Comparação entre a associação de cobimetinibe e vemurafenibe e outras opções terapêuticas para o tratamento de melanoma metastático com mutação BRAFV600: número necessário para tratar (NNT) / Number needed to treat (NNT) comparison between the association of cobimetinib and vemurafenib among other treatment options for metastatic melanoma with brafv600 mutation

Objetivo: O objetivo do estudo foi estimar e comparar o número necessário para tratar (NNT) entre a associação de cobimetinibe + vemurafenibe e outras opções terapêuticas no tratamento de melanoma metastático BRAFV600 mutado em primeira linha. Métodos: O NNT foi calculado como o inverso do risco absoluto de um medicamento em um ponto específico de tempo (12 meses). Os comparadores considerados foram o vemurafenibe monoterapia, dabrafenibe monoterapia, dabrafenibe + trametinibe, nivolumabe e ipilimumabe. O desfecho considerado foi a sobrevida livre de progressão (SLP), cujas curvas foram obtidas dos estudos coBRIM, BRIM-3, Robert, 2015, BREAK-3 e Checkmate 67. Resultados: Em 12 meses, os resultados de NNT foram: cobimetinibe + vemurafenibe = 1,92, vemurafenibe = 3,33; dabrafenibe = 4,67; dabrafenibe + trametinibe = 2,04; nivolumabe = 4,39 e ipilimumabe = 7,84. Conclusão: A associação de cobimetinibe e vemurafenibe no tratamento de pacientes com melanoma irressecável ou metastático, positivo para mutação BRAFV600 sem tratamento sistêmico prévio para a doença, apresenta resultados favoráveis em termos de NNT quando comparada a todas as outras opções terapêuticas disponíveis no mercado brasileiro para essa mesma indicação.

Objective: The objective of the study was to estimate and compare the number needed to treat (NNT) between the association of cobimetinib + vemurafenib and other therapeutic options in the first line treatment of metastatic melanoma with BRAFV600 mutation. Methods: The NNT was calculated as the inverse of absolute risk of a drug in a specific time point (12 months). The considered comparators were vemurafenib (monotherapy), dabrafenib (monotherapy), dabrafenib + trametinib, nivolumab and ipilumumab. Progression free survival (PFS) was the defined outcome, and its curves were obtained from coBRIM, BRIM-3, BREAK-3, Robert, 2015 and Checkmate 67 studies. Results: In 12 months, the NNT results were: cobimetinib + vemurafenib = 1.92; vemurafenib = 3.33; dabrafenib = 4.67; dabrafenib + trametinib = 2.04; nivolumab = 4.39 and ipilimumab = 7.84. Conclusion: The association of cobimetinib and vemurafenib in the treatment of patients with unresectable or metastatic melanoma, BRAFV600 mutated without previous systemic treatment, showed favorable results in terms of NNT when compared to the other therapeutic options available in the Brazilian market for the same indication.

Número necessário a tratar (NNT) e custo por evento evitado (COPE) de enzalutamida e acetato de abiraterona para o tratamento de câncer de próstata resistente à castração que falharam a terapia de privação de androgênio / Number needed to treat (NNT) and cost of preventing an event (COPE) of enzalutamide vs. abiraterone acetate plus prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients who failed androgen deprivation therapy (ADT)

Objetivo: O objetivo deste estudo foi estimar o número necessário a tratar (NNT) e custo por evento evitado (COPE) de enzalutamida (ENZ) em comparação com abiraterona+prednisona (AA+P) em 12 e 24 meses sob perspectiva do sistema de saúde suplementar em pacientes com câncer de próstata resistente à castração metastático (CPRCM) sem quimioterapia prévia. Métodos: O NNT é calculado pelo inverso da diferença do risco absoluto de uma intervenção versus placebo; adicionalmente, o COPE representa o NNT multiplicado pelo custo de tratamento total de um período determinado. O risco absoluto de ENZ e AA+P e seus respectivos controles foram obtidos das curvas de sobrevida livre de progressão radiográfica (SLPr) e sobrevida global (SG) dos estudos PREVAIL e COU-AA-302, respectivamente. A duração de tratamento média no horizonte de 24 meses foi estimada utilizando a área sob a curva das respectivas curvas de SLPr. Os resultados foram a comparação entre ENZ e AA+P versus seus respectivos placebos em 12 e 24 meses para NNT e COPE. O custo total de tratamento consistiu em custos de medicamento, monitoramento, e manejo de eventos adversos (≥1%, eventos de interesses especiais). Resultados: A análise de 12 meses resultou em NNTSG/ENZ= 12,79; NNTSLPr/ENZ= 2,59; NNTSG/AA+P= 116,28; NNTSLPr/AA+P= 4,72 e COPESG/ENZ= BRL 1.626.583; COPESLPr/ENZ= BRL 329.701; COPESG/AA+P= BRL 15.144.886; COPESLPr/AA+P= BRL 614.368. Para a análise de 24 meses, os resultados foram: NNTSG/ENZ= 11,00; NNTSLPr/ENZ= 3,58; NNTSG/AA+P= 16,56; NNTSLPr/AA+P= 5,00 e COPESG/ENZ= BRL 1.965.454; COPESLPr/ENZ= BRL 639.327; COPESG/AA+P= BRL 2.833.580; COPESLPr/AA+P= BRL 855.741. Conclusão: Para ambos horizontes de tempo, os resultados foram favoráveis para ENZ vs. AA+P em pacientes com CPRCM.

Objective: The aim of this study was to estimate the NNT and COPE of enzalutamide (ENZ) in comparison with abiraterone acetate+prednisone (AA+P) over a 12-month and 24-month period from the Supplementary Health System perspective in metastatic castration-resistant prostate cancer patients who are chemotherapy naïve (MCRPC). Methods: The NNT is calculated by the inverse of the absolute risk reduction of an intervention vs. control; additionally, COPE represents the NNT multiplied by total cost of treatment in a pre-defined period. The absolute risk of ENZ and AA+P, and their respective control treatments, were obtained from the Kaplan Meier curves for the co-primary end points of radiographic progression free survival (rPFS) and overall survival (OS) from the clinical studies PREVAIL and COU-AA-302, respectively. Mean treatment duration was estimated utilizing the area under curve (AUC) technique from the respective intervention rPFS curves. The results analyzed ENZ or AA+P versus its respective placebo at 12 and 24 months for NNT and COPE. Total treatment cost consisted of drug cost, monitoring cost and adverse event (>=1% incidence and special interest adverse events) related cost. Results: The 12 month analysis resulted in NNTOS/ENZ= 12.79; NNTrPFS/ENZ= 2.59; NNTOS/AA+P= 116.28; NNTrPFS/AA+P= 4.72 and COPEOS/ENZ= BRL 1,626,583; COPErPFS/ENZ= BRL 329,701; COPEOS/AA+P= BRL 15,144,886; COPErPFS/AA+P= BRL 614,368. For the 24-month analysis, the results were: NNTOS/ENZ= 11.00; NNTrPFS/ENZ= 3.58; NNTOS/AA+P=16.56; NNTrPFS/AA+P= 5.00 and COPEOS/ENZ= BRL 1,965,454; COPErPFS/ENZ= BRL 639,327; COPEOS/ AA+P= BRL 2,833,580; COPErPFS/AA+P= BRL 855,741. Conclusion: Across the 12- and 24-month time horizons, the NNT and COPE was favorable for ENZ vs. AA+P in patients with MCRPC.

Relative Impact of the 2012 SSC Guideline Recommendations under the Scope of Numbers Needed to Treat (NNTs).

The surviving sepsis campaign (SSC) guidelines aimed to reduce mortality in severe sepsis and septic shock. The present study was performed to find out which and how many recommendations of the 2012 SSC update were based on significant effects from clinical studies in adult patients with severe sepsis and septic shock, leading to numbers needed to treat (NNTs). Every reference of the SSC 2012 guideline regarding clinical trials in adult patients was screened for absolute risk reduction regarding mortality to calculate NNTs. 17 relevant clinical trials out of 338 were identified. The NNTs ranged between 3.55 to 23.24. Significant reductions of mortality were detected, and items recommended in the SSC guidelines regarding early goal directed therapy (EGDT)/standard operating procedures (SOP)/sepsis bundles, early therapy with antibiotics, combined antibiotic therapy, and use of norepinephrine. Therapy with norepinephrine and the 6h bundles revealed the lowest NNTs. Significant reductions in mortality with restricted or no recommendations regarded therapy with hydrocortisone, therapy with highdose antithrombin III, and enteral feeding with eicosapentaenoic acid, gamma-linolenic acid and antioxidants. In conclusion, only a few recommendations of the 2012 SSC guidelines are based on significant beneficial effects coming from clinical trials in patients with severe sepsis and septic shock. When transferring study results and NNTs, physicians should take into account the own setting and own subgroup of patients. If feasible, costs of additional treatment success may be quantified underlying NNTs.

Probability and Distribution of the Number Needed to Treat / 医薬品情報学

<b>Objective: </b>The number needed to treat (NNT) is an index for determining the number of patients who need to be treated in order to prevent the occurrence of an adverse event when a new treatment instead of the standard one is used.<br><b>Methods: </b>The properties of NNT were examined by using the geometric distribution formula as the probability for preventing the occurrence of an adverse event in the NNT.<br><b>Results: </b>When the NNT was enlarged infinitely, the probability for the prevention of an adverse event by NNT was found to be 63.2% (=1−e⁻¹), and the number of patients who needed to show adverse event prevention at the probability of 95% was about 3 times as that of the NNT (Rule of Three).<br><b>Conclusion: </b>When the effect of new treatment needs to be evaluated based on NNT, one should take these properties of NNT into consideration.

Uma visão evidente da prática baseada em evidências na medicina perinatal: ausência de evidência não é evidência de ausência / An evident view of evidence-based pratice in perinatal medicine: absence of evidence is not evidence of absence

OBJETIVO: Proporcionar elementos valiosos e um pouco de humor nesta chamada era da "prática baseada em evidências" com o objetivo de ajudar os clínicos a fazer escolhas melhores no cuidado que eles provêem com base em evidências, e não simples ou exclusivamente com base em um ensaio clínico randomizado (ECR) ou meta-análise (o que pode não ser evidência). FONTE DOS DADOS: Livros e artigos com revisão por pares são citados e listados na bibliografia. Evidências de vida, aprendizado através de nossos próprios erros e muitos outros fatos evidentes que sustentam esta revisão não são citados. SÍNTESE DOS DADOS: 1) "Ausência de evidência não é evidência de ausência" e "falta de evidência de efeito não significa evidência de nenhum efeito". 2) Os ECR com resultado "negativo" e aqueles com resultado "positivo", mas sem os resultados importantes, muitas vezes não podem concluir o que concluem. 3) Os ensaios clínicos não-randomizados e os estudos práticos podem ser importantes. 4) A pesquisa em busca de provas é diferente da pesquisa em busca de aperfeiçoamento. 5) A escolha clínica deve avaliar os efeitos nos desfechos importantes para os pacientes e seus pais. 6) A quantificação de desfechos adversos, do número necessário para causar dano e do número necessário para tratamento não é assim tão simples. CONCLUSÕES: Desafios importantes inerentes à pesquisa em serviços de saúde devem ser correlacionados a possíveis aplicações clínicas usando ferramentas que permitam uma "visão mais clara da prática baseada em evidências" na medicina perinatal, lembrando que a ausência de evidência não é evidência de ausência.

OBJECTIVE: To provide valuable elements and some humor in this so-called era of "evidence-based practice" with the aim of helping clinicians make better choices in the care they deliver based on evidence, not simply or exclusively based on a randomized clinical trial (RCT) or meta-analysis (which may not be evidence). SOURCES: Books and peer-reviewed articles are quoted and listed in the bibliography. Evidence of life, learning from our own mistakes and many other evident facts that support this review are not quoted. SUMMARY OF THE FINDINGS: 1) "Absence of evidence is not evidence of absence" and "lack of evidence of effect does not mean evidence of no effect". 2) RCTs with "negative" results and those with "positive" results, but without outcomes that matter, often cannot conclude what they conclude. 3) Non-randomized clinical trials and practical trials may be important. 4) Research to prove is different than research to improve. 5) Clinical choice must assess effects on outcomes that matter to patients and their parents. 6) Quantifying adverse outcomes, number needed to damage and to treat is not that simple. CONCLUSIONS: Significant challenges inherent to health service research must be correlated to possible clinical applications using tools to have a more "evident view of evidence-based practice" in perinatal medicine, recalling that absence of evidence is not evidence of absence.

Some Method of Abstracting a Clinical Evidence by the Evidence-based Medicine

No abstract available.