Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction / Implicaciones éticas, legales y económicas de la sustitución de las coformulaciones antirretrovirales a dosis fijas tomadas una vez al día por sus componentes por razones de reducción de coste

The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation

La disponibilidad de lamivudvina genérica en el actual contexto de crisis económica ha sacado a la luz una nueva discusión en los países europeos: la sustitución de las combinaciones antirretrovirales a dosis fijas tomadas una vez al día (CADF) de efavirenz/tenofovir/emtricitabina, tenofovir/emtricitabina o abacavir/lamiduvina, con la finalidad de administrar sus componentes por separado, lo que supone permitir el uso de lamivudina genérica en lugar de la emtricitabina o la lamivudina de marca. Se revisan las implicaciones legales, éticas y económicas de esta estrategia potencial, en particular en aquellos pacientes que tienen un régimen de una única pastilla una vez al día. Un cambio no consensuado en el tratamiento antirretroviral, pasando de una CADF exitosa y cómoda para el paciente a un tratamiento más complejo que incluya los componentes por separado para permitir la sustitución de uno (o varios) de ellos por los genéricos (en ausencia de una CADF genérica bioequivalente) podría ser discriminatorio porque no garantiza el acceso a un igual tratamiento de excelencia a todos los ciudadanos. Además, podría violar el principio de no maleficencia, causando potencialmente daño tanto a nivel individual (dificultando la adherencia y favoreciendo el fracaso y la resistencia al tratamiento) como a nivel comunitario (dificultando el control de la trasmisión de la enfermedad y la transmisión del VIH-1 resistente). Reemplazar una CADF por los componentes individuales de dicha combinación únicamente debería estar permitido cuando la medicación de sustitución tenga la misma composición cualitativa y cuantitativa en sus ingredientes activos, forma farmacéutica, método de administración, dosis y presentación que el medicamento que va a ser reemplazado, y cuando un estudio aleatorizado haya demostrado su no inferioridad. Por último, un estricto estudio farmacoeconómico apoyando este cambio, comparando la efectividad y el coste de una intervención específica con la mejor alternativa disponible, debería llevarse a cabo antes de su potencial implementación

Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation.

Generic and therapeutic substitutions: are they always ethical in their own terms?

Cost containment-driven drug substitution, whether generic or therapeutic, is defined as switching to another drug because it is cheaper. So far, such substitutions have drawn their public legitimacy from the general belief that they would not compromise the clinical interests of patients and certainly not violate their right to decline them if they did. This article does not enter the debate on whether or not such substitutions must give exclusive priority to the patient's interests and choices in order to be ethical. Indeed, it acknowledges the plurality of views on this matter. It simply argues that when such substitutions involve a cheaper drug that is known to have different effects and side effects, or even a drug whose effects and side effects are unknown, they are potentially deleterious to the patient, and that no competent and well-informed patient would ever consent to them. Such substitutions are thus unethical in their very own terms.