Problemas bioéticos en la investigación de nuevas vacunas: ¿obedecen a razones de salud pública? / Bioethical problems in researching new vaccines: Do they respond to public health reasons?

Los problemas éticos de las investigaciones sobre vacunas han crecido en las últimas décadas en frecuencia y magnitud debido a la posición dominante de la industria farmacéutica en el desarrollo de esos estudios. Las tradicionales cuestiones de seguridad y eficacia se han visto agravadas por el conflicto de intereses introducido por la competencia comercial en un mercado a escala global de miles de millones de dólares. La integridad profesional de los investigadores, la responsabilidad moral de los patrocinadores, y la regulación y control por parte de los Estados nacionales, se muestra cuestionada en varios ejemplos. Los resultados de estos cambios son las amenazas a la protección de los derechos de las personas incluidas en estas investigaciones y el discutible progreso que resulta para la salud pública.

The ethical problems in vaccine research have grown in frequency and magnitude in last decades, due to the dominant place of the pharmaceutical industry in the development of such studies. Traditional issues of security and efficacy have been aggravated by the conflicts of interests introduced by commercial competition in a global market worth billions of dollars. We present here a few examples in which the professional integrity of researchers, the moral responsibility of sponsors, and the public regulation and control by national States are put into question. The consequences of these changes represent serious threats to the rights of people included in these studies as well as disputable progress for public health.

Cinitapride Extended-Release Tablets Versus Cinitapride Immediate-Release Tablets in the Treatment of Functional Dyspepsia and Gastroesophageal Reflux Disease : A Randomized Clinical Trial.

Prokinetics are commonly used for Functional Dyspepsia (FD) and GastroEsophageal Reflux Disease (GERD). Aims and Objectives: To evaluate the safety and efficacy of cinitapride Extended-Release (ER) tablets versus conventional cinitapride Immediate-Release (IR) tablets for the treatment of FD and GERD. Materials and Methods: Patients with FD and GERD received either cinitapride ER 3 mg tablets OD or cinitapride IR 1 mg tablets TID for 4 weeks in this randomized, multicentre study. Change in the mean intensity score of gastrointestinal (GI) symptoms (overall and individual) at the end of the study and at each weekly follow up visit as compared to baseline, patients with complete resolution of GI symptoms, patients with > 50% reduction from baseline in overall intensity score, rescue medication use and overall efficacy were recorded. The safety variables were reported adverse events (AEs), laboratory parameters, electrocardiogram, and overall tolerability. Unpaired t test, chi square test or Fisher’s exact test were used for analysis. p < 0.05 was considered significant. Results: Total 218 patients were enrolled Cinitapride ER tablets were non-inferior (non-inferiority margin -2.5) to cinitapride IR tablets for the change in the mean overall GI symptom intensity score at the end of the study as compared to the baseline (treatment difference - 0.2 (95% CI: -2.2, 1.7)); also, no significant difference was found for other efficacy variables (p > 0.05). Eight AEs of mild-to-moderate intensity were reported. There was also no difference in the overall tolerability between the study groups (p = 0.875). Conclusions : Both the study treatments were comparable in terms of safety and efficacy for the treatment of FD and GERD.

Randomised, double-blind, comparative study to evaluate the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia.

Prokinetic agents like itopride hydrochloride and mosapride citrate are commonly used in the management of functional dyspepsia. However, in a recently conducted international, multicentric study, efficacy of 3 different regimens of mosapride was shown to be comparable to placebo. The objective of this phase 4 randomised, double blind, prospective study was to compare the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia among patients attending the gastroenterology outpatient department of a tertiary care hospital. Ganaton 50 mg or mosapride citrate 5 mg three times daily before meals for a period of 2 weeks was administered orally. Thirty functional dyspepsia patients in each group (total = 60) were randomised to receive itopride hydrochloride or mosapride citrate treatment for 2 weeks. In itopride versus mosapride groups, global efficacy as judged by patients was excellent in 17 versus 9 (p < 0.05) and poor in 0 versus 3 (p < 0.05). In itopride versus mosapride group global efficacy as judged by physician was excellent in 24 (80%) versus 15 (50%) and poor in 0 (0%) versus 3 (10%) patients respectively. The global efficacy was rated as excellent to good in significantly (p < 0.05) more number of patients in itopride (93.3%) group as compared to mosapride (63.33 %) group. None of the patients reported any adverse events with itopride treatment. In the mosapride group 5 patients (16.7%) reported adverse events. Two patients (6.7%) were withdrawn from mosapride treatment due to adverse events. The physician rated global tolerability ofitopride versus mosapride treatment as excellent in 23 (76.7%) versus 8 (26.7%) (p < 0.05) and poor in 0 (0%) versus 6 (20%) patients respectively. It may be concluded that ganaton (itopride hydrochloride) is superior in efficacy and safety over mosapride citrate in the management of functional dyspepsia.

Comparative evaluation of the efficacy and tolerability of itopride hydrochloride and domperidone in patients with non-ulcer dyspepsia.

BACKGROUND: Prokinetic drugs are widely used for treatment of non-ulcer dyspepsia (NUD). AIMS AND OBJECTIVES: To assess the efficacy and tolerability of a new prokinetic agent, itopride hydrochloride in patients of NUD and compare it with domperidone. METHODS: Fifty-six patients who fulfilled the inclusion and exclusion criteria were enrolled in the study. Patients underwent upper gastrointestinal endoscopy to rule out organic pathology as a cause for their symptoms. The patient's symptoms were graded on a 4-point scale (0 to 3) at the beginning of treatment and at the end of Week-one and Week-two Patients were randomly allocated to receive either one tablet of itopride hydrochloride 50mg three times daily or one tablet of domperidone 10mg three times daily for two weeks. Pre-treatment and post-treatment hemogram, liver function and renal function tests, prolactin level and ECG were done in all patients. The response to therapy was evaluated by assessing the relief of symptoms at the end of two weeks on a 5-point scale. Statistical analysis was done using two-tailed paired t-test; Wilcoxon matched pairs ranks sum test, Mann-Whitney-U test and chi-square test as applicable. RESULTS: Of the fifty-five patients enrolled in the study (age range of 18-60 yrs, median age of 35yrs), 26 were males and twenty nine were females. They had a median duration of symptoms for 4 weeks. Twenty-seven patients received itopride and 28 received domperidone. One patient did not follow up in the domperidone group, thus 54 patients were evaluable for analysis. Moderate to complete symptomatic relief was observed in 22 (81%) patients in the itopride group and 19 patients (70%) in the domperidone group (p > 0.05, NS). Both the drugs were well tolerated and neither caused prolongation of QT interval nor any abnormality in any serum biochemistry values. CONCLUSION: Therapy with itopride resulted in good symptomatic relief, was safe, well tolerated and comparable in efficacy to domperidone in relieving the symptoms of NUD. By virtue of its efficacy and tolerability, it could be an ideal choice for providing symptomatic relief to patients suffering from non-ulcer dyspepsia.

Eficácia e tolerabilidade da moclobemida em dois regimes terapêuticos no tratamento de episódios depressivos maiores / Efficacy and tolerability of moclobemide in two therapeutic regimens for treatment of major depressive episodes

O antidepressivo moclobemida, da classe das benzamidas, exerce seus efeitos farmacológicos e químicos por inibiçäo predominante da monoaminoxidase A. Seu espectro de atividade antidepressiva é mais amplo e a interaçäo com a tiramina é muito menor que a dos IMAOs clássicos. Dados preliminares sugeriam que a droga apresentava eficácia comparável em regime de administraçäo três ou duas vezes ao dia, sendo a melhor tolerabilidade nesse último regime terapêutico. Em estudo aberto prospectivo e randomizado, compararam-se esses regimes terapêuticos em paciente adultos, dos sexos masculino e feminino, com episódios depressivos maiores de acordo com definiçäo dos DSM-III-R. O protocolo, aprovado pelo Comitê de Ética em Pesquisa das intituiçöes, obedeceu as normas da Declaraçäo de Helsinque-Tóquio-Veneza-Hong-Kong com consentimento escrito, após informaçäo, de todos os pacientes participantes. As doses utilizadas foram 300-450mg/dia e a duraçäo do tratamento foi de oito semanas. Os regimes terapêuticos foram: Regime BID: 300 a 450mg/dia em doses individuais, administradas pela manhä e à noite; Regime TID: 450mg em doses divididas, três vezes ao dia. A Escala de Depressäo de Hamilton e a Impressäo Clínica Global para eficácia e tolerabilidade, bem como um questionário para análise do sono foram avaliados pré-tratamento e cinco vezes durante o tratamento de 56 dias. Anamnese e exame físico, eletrocardiograma e exames de laboratório foram feitos antes e depois do tratamento. Os efeitos colaterais adversos foram avaliados em cada visita de evoluçäo (5 visitas) e os pacientes foram instruídos para procurar o serviço em qualquer ocasiäo, caso tivessem qualquer intercorrência. Näo houve qualquer restriçäo da dieta alimentar. Foram incluídos 64 pacientes, ambulatoriais, com idades entre 18 e 63 anos, com média de 38,6. Trinta e quatro pacientes foram incluídos no Regime BID e 30 no Regime TID, sendo que näo houve qualquer diferença demográfica expressiva entre os grupos. A média da soma de escores da Escala de Hamilton antes do tratamento foi de 34,3 ñ 3,6 BID e 34,1 ñ 4,0 no regime TID. A eficácia da moclobemida näo diferiu significativamente no tratamento BID e TID