Harmonisation of ethics committees' practice in 10 European countries.

BACKGROUND: The Directive 2001/20/EC was an important first step towards consistency in the requirements and processes for clinical trials across Europe. However, by applying the same rules to all types of drug trials and transposing the Directive's principles into pre-existing national legislations, the Directive somewhat failed to meet its facilitation and harmonization targets. In the field of ethics, the Directive 2001/20/EC conditioned the way of understanding and transposing the "single opinion" process in each country. This led to a situation in which two models of research ethics committees organisation systems exist, being the model in which the "single opinion" is considered to be the decision made by a single ethics committee more effective and simpler in terms of administrative and logistic workload. METHOD: A survey was conducted in 10 European countries. Members of the European Clinical Research Infrastructures Network working party number 1, with expertise in the field of ethics, responded. RESULTS: There is a major heterogeneity in the composition of ethics committees among the surveyed countries based on the number of members, proportion of experts versus lay members and expertise of the scientific members. A harmonized education of the ethics committees' membership based in common curricula is recommended by the majority of countries. CONCLUSIONS: Despite the efforts for harmonization of the European Clinical Trial Directive, from an ethical point of view, there remains a plurality of ethics committees' systems in Europe. It is important to comprehend the individual national systems to understand the problems they are facing.

The cohabitation of academia and industry: What position do the medical journals take regarding opinion articles? / La cohabitación de la academia y la industria: ¿qué postura toman las revistas médicas en relación con los artículos de opinión?

Should medical journals publish editorials and educational articles written by authors who have financial conflicts of interest with pharmaceutical and biotechnology industries on whose products (or their competitors) they discuss? In the last 18 months, a controversy was sparked between The New England Journal of Medicine and BMJ, who took 2 opposite positions: the former stated that the negative bias against authors with conflicts of interest with industry is excessive and therefore accept articles from any expert, ensuring that they have the minimum possible bias. BMJ, in contrast, prohibits the publication of these types of article by authors who have financial conflicts of interest with industry. This article discusses the approaches of the 2 journals (and those of others) and reflects on this type of conflict in the medical profession.

Limitations of head-up tilt test for evaluating the efficacy of therapeutic interventions in patients with vasovagal syncope: results of a controlled study of etilefrine versus placebo.

OBJECTIVES: This study assessed the efficacy of oral etilefrine (10 mg three times a day) in preventing a positive response to head-up tilt testing. BACKGROUND: Previous reports have suggested that oral etilefrine can be effective either in preventing a positive response to head-up tilt testing or in reducing syncopal recurrences in patients with vasovagal syncope. Up to now most studies assessing drug therapy in these patients have been uncontrolled. METHODS: This was a randomized double-blind crossover study of etilefrine versus placebo in 30 consecutive patients with syncope and a baseline positive head-up tilt test. After the first test, patients had no treatment for 3 days and were randomized to receive etilefrine or placebo for 4 additional days. They underwent tilt testing under treatment and again after 3 days of washout; they then received the alternative treatment for 4 days, and a third test was performed. RESULTS: Head-up tilt test results were negative in 13 (43%) patients with etilefrine and 15 (50%) with placebo (p = NS). Therefore, the statistical power of the study was only 10%. The rate of positive responses decreased with repeated testing irrespective of the assigned treatment: A positive response was obtained during the second head-up tilt test in 20 patients (10 with placebo, 10 with etilefrine) but in only 12 during the third (7 with etilefrine, 5 with placebo) (p < 0.05). CONCLUSIONS: Oral etilefrine (10 mg three times a day) was not superior to placebo in preventing a positive response to head-up tilt testing. Despite a low statistical power, the high rate of negative response with placebo (50%) suggests that controlled trials are needed to assess the real efficacy of any treatment in patients with vasovagal syncope.

Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy.

OBJECTIVES: To assess the incidence and risk factors for hepatotoxicity associated with nevirapine. DESIGN: A prospective cohort study in a teaching and referral hospital involving all consecutive patients who were prescribed a nevirapine-containing antiretroviral regimen between September 1997 and May 2000. METHOD: Cutaneous and hepatic adverse reactions and clinical hepatitis were assessed. Blood analysis including plasma HIV-1 RNA CD4 cell counts, liver chemistry tests, and serology for hepatitis B and C viruses. Hepatotoxicity was defined as an increase of at least threefold in serum alanine aminotransferase or aspartate aminotransferase levels compared with baseline values. RESULTS: Of a total of 610 patients, 82 (13.4%) were antiretroviral naive when commencing nevirapine, and 46.2 and 8.9% were coinfected with hepatitis C and B viruses, respectively. Median duration of exposure to nevirapine was 8.7 months (interquartile range 3.4--14.3). Hepatotoxicity developed in 76 (12.5%), an incidence of 13.1/100 person-years. Kaplan--Meier estimated incidence of hepatotoxicity at 3, 6 and 12 months was 3.7, 9.7 and 20.1%, respectively. In seven (1.1%) patients, hepatotoxicity was associated with clinical hepatitis, which was reversible upon discontinuation of therapy. Multivariate analysis identified the duration of prior exposure to antiretroviral drugs, hepatitis C virus, and higher baseline levels of alanine aminotransferase as independent risk factors for hepatotoxicity. CONCLUSIONS: Hepatotoxicity but not clinical hepatitis was common in HIV-1-infected patients receiving nevirapine-containing regimens and the incidence steadily increased over time. Prolonged exposure to any antiretroviral therapy, coinfection with hepatitis C virus and abnormal baseline levels of alanine aminotransferase identified patients at a higher risk.

Perioperative antibiotic prophylaxis in Spanish hospitals: results of a questionnaire survey. Hospital Pharmacy Antimicrobial Prophylaxis Study Group.

A questionnaire survey was sent to a random sample of the Spanish network of National Health System public acute-care hospitals. Of responding institutions (representing 25% of Spanish hospital beds), nearly 75% had active surveillance programs for the prevention and control of surgical-site infections (SSIs), but only 20% performed postdischarge surveillance. Overall, perioperative antibiotic prophylaxis (PAP) was used in 84% of all surgical procedures. For 77% of procedures, there were written guidelines for the choice and use of PAP. Cefazolin was the most commonly used antibiotic (38%). Duration of PAP was shorter than 24 hours in 75% of procedures, and only a single dose was given in 52% of procedures. PAP was commonly used in breast (52%) and inguinal hernia repair (69%) procedures, as well as in laparoscopic abdominal surgery (86%). In summary, the use of PAP in Spanish hospitals is adequate, but improvements can be made in the frequency of prolonged PAP and in the use of broad-spectrum antibiotics. Surveillance systems for SSI, including postdischarge follow-up, also should be improved.

Adverse drug reactions leading to hospital admission.

This article describes the implementation of a simple method of drug surveillance set up at a hospital emergency ward. From a total of 48,678 patients admitted, the medical records of those presenting with one or more of a pre-established list of admission diagnoses (n = 7728; 15.8%) were checked. Of these 554 (1.1%) were diagnosed as experiencing an adverse drug reaction. When the medical record suggested an adverse drug reaction, drugs taken before admission were ascertained by interviewing the patients with a structured questionnaire. After excluding upper gastrointestinal bleeding (226 cases) and certain bone marrow blood dyscrasias (42 cases), 286 patients with drug-induced events leading to hospital admission were identified in 2 years. Fatal adverse drug reactions, previously undescribed reactions, and some specific examples, such as digoxin-amiodarone interaction, drug-induced pancreatitis, nicardipine-induced AV block, severe skin reactions, and NSAID-induced bronchospasm, are described. Basically, this method consists of assembling series of cases systematically, and is therefore devoid of selective bias. In addition, it allows a more in-depth clinical and anamnesic study of specific diseases, as compared with voluntary reporting.

[Comparative analysis of articles published by Spanish authors (1993-1997) in biomedical journals with high impact factor]. / Análisis comparativo de las publicaciones realizadas por autores españoles (1993-1997) en revistas clínicas con factor de impacto elevado.

BACKGROUND: To identify the Spanish scientific production amongst different areas of clinical knowledge, and to compare it with those of five other European Union countries. METHOD: Review of MEDLINE data base, for the period 1993-1997. Search limited to four journals, selected, for 10 different medical specialties (Cardiology, Endocrinology, Infectious Diseases, Gastroenterology-Hepatology, Haematology, Nephrology, Pneumology, Neurology, Oncology, Rheumatology). Articles published by authors from Germany, France, Italy, The Netherlands, Sweden and Spain. Journals included in the Internal Medicine subject classification were independently analysed. Data were also related with several econometric indexes. RESULTS: A total of 1,763 original articles published by Spanish authors were identified in the journal's sample over the analysed period (2.08 articles per 100 all published articles). Spain contributes to the total achieved by the six European countries analysed with 9.07 articles per 100 published articles. Gastroenterology-Hepatology was the medical specially which has more articles published by Spanish authors (total: 338 articles; 4.15 articles/100 published articles); and Oncology the one with less articles published (1.26 articles/100 published articles). The mean IF value per journal by article is highest for Gastroenterology-Hepatology (4.86 FI/article) and lowest for Pneumology (2.42 FI/article). Spain is the last amongst all six European countries analyzed in Endocrinology, Oncology and Haematology, and second to last in all others except for Gastroenterology-Hepatology (4th place). Mean cost for each article produced by Spanish authors in the analyzed sample was 0.49 US $ according the health expenditures per capita, and 0.07 US $ according the R+D expenditures per capita. Data from the independent analysis of Internal Medicine journals also showed that Gastroenterology and Hepatology is the subspecialty with a higher number of papers published in those journals. CONCLUSIONS: All efforts devoted to improve the quality of Spanish biomedical research, specially in clinical research, had produced positive, but uneven, results, measured by the number and impact factor of original articles published in top ranked biomedical journals. The overall distribution of high impact factor scientific production by specialties is poor when compared to the European Union countries included in the analysis. Those results showed several improvement opportunities. Besides increasing the overall budget for R+D, its is likely that the time has come for backing the highest quality Spanish biomedical research, the one that offers greater and better chances for achieving scientifically valid results, and is published in high impact factor biomedical journals.

[Vancomycin and teicoplanin use as antibiotic prophylaxis in cardiac surgery: pharmacoeconomic study]. / Vancomicina y teicoplanina como profilaxis antibiótica en cirugía cardíaca: estudio farmacoeconómico.

BACKGROUND: To assess the economical impact of vancomycin use versus teicoplanin use as antibiotic prophylaxis for patients undergoing cardiac surgery for valve replacement (VR) and coronary artery by-pass (CABS) procedures. PATIENTS AND METHODS: This is an ancillary cost minimization analysis of a double blinded, parallel groups, randomised clinical trial (RCT), with the main objective of comparing the safety and efficacy of these antibiotics. 500 patients were included in the study; 267 in the CABS group and 233 in the VR group. The CABS patients received 1 g vancomicin or 400 mg teicoplanin, plus 150 mg netilmicin. The VR group received a second dose of each drug after extracorporeal circulation. In order to calculate the costs we considered the direct cost of the drug, the i.v. mix and the administration costs, together with personnel and structure costs. We considered two different situations: the administration of drugs within the surgical room theatre and in the medical ward. RESULTS: The demographic data of both groups were comparable. The frequency of severe adverse drug reactions (ADR) were similar (0.4%) in both groups, as well as the post-operative infection rates (8.6%). Differences were seen in the frequencies of low severity ADRs: 20.4% in the vancomycin group and 1.6% in the teicoplanin group. When the antibiotics were administered in the surgical room, among CABS patients the costs were 8,265 pts. for the teicoplanin group and 12,005 pts. for the vancomycin group; while among VR patients, costs were respectively 11,661 pts. and 14,528 pts. Administration costs of teicoplanin and vancomycin within a medical ward setting, however, the costs were 6,740 pts. and 2,809 pts. for CABS patients, and 5,308 pts. and 10,140 pts. for VR patients, respectively. CONCLUSIONS: The costs of antibiotic prophylaxis among cardiac surgery patients heavily depends on the setting and circumstances of drug administration. The minimization cost analysis indicates that teicoplanin is the most cost-effective option if the drug is administered within the surgical area, while vancomycin is the less costly option when administered within the medical ward. However, if the second option is to be chosen, it is necessary to assure the right plasmatic drug levels of the antibiotic at the beginning of the surgical procedure.

[Omeprazole: a new treatment for paranasal sinus polyps in Widal syndrome. Preliminary study]. / Omeprazol: un nuevo tratamiento de la poliposis nasosinusal en el síndrome de Widal. Estudio preliminar.

A preliminary report is made of the potential therapeutic effect of omeprazol in reducing nasosinusal polyps. This study is based on the empirical observation of nasal airflow improvement in patients suffering from nasosinusal polyposis after administering omeprazol. Different phases of the study suggested that patients with Widal's syndrome benefited the most. Based on the results of this study, we have undertaken a randomized, parallel, double-blind, placebo-controlled clinical trial.

Clinical trials with drugs? Based on 2 projects in Alzheimer's disease and malaria.

The biomedical research act (BRA) regulates clinical research in humans, but not that related to clinical trials with medicinal products. This article describes the scientific and regulatory foundations supporting 2 projects which could be observed as clinical trials, can follow the BRA requirements. One is a positron emission tomography study with radiopharmaceutical to determine the presence of amyloid-ß protein deposition in certain areas of the brain of cognitively healthy adults. The other is a study on controlled malaria infection in healthy volunteers using the inoculation of aseptic, purified and cryopreserved Plasmodium falciparum sporozoites. Since in both studies subjects undergo invasive procedures, the BRA requires the approval of the study by the relevant regional health authorities. These 2 studies have been the first ones that have used this regulatory procedure in Catalonia.