Publicação
Benefit-risk assessment of medicines: a contribution for evidence-based decisions using the number needed to treat to benefit or to harm
| Resumo: | The assessment of benefit-risk ratios is performed during the entire life-cycle of medicines. Although pre-marketing randomized controlled clinical trials provide important evidence about benefits and harms of medicines in well-defined populations, they have few intrinsic limitations. Those studies are usually underpowered to detect rare and/or long term latency adverse events. Then, serious safety problems may be identified only during post-marketing, namely by means of observational studies or spontaneous reporting schemes. Regulatory authorities closely monitor post-marketing safety signals, aiming to assure that only medicines with favourable benefit-risk ratios are available for use. When regulatory authorities conclude that the benefits no longer outweigh the risks of a medicine, they initiate actions in order to protect public health. There are several examples of medicines that were recently suspended or withdrawn from market because of safety problems. However, different regulatory authorities may reach divergent conclusions about the benefit-risk ratio of a medicine despite analysing the same evidence. One of the reasons may be the fact that the assessments still rely heavily on expert opinions and subjective qualitative weighing of the available evidence. Therefore, several projects have been initiated aiming at testing and developing methodologies that could potentially bring clarity to the decision-making process and help regulatory authorities to make more objective, consistent and evidence-based decisions. The introduction of structured frameworks that could encompass quantitative or semi-quantitative methodologies was advocated. The number needed to treat (NNT) is one of the methodologies recommended for testing in benefit-risk assessments. This project was carried out to evaluate the potential usefulness of the NNT as quantitative metric for post-marketing benefit-risk assessment of medicines, using several case studies and addressing both regulatory and clinical perspectives. There is limited evidence about the usefulness of this metric to support regulatory decisions on benefit-risk assessment. The NNT can be effectively used to quantity benefits and risks of medicines, as well as to provide additional and useful information about the magnitude of treatment effects. From a regulatory perspective, the use of the NNT may be considered only within defined structured frameworks for benefit-risk assessment, because there are several issues weighing in the assessments that are not addressed by quantitative metrics. The application of the NNT can be problematic for weighing multiple benefits and risks with different clinical relevance. Nonetheless, whenever calculable, the NNT may be used in the benefit-risk assessment of medicines, as this metric can help to strengthen regulatory decisions. In addition, the NNT is useful for supporting informed clinical decision-making, as long as it is properly calculated. In conclusion, although the NNT does not replace other evaluations in the benefit-risk assessment of marketed medicines, it provides useful information, as well as added value in well-defined assessments. |
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| Autores principais: | Mendes, Diogo Manuel de Jesus |
| Assunto: | Pharmacoepidemiology Pharmacovigilance Benefit–risk assessment Evidence-based medicine Number Needed to Treat |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | The assessment of benefit-risk ratios is performed during the entire life-cycle of medicines. Although pre-marketing randomized controlled clinical trials provide important evidence about benefits and harms of medicines in well-defined populations, they have few intrinsic limitations. Those studies are usually underpowered to detect rare and/or long term latency adverse events. Then, serious safety problems may be identified only during post-marketing, namely by means of observational studies or spontaneous reporting schemes. Regulatory authorities closely monitor post-marketing safety signals, aiming to assure that only medicines with favourable benefit-risk ratios are available for use. When regulatory authorities conclude that the benefits no longer outweigh the risks of a medicine, they initiate actions in order to protect public health. There are several examples of medicines that were recently suspended or withdrawn from market because of safety problems. However, different regulatory authorities may reach divergent conclusions about the benefit-risk ratio of a medicine despite analysing the same evidence. One of the reasons may be the fact that the assessments still rely heavily on expert opinions and subjective qualitative weighing of the available evidence. Therefore, several projects have been initiated aiming at testing and developing methodologies that could potentially bring clarity to the decision-making process and help regulatory authorities to make more objective, consistent and evidence-based decisions. The introduction of structured frameworks that could encompass quantitative or semi-quantitative methodologies was advocated. The number needed to treat (NNT) is one of the methodologies recommended for testing in benefit-risk assessments. This project was carried out to evaluate the potential usefulness of the NNT as quantitative metric for post-marketing benefit-risk assessment of medicines, using several case studies and addressing both regulatory and clinical perspectives. There is limited evidence about the usefulness of this metric to support regulatory decisions on benefit-risk assessment. The NNT can be effectively used to quantity benefits and risks of medicines, as well as to provide additional and useful information about the magnitude of treatment effects. From a regulatory perspective, the use of the NNT may be considered only within defined structured frameworks for benefit-risk assessment, because there are several issues weighing in the assessments that are not addressed by quantitative metrics. The application of the NNT can be problematic for weighing multiple benefits and risks with different clinical relevance. Nonetheless, whenever calculable, the NNT may be used in the benefit-risk assessment of medicines, as this metric can help to strengthen regulatory decisions. In addition, the NNT is useful for supporting informed clinical decision-making, as long as it is properly calculated. In conclusion, although the NNT does not replace other evaluations in the benefit-risk assessment of marketed medicines, it provides useful information, as well as added value in well-defined assessments. |
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Atividades financiadas
Não foram encontrados projetos financiados.