight group difference in favour of Group 1 was also observed for anti-PRP, anti-diphtheria and anti-polio type 1 antibody persistence prior to the third dose. The overall incidence of local and general solicited symptoms was similar in both groups. One subject discontinued study vaccination following an SAE considered to be related to vaccination. The DTPa-HBV-IPV/Hib combined vaccine is immunogenic and well tolerated when administered according to a 3, 5 and 11 month vaccination schedule and can therefore be considered as a feasible alternative to the separate administration of the pentavalent DTPa-HBV-IPV and the monovalent Hib vaccines.

Objective: Despite the fact that gastrointestinal disorders represent one of the most common reasons for medical consultations, formal assessment of patients' health-related quality of life (HRQOL) has been carried out only in a few studies, and in most cases generic questionnaires have been adopted. Because the specific issue of living with dyspeptic problems has been addressed in very few cases and no questionnaire has been shown to be appropriate for the Italian setting, a prospective project was launched to develop a specific HRQOL questionnaire for dyspepsia sufferers tailored to Italian patients but also appropriate in other cultural settings., Methods: The project consisted in a 3-yr, three-phase survey, in which different versions of the quality of life in peptic disease questionnaire (QPD) were developed through expert and patient focus groups and empiric field studies and then administered to patients recruited in five multicenter studies. Standard psychometric techniques were used to evaluate the validity, reliability, responsiveness, and patient acceptability of the QPD., Results: Three different versions of the QPD questionnaire were self-administered to more than 4000 patients. The final 30-item version, measuring three health concepts related to dyspeptic disease (anxiety induced by pain, social restriction, symptom perception), fulfilled the recommended psychometric criteria in terms of reliability and validity, correlated with health concepts measured with a well-known independent generic HRQOL instrument (the SF-36 Health Survey questionnaire) and was relatively invariant to diagnosis and sociodemographic variables; it also correlated with a measure of gastric pain frequency and was able to detect meaningful differences over time., Conclusions: Although further validation studies in different cultural and linguistic settings are mandatory before any firm conclusions can be drawn regarding the cross-cultural validity of the QPD, the data obtained provide evidence of the psychometric validity and robustness of the questionnaire when used in a fairly large, well-characterized population of Italian dyspeptic patients.

Drugs need to be evaluated both in terms of efficacy, safety and regarding the patient's perception of his own health status. For these reasons, sensible, reliable and patient-oriented instruments are needed, besides the methodologies for evaluation of drug efficacy and safety. Such instruments substantially evaluate Health related Quality of Life (HrQoL). Concerning gastric acid hypersecretion few papers are available, based on HrQoL questionnaires, both general and specific. A research project led us to develop through patients and physicians involvement, a specific instrument to evaluate HrQoL as to the various aspects of the peptic disease. The project started in 1993 through a series of 4 focus groups with gastroenterologists and patients, followed by the preparation of a questionnaire named QPD48. Such instrument was psychometrically validated through a study named Herqules 1, involving 176 gastroenterologists and 1774 patients. The psychometric analysis on QPD48 led to the re-issue of a questionnaire named QPD32 with Chronbach's alfa equal to 0.91, based on 3 factor-referenced subscales evaluating pain, induced anxiety, constrained daily living and awareness of symptoms and agents. Concerning the concurrent validity a one-way analysis of variance showed highly significant differences associated with attack frequency with substantial effect sizes ranging from 0.46 to 1.27 of a standard deviation in the full scale. QPD 32 is patent protected and will be used in clinical trials.

To determine whether it is possible to assess baroreceptor sensitivity by measuring changes in blood velocity in the carotid artery and changes in the heart rate, we performed a series of 108 experiments in 19 hypertensives aged 20-57 years (mean 46.6 +/- 8.6). In each experiment, we took simultaneous measurements of carotid artery blood flow velocity (Doppler technique), the brachial intra-arterial blood pressure and the heart rate, during a rapid and transient increase in blood pressure induced by injections of phenylephrine. We then calculated the maximum slope of the regression lines correlating blood velocity with the heart period (Trieste method) and blood pressure with the heart period (Oxford method). We obtained good accuracy from the Trieste method compared with the Oxford method, as assessed by the mean of the sum of the squares (difference + 5%, NS). After the administration of 4 mg oral lacidipine to 13 essential hypertensives, aged 37-54 years (47.6 +/- 5.3), baroreflex sensitivity was not changed, as assessed by either method (Oxford method 10.1 +/- 5.5 versus 9.8 +/- 6.2 ms/mmHg; Trieste method - 0.57 +/- 0.32 versus - 0.49 +/- 0.31 ms/Hz). The coefficients of variation for the two methods, calculated for the measurements taken before and after the administration of lacidipine, were not statistically different (Oxford method 25.0 +/- 18.4 versus 36.2 +/- 16.0; Trieste method 36.7 +/- 19.2 versus 39.7 +/- 19.2). The new non-invasive Trieste method thus showed the same accuracy and precision as the invasive Oxford method in measuring baroreflex sensitivity and can be used in pharmacological studies.

Most psychic disorders, such as anxiety, agitation and dementia are difficult to measure objectively since the scale of measure--psychometric tests--are often liable to subjective judgment--especially of clinicians or patients during self-rating scales. It become therefore necessary to use a complex way of measuring--a battery of tests--from which the results should be analyzed through multivariate statistic models. During this polycentric it was believed suitable to use the repeated multivariate analysis of variance, an instrument largely used in the data analysis of rating scale thanks to the flexibility of the generalized east squares methods. In this article the characteristics of this method and how to read its results will be discussed.