Usability of daily SF36 questionnaires to capture the QALD variation experienced after vaccination with AS03A-adjuvanted monovalent influenza A (H5N1) vaccine in a safety and tolerability study.

BACKGROUND: This study aims to describe the short-term reactogenicity of the AS03-adjuvanted H5N1 vaccine expressed through adverse events (AEs) and quality-adjusted life-day (QALD) scores. The AEs are likely to be short-term and therefore the quality of life (QoL) questionnaire, SF-36v2, was administered daily to record changes over seven days. A more sensitive application of this instrument should allow for a better understanding of short-term tolerability of adjuvanted vaccines. METHODS: Participants (N = 50) received a 2-dose vaccination schedule. Solicited (collected daily: days 0 to 7 [post dose 1] and 21 to 28 [post dose 2]) and unsolicited (collected weekly until day 21) AEs were collected via diary cards. The QoL questionnaires were completed daily (days 0-6) and weekly (days 0, 6, 21, 27) after dose one. Questionnaire data were transformed into SF-6D scores to report QALDs. It was hypothesized post-hoc that the QALD and daily AEs scores should correlate if discrete QoL-changes were captured. RESULTS: Pain (92%) and muscle ache (66%) were the most commonly reported solicited local and general AEs respectively, neither increased in intensity nor in frequency after dose 2. No safety concerns were identified during the study. A correlation between the daily AEs and QALD scores existed (correlation coefficient, - 0.97 (p < 0.001)). The impact of the AEs scores on the QALD was marginal (- 0.02 max for one day). CONCLUSION: Similarly with other H5N1 studies, no safety concern was identified throughout the study. Some time-limited variations in QALD-scores were reported. Our results imply that daily administration of the SF-36v2 captures changes in QALD-scores. TRIAL REGISTRATION: ClinicalTrials.gov . NCT01788228. Registered 11 February 2013.

Measuring the cost of a pediatric vaccine administration in the UK.

The administration of a vaccine dose involves a series of activities prior to and on the day of vaccine delivery. Total vaccination cost should include the cost of each activity, which is often not done or poorly reported. To calculate those costs a field study was performed in 6 United Kingdom (UK) sites (General Practitioner (GP) practices) during a 4-month period (April-June 2015). First, a workflow map of all the relevant vaccine-related activities per site was obtained through interviews. Second, time estimates for activities happening prior to the vaccination day were obtained through interviews and associated costs were calculated. A prospective, non-interventional study using Time & Motion (T&M) methodology was used to measure time for activities happening on the day of vaccination. Consumables, wastage, and guardian time were also collected. Third, the time for each task and for all tasks combined during the T&M study was analyzed using a random intercept model to account for site effect. Hundred and twenty-three T&M observations with approximately 20 per site were collected and were equally stratified by vaccination visit during the first year of a baby's life. Total cost per visit was £11.9 (site range: £8.6-£17.0) when supply cost and time for activities prior to the vaccination day were included. Time per dose administrated was 7.1 min (site range: 5.7-9.2) and the associated cost was £4.3 (site range: £3.1-£6.2). The study demonstrates an accurate reflection of the time and cost involved in a vaccine dose administration in a pediatric setting in the UK. The amount measured is consistent with the current National Health Services fee schedule.

Improvement in hospital Quality of Care (QoC) after the introduction of rotavirus vaccination: An evaluation study in Belgium.

During each winter period hospital emergency rooms and pediatric wards are often overwhelmed by high patient influx with infectious diseases leading to chaotic conditions with poor quality of care (QoC) delivery as a consequence. The conditions could be improved if we were able to better control the influx by introducing for instance better prevention strategies against some of the most frequent infectious diseases. New prevention strategies using vaccination against rotavirus infection were introduced in Belgium in November 2006. We developed a measure of hospital QoC suitable for assessing the impact of pediatric rotavirus vaccination. The study is retrospective collecting routine data on bed and staff management in one pediatric hospital in Belgium. The data were divided in pre- and post-vaccination periods during rotavirus-epidemic and non-epidemic periods. The scores were constructed using Explanatory Factor Analysis (EFA). All patients enrolled were admitted to the pediatric ward over the period from 1 January 2004 to 31 December 2009. The results of the epidemic period indicated that bed-day occupancy, bed-day turnover and unplanned readmissions for acute gastroenteritis were lower in the post-vaccination compared with the pre-vaccination periods. The QoC scores were therefore significantly lower (indicating improved QoC) after the introduction of rotavirus vaccination, compared with pre-vaccination. The data suggests that the reduction in the winter peak of rotavirus-related hospitalizations after the introduction of the vaccine reduces pressure on hospital resources and improves the quality of hospital care. The findings should be further tested in similar settings.

Cost-effectiveness of infant vaccination with RIX4414 (Rotarix) in the UK.

This study estimated the cost-effectiveness of infant rotavirus vaccination with Rotarix in the UK, taking into account community rotavirus infections that do not present to the healthcare system. A Markov model compared the costs and outcomes of vaccination versus no vaccination in a hypothetical birth cohort of children followed over a lifetime, from a societal perspective and the perspective of the National Health Service (NHS). The model estimated costs and quality-adjusted life-years (QALYs) lost due to death, hospitalisation, general practitioner (GP) consultation, emergency attendance and calls to NHS Direct for rotavirus infection in children aged <5 years. Time lost from work and parents' travel costs were also included in the societal perspective. The base case cost-effectiveness ratio for vaccination compared with no vaccination was pound23,298/QALY from the NHS perspective and pound11,459 from the societal perspective. In sensitivity analysis, the most important parameters were hospitalisation cost and number of GP consultations. Addition of Rotarix to the paediatric vaccination schedule would be a cost-effective policy option in the UK at the threshold range ( pound20,000-30,000/QALY) currently adopted by the National Institute for Health and Clinical Excellence.

Resource use and cost analysis of managing abnormal Pap smears: a retrospective study in five countries.

OBJECTIVE: To evaluate and compare treatment patterns and related resource use and costs in women with abnormal cervical smears in five countries. METHODS: Data from patient charts were collected for a minimum of 24 months, starting from the first recorded abnormal cervical smear. Costs, from the public health perspective, were calculated based on country-specific unit costs per procedure and expressed in euros. RESULTS: A total of 3,380 patient charts were reviewed. Subjects with suspected or detectable cervical cancer were excluded from the analysis (n = 380). A significant age difference of 1.8-2.6 years was observed between the lowest and highest severity of cytological and histological types (p < 0.05). The correlation between cytology and histology results was weak overall (35.8%) and varied widely between countries (ranging from 48% for Australia to 29.7% for the UK). As expected, countries with an organised screening programme (UK, Australia) diagnosed and initiated treatment at earlier disease stages. These countries demonstrated a much lower and narrower cost band for more advanced histological types. In contrast, other countries (Germany, Italy, Spain) followed an opportunistic screening programme in which advanced disease was diagnosed and treated at much higher and more varied costs. Histological, not cytological, results were the main factor underlying the cost differences per type. CONCLUSION: Costs and treatment patterns in women with abnormal cervical smears differ among countries due to the type of screening programme (organised versus opportunistic) and, consequently, the histological type. These results need to be taken into consideration when designing cost-effectiveness studies which include cervical cancer screening data.

Management of women with abnormal cervical cytology: treatment patterns and associated costs in England and Wales.

OBJECTIVE: To evaluate the time from abnormal Papanicolaou smear detected during routine screening to the initiation of investigation and treatment of subjects and to evaluate its related costs. DESIGN: Retrospective study of clinical records from women with abnormal cervical smears. SETTING: Six specialist gynaecology/colposcopy clinics in England and Wales. SAMPLE: Six hundred subsequent women (100 per clinic) with first abnormal cervical smear result at the specialist gynaecology/colposcopy clinic. METHODS: Details of all clinic visits, tests and procedures during 24 months starting from the first abnormal cervical smear were collected from the year 2002. MAIN OUTCOME MEASURES: Patterns of management after initial abnormal smear, time to start the investigation and/or treatment expressed in days/months and treatment costs by cytology and histology grades. RESULTS: Significant age differences were observed between women with early grades of precancer lesions (32 years) and cancer (49 years) (P < 0.05). Subgroup analysis of women younger than 26 years indicates a representation of this age group in all the histology grades including cancer. Median time to initiate the investigation and/or treatment was 50 days. In contrast, for 5% of women, delay in management lasted for >1 year. Colposcopy and repeated cervical smears were the most frequent systematic investigations performed, while the large loop excision of the transformation zone procedure was the principal therapeutic procedure. Analysis of average treatment costs by referral cytology showed small differences between the three grades of cytological diagnoses (mild dyskaryosis, 408.96 British pound; moderate dyskaryosis, 442.55 British pound and severe dyskaryosis, 493.74 British pound). Analysis by histology grade showed that the cost for women with a negative result (263.34 British pound) differed markedly from that for women with cervical intraepithelial neoplasia (CIN) (CIN1, 419.39 British pound; CIN2, 572.29 British pound; and CIN3, 584.92 British pound). CONCLUSION: Time to investigation could be improved for a subgroup of women. Costs associated with investigation and treatment of women with abnormal cervical smears differ significantly between analyses by cytology and histology grade. This needs to be borne in mind when designing cost-effectiveness studies of cervical screening.

Estimating resource use and cost of prophylactic management of neutropenia with filgrastim.

The study objective is to develop a methodology for the measurement of time, resource use and cost of the prophylactic management of neutropenia with filgrastim in different settings where the drug is routinely used: in-hospital care, outpatient care and home care. The activity-based costing method is used to analyse the cost of managing prophylactically neutropenia and comprises four steps. First, department heads in each of the chosen settings were selected and interviewed to obtain key elements in the workflow that involves the management of neutropenia, followed by the second step involving in-depth, structured interviews of key personnel. The third step was the measurement of the time required for frequently occurring activities in monitoring neutropenia and the administration of filgrastim by a study nurse. Finally, information on resource unit costs and personnel salaries were collected from the administration units to calculate an average cost. Sensitivity analyses were undertaken on estimated variables in the study. A list of eight to 14 consecutive activities linked to the prophylactic management of neutropenia was observed. The number and type of activities do not differ between an in-hospital oncology ward and an outpatient setting except for blood samplings. The difference is more pronounced between hospital and home care settings, as in the latter the patient performs many of the activities him/herself. The cost estimate per setting for prophylactic drug use is 6.30 Euros for in-hospital care, 3.67 Euros for outpatient care and 5.49 Euros for home care. Taking the two most frequently occurring scenarios per chemotherapy cycle (i.e. with or without febrile neutropenia), the following cost estimates are obtained: 60.41 Euros for a patient with febrile neutropenia and 56.77 Euros for a patient without febrile neutropenia, excluding drug costs. With the activity-based costing method it is possible to accurately demonstrate cost savings in the management of neutropenia using the newer drug therapies.

[Necessary harmonization of health cost assessment. Autologous peripheral blood progenitor cell transplantation in France]. / Vers une nécessaire harmonisation des évaluations de coûts en santé

BACKGROUND: The purpose of this study was to determine to what extent methods used to assess health cost affect the total cost of a therapeutic procedure. METHOD: We assessed total cost of 160 consecutive therapeutic intensification procedures using autologous blood progenitor cell transplantation, 95 for lymphoma and 65 for breast tumor. RESULTS: The average total cost of the therapeutic intensification for patients with lymphoma was 227156 francs (34630 euros), including 60720 francs (9257 euros) for mobilization, 14947 francs (22402 euros) for the treatment period and 19489 francs (2971 euros) for secondary hospitalization. The average total cost for patients with a breast tumor was 199626 francs (30433 euros), including 39269 francs (5987 euros) for mobilization, 14912 francs (22737 euros) for the treatment period, and 11215 francs (1709 euros) for secondary hospitalization. CONCLUSION: We compared our findings with those from six earlier French studies. Differences in the methodologies used focuses attention on the need for incentives for better harmonization of health cost assessment.

Summary measures and statistics in the analysis of quality of life data: an example from an EORTC-NCIC-SAKK locally advanced breast cancer study.

Quality of Life (QL) is now included as an endpoint in many phase III cancer clinical trials. Numerous statistical techniques have been presented in the literature to analyse QL data but there is still no agreement as to what is the optimal approach of analysis. In this paper we, therefore, present and compare various techniques which have all appeared in the literature and which may be globally described as summary measures and summary statistics. These techniques are illustrated using data from an EORTC clinical trial in locally advanced breast cancer (EORTC trial 10921). It is also explained in this paper how and when these techniques may be used in other cancer settings. For EORTC trial 10921, it is shown that by choosing different techniques different conclusions may be drawn concerning the QL outcome. This highlights the importance of choosing an appropriate primary statistical method and for describing it a priori in the protocol and analysis plan. In this paper, we show the importance of performing sensitivity or supportive analysis to support conclusions drawn from the primary analysis.

Comparison between cefprozil and penicillin to eradicate pharyngeal colonization of group A beta-hemolytic streptococci.

BACKGROUND: Our objective was to perform a prospective, randomized, double blinded study of cefprozil and penicillin therapy to eradicate group A beta-hemolytic streptococci (GABHS) in children who were bacteriologic failures after receiving a standard 10-day course of penicillin treatment for GABHS pharyngitis. METHODS: Children and adolescents 2 to 18 years of age were eligible for the study. From 3 to 7 days after completing oral penicillin therapy for pharyngitis caused by GABHS, the study was explained, informed consent was obtained, a history and physical examination were completed and a throat culture was performed. Children with throat cultures positive for GABHS were randomized to receive either cefprozil or penicillin for 10 days. Children who were bacteriologic failures after administration of the first study drug were crossed over to receive the alternate drug. RESULTS: Of 180 enrolled children 66 (37%) had throat cultures positive for GABHS. Seventeen were excluded from the study, leaving 49 who completed the protocol. Of the 49 participants 26 received cefprozil initially whereas 23 received penicillin. GABHS were eradicated from the pharynx of 73% of children who received cefprozil as the first antibiotic compared with 39% of penicillin recipients (chi square, 5.748, 0.01 < P < 0.025). After crossover of failures, the final efficacy rate for cefprozil was 65% compared with 36.7% for penicillin (chi square, 5.523, 0.01 < P < 0.025). CONCLUSIONS: Cefprozil was more effective than penicillin in treating children who were bacteriologic failures after a standard 10-day course of oral penicillin.

The European Randomized Study of Screening for Prostate Cancer: an update.

BACKGROUND: A consensus meeting on screening and global strategy for prostate carcinoma, held in Antwerp in 1994, determined the willingness among European cancer prevention centers to pursue vigorously the collaborative formation of a multinational randomized screening trial. This trial was to be named the European Randomized Study of Screening for Prostate Cancer (ERSPC). METHODS: During the years prior to that meeting, several feasibility trials were conducted in Antwerp and Rotterdam to evaluate the pitfalls and problems of a randomized procedure for population screening. Today, five centers in five European countries share their study work and results via the ERSPC, and others are lining up to join this massive effort. Regular meetings and specific work groups enable the research centers to compare their data, because the trial methodology differs slightly from one center to another. RESULTS: However, a common work strategy and analysis of the data has recently been reached, and the first study results of the trial (evaluating 180,000 men over a 10-year screening period) are expected by the year 2007. CONCLUSIONS: A randomized trial of prostate carcinoma screening is set up in Europe currently with five participating centers from five countries. First overall effect results of regular screening are expected after a 10-year period of follow-up.

Prostate volume and cancer in screening programs.

BACKGROUND: Prostate cancer screening is studied in a randomized trial in Antwerp, Belgium. The case group receives three screening tests (DRE, TRUS, and PSA). Intermediate evaluation shows that only 1/3 of the biopsy results is positive (35/125). The proposed analysis identifies variables that determine the biopsy outcome. METHODS: Multiple logistic regression analysis is used to regress biopsy results (n = 125) by age (60-74), PSA, PSA-D, prostate volume, TRUS, and DRE. Continuous variables are transformed into quartile values. Robustness of the outcome is tested with ROC and sensitivity analysis on age. RESULTS: Biopsy outcomes are best explained (82.3%) by PSA, DRE, and DRE related to volume. Volume is more sensitive than age to explain the biopsy result. PSA-D, instead of PSA, does not procure more precise information when a high PSA cut-off level is used. Restricting the analysis to the 60-70-year-old age group shows that volume is more sensitive. ROC-analysis confirms the findings. CONCLUSIONS: When performing prostate cancer multitest screening among a wide age range, the use of uniform screening criteria is difficult to accept due to differences in prostate volume. Logistic regression analysis is an appropriate method to identify cut-off levels for prostate volume.

Overall and meal-specific macronutrient intake in Belgian primary school children.

In the fall of 1991, dietary intake of 1,321 primary school children aged 6-12 years was studied in 79 schools in an area called 'South Campine' in Flanders-the Dutch-speaking part of Belgium. Assessment of dietary intake was done using the '24-hour estimated food record method'. The energy distribution over the macronutrients showed no significant difference between boys and girls. On average 37.2% (SD 7.88%) of energy came from total fat and 15.4% (SD 3.70%) from saturated fatty acids; 49.0% (SD 7.87%) from total carbohydrates with 21.8% (SD 5.84%) from complex carbohydrates and 27.7% (SD 7.79%) from free sugars. Snacks accounted for on average 19.5% (SD 10.83%) of total energy intake; on average 55.7% (SD 21.22%) of the energy in these snacks was represented by free sugars. Lunch and dinner had very high fat contents (around 40% of energy). Already at this young age, the dietary pattern is deviating strongly from the recommended population nutrient goals.

Total healthcare budget: assigning priority and level of asset allocation to the diagnosis and management of urologic diseases.

During the past decade increasing concern has developed as to how money should best be allocated in the healthcare sector and to the different disciplines within health care. In the Western world, healthcare budgets increase dramatically each year, even during periods of economic recession. There are many reasons explaining this evolution, but publicly funded healthcare systems, as in the United Kingdom, appear to control their growth more effectively than the private systems as, for instance, in the United States. The bulk of the increase in healthcare expenditure happens to be attributed to elderly people who are becoming high consumers of healthcare facilities. There are, however, two important ways to tackle the problem: one is based on free market regulation systems, introducing diagnosis related groups and resource based relative value scales, as in the United States. The other starts from evaluating the needs and the demands of the population and, based on these results, tries to build up an appropriate healthcare system, as in The Netherlands. In the realm of urology where most of the workload is concentrated around older patients, one can foresee difficulties concerning budget allocation. New medical treatments are introduced, demanding new management skills of the urologist. This should involve new ways of evaluating the benefits of the interventions. Quality of life measurements seem to be crucial for the future where, for cost-effectiveness reasons, more care than cure could be the new function of the urologist.