Exportation of unethical practices to low and middle income countries in biomedical research / Exportación de prácticas éticas deficientes de investigación biomédica hacia países con menor grado de desarrollo

Substandard ethical practices in biomedical research have been exported from more developed countries to less developed countries worldwide. The term for this practice is called ethics dumping, which can be described as exporting, in clinical research, sensitive ethical practices from more developed to less developed countries, with subpar requirements and other economic or operational advantages that would be inadmissible in developed countries. Examples for this practice are described, as well as its origin, receptivity, and perpetuation, together with some preliminary guidance and advice in order to work towards possible solutions for this ethically sensitive issue in the future

En la investigación biomédica se han exportado prácticas éticas deficientes desde los países con mayor grado de desarrollo hacia países con menor grado de desarrollo a nivel mundial. El término para esta práctica es el de deposición de prácticas éticas («Ethics Dumping»), que puede describirse como el hecho de exportar, en la realización de investigación clínica, prácticas éticas sensibles del tipo de exigencia disminuida y otras ventajas de índole operativa y económica no aceptables en países desarrollados, hacia países no desarrollados. Se describen ejemplos de esta práctica, así como su origen, receptividad, y perpetuación, junto con algunas guías preliminares y recomendaciones, con el fin de trabajar hacia el futuro en busca de posibles soluciones para este asunto éticamente sensible

Responsabilidad profesional aplicada a la farmacovigilancia: un estudio de caso en México / Professional responsibility applied to drug surveillance: a study case in México / Responsabilidade profissional aplicada à farmacovigilância: um estudo de caso no México

El sistema internacional de farmacovigilancia recopila información sobre eventos adversos por medicamentos a partir de informes emitidos por los médicos en la práctica clínica. Los reportes de reacciones adversas a medicamentos (RAM) son escasos. Diseñamos un cuestionario basado en una escala de Likert de cinco puntos. El cuestionario, de 24 preguntas, se administró a una muestra de médicos. Las respuestas de los cuestionarios indican que es importante contar con sistemas de farmacovigilancia. A pesar de ello, casi tres cuartos de los encuestados no sabían cómo informar de una reacción adversa y dos quintos no deseaban hacerlo. Tres cuartas partes de los encuestados expresaron que la instrucción sobre la elaboración de informes debería comenzar durante la carrera de Medicina. Los resultados sugieren que la elaboración de informes de RAM debe incluirse en la educación médica. Es necesario establecer protocolos que aseguren que los lineamientos para informar RAM sean fáciles de seguir. Es recomendable que los programas de capacitación y educación médica continua generen una conciencia de responsabilidad frente al reporte de RAM.

The international pharmacovigilance system collects adverse drug events reported by physicians in their clinical practice. Adverse drug reactions (ADR) reported are scarce. We designed a questionnaire based on a 5-point Likert scale. The questionnaire (24 questions) was administered to a sample of physicians in Mexico City. Questionnaire responses indicated that having pharmacovigilance systems is important. Despite this, nearly three quarters of respondents did not know how to report an adverse drug reaction, and two-fifths were not willing to do so. Three quarters believed that education regarding reporting and its methods should be initiated during medical school. The results from our questionnaire suggest that medical school training in ADR report writing should be implemented. Good protocols have to be in place to ensure that ADR report forms have easy-to-follow guidelines and are easy to complete. It is recommended that the programs of training and medical education generate conscience of responsability towards the report of ADRs.

O sistema internacional de farmacovigilância recopila informação sobre eventos adversos por medicamentos a partir de informes emitidos pelos médicos na prática clínica. Os informes de reações adversas a medicamentos (RAM) são escassos. Idealizamos um questionário baseado numa escala de Likert de cinco pontos. O questionário, de 24 perguntas, foi administrado a uma mostra de médicos. As respostas dos questionários indicam que é importante contar com sistemas de farmacovigilância. Apesar disso, quase três quartos dos entrevistados não sabiam como informar uma reação adversa e dois quintos não desejavam fazê-lo. Três quartas partes dos entrevistados expressaram que a instrução sobre a elaboração de informes deveria começar durante o curso de Medicina. Os resultados sugerem que a elaboração de informes de RAM deve ser incluido na educação médica. É necessário estabelecer protocolos que assegurem que as orientações para informar RAM sejam fáceis de seguir. É recomendável que os programas de capacitação e educação médica contínua gerem uma consciência de responsabilidade frente ao informe de RAM.

Bioavailability of two oral-tablet and two oral-suspension formulations of naproxen sodium/paracetamol (acetaminophen): single-dose, randomized, open-label, two-period crossover comparisons in healthy Mexican adult subjects.

BACKGROUND: Naproxen sodium/paracetamol (acetaminophen) is a combination for the treatment of symptomatic pain and fever marketed both as a prescription and an over-the-counter product in Mexico. OBJECTIVE: The aim of these 2 studies was to compare the bioavailability and to determine the bioequivalence of 2 test formulations (an oral-tablet formulation containing the combination of naproxen sodium/paracetamol 275/300 mg and an oral-suspension formulation containing the combination of naproxen sodium/paracetamol 375/300 mg per 15 mL) with their corresponding listed reference-drug formulations in Mexico (a list issued by Mexican health authorities). METHODS: Two separate, single-dose, randomized, open-label, 2-period crossover, postmarketing studies were conducted. For each study, a different set of eligible subjects was selected comprising healthy Mexican adults of either sex, and subjects were randomly assigned to receive 1 test formulation of the combination of naproxen sodium/paracetamol followed by the corresponding reference-drug formulation, or vice versa, with a 1-week washout period between doses. After a 12-hour overnight fast, subjects received a single dose of naproxen sodium/paracetamol 275/300-mg tablet or naproxen sodium/paracetamol 375/300 mg per 15 mL suspension, depending on the study. For the analysis of pharmacokinetic parameters, including C(max), AUC from time 0 (baseline) to 48 hours (AUC(0-48)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and at 0.16, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours after administration. The formulations were considered bioequivalent if the geometric mean ratios (test/reference) of the C(max) and AUC were within the predetermined range of 80% to 125%. Tolerability was determined by clinical assessment, monitoring vital signs, laboratory analysis results, and subject interviews regarding adverse events. RESULTS: A total of 26 subjects (15 men, 11 women; mean [SD] age, 29 [8] years [range, 20-50 years]; weight, 63.1 [9] kg [range, 51.4-84.4 kg]; height, 164 [9] cm [range, 149-179 cm]; and body mass index [BMI], 23.53 [2.18] kg/m(2) [range, 18.54-26.82 kg/m(2)]) were enrolled to receive the suspension-dosage formulation; 13 subjects received the suspension-test formulation first. A total of 26 subjects (13 men, 13 women; mean [SD] age, 29 [8] years [range, 18-43 years]; weight, 64.3 [7.7] kg [range, 50.6-80.7 kg]; height, 165 [9] cm [range, 151-181 cm]; and BMI, 23.64 [2.43] kg/m(2) [range, 18.02-26.42 kg/m(2)]) were enrolled to receive the tablet-dosage formulation; 13 subjects received the tablet-test formulation first. No significant period or sequence effects were detected based on analysis of variance. For the suspension-dosage formulation, the 90% CIs for naproxen C(max), AUC(0-48), and AUC(0-infinity) were 93.06% to 104.00%, 93.50% to 98.44%, and 92.14% to 98.99%, respectively, and were 90.09% to 105.90%, 88.58% to 99.34%, and 91.43% to 101.55%, respectively, for paracetamol. For the tablet-dosage formulation, the 90% CIs for naproxen C(max), AUC(0-48), and AUC(0-infinity) were 102.83% to 117.15%, 96.59% to 104.26%, and 96.01% to 102.90%, respectively, and were 94.04% to 121.09%, 95.48% to 105.64%, and 96.64% to 105.42%, respectively, for paracetamol. CONCLUSIONS: In these 2 small studies in healthy Mexican adult subjects, a single dose of naproxen sodium/paracetamol 275/300 mg of the test formulation of the tablet-dosage formulation or a single dose of naproxen sodium/paracetamol 375/300 mg per 15 mL of the test formulation of the suspension-dosage formulation was found to be bioequivalent to the corresponding reference formulations according to the regulatory definition of bioequivalence based on the rate and extent of absorption. All formulations were generally well tolerated.

Bioavailability of two oral suspension and two oral tablet formulations of acyclovir 400 mg: two single-dose, open-label, randomized, two-period crossover comparisons in healthy Mexican adult subjects.

BACKGROUND: Acyclovir is an important antiviral drug, used extensively for treatment of herpes simplex and varicella zoster. Six oral generic formulations of acyclovir are available in Mexico; however, a literature search failed to identify data information concerning the bioavailability of these formulations in the Mexican population. OBJECTIVE: The aim of these 2 studies was to compare the bioavailability of 4 oral formulations of acyclovir 400 mg--2 tablet formulations and 2 suspension formulations--with their corresponding listed drug references in Mexico (a list issued by Mexican Health Authorities). METHODS: Two separate, single-dose, open-label, randomized, 2-period crossover studies were conducted at the Centro de Estudios Científicos y Clínicos Pharma, S.A. de C.V. (clinical unit), Mexico City, Mexico. For each study, a different set of eligible subjects were selected. They included healthy Mexican volunteers of either sex. For each study, subjects were randomly assigned to receive 1 test formulation of acyclovir 400 mg followed by the reference formulation, or vice versa, with a 1-week washout period between doses. After a 12-hour (overnight) fast, subjects received a single 400-mg dose (tablet or 10-mL suspension) of the corresponding formulation. For the analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, and 24 hours after dosing. The formulations were considered bioequivalent if the natural logarithm (ln)-transformed ratios of Cmax and AUC were within the predetermined equivalence range of 80% to 125% and if P