Que tiro foi esse, na ciência?

Dias atrás fui ver se o ISCHEMIA TRIAL havia saído ou se havia previsão de publicação.

No site oficial do trial observei o endpoint primário e encontrei algo diferente de infarto e morte, aquilo que achava ser. Imediatamente questionei Luis Claudio Correia (o que gerou a publicação: ISCHEMIA Trial: mudança de regra no apagar das luzes. Concomitantemente, fui atrás de notícias e explicações (não havia nenhuma no site oficial). Absolutamente nada encontrei além de algumas trocas de mensagens informais no Twitter. Entrei numa delas, vale a pena conferir:

Percutaneous coronary intervention (#PCI) has revolutionized cardiac care for 40 years. #ORBITA follows #COURAGE: recognizing PCI does NOT reduce death or MI after #stableangina.#ReadMorehttps://t.co/KUHdoIEYmmhttps://t.co/FJWjUdfh8d pic.twitter.com/g8veV8Z76I

— Wayne Bond Lau, MD (@WBLMD) February 15, 2018

Meu próximo passo foi perguntar para responsáveis pelo trial:

"Dear Guilherme

The trial has adhered to the most rigorous clinical trial standards. Knowing that many trials are underpowered due to lower than projected event rates, the original protocol, approved by an independent NIH/NHLBI-appointed protocol review committee, pre-specified that if the aggregate event rate was lower than projected that we could convene an independent panel, at a pre-specified time, to advise the trial leadership and NHLBI regarding switching to the pre-specified 5-component endpoint and/or extending recruitment and/or follow-up. This panel was separate from the DSMB so that the recommendation would be made by experts blinded to outcomes by treatment group. For the entire trial duration, each of the 5 components of the endpoint were adjudicated centrally by independent reviewers blinded to treatment group. The aggregate event rate was lower than projected and trial leadership and NHLBI accepted the independent panel recommendation to change the primary endpoint, and extend recruitment and follow-up. This process was a deliberate, considered one, involving the trial Leadership Committee, Steering Committee, NLHBI program staff, statisticians, and independent experts and took nearly a year of planning. It was certainly not done “in the middle of the night.” The original CV death and MI endpoint remains a major secondary endpoint. We will be publishing the design paper soon, and this will be described in that manuscript.

Thanks for the opportunity to respond.

David

David J. Maron, MD, FACC, FAHA
ISCHEMIA Trial Co-Chair/PI
Stanford University School of Medicine"

Em tempos em que supostamente tanto valorizamos transparência, não encontrar a informação pública e anterior ao fato da mudança no protocolo, é algo que não compreendo. Publicar manuscrito com design do trial agora não, né?!

Não compreendo também porque o painel independente não optou por "extending recruitment and/or follow-up".

Quanto ao cegamento, é justificativa altamente questionável. Uma baixa taxa de eventos nos dois grupos e ausência de diferença, por mais que a pessoa não consiga saber qual é qual, traz LUZ, não a escuridão típica da cegueira... Muita luz!

Lembremos ainda do caso do CASINO TRIAL, onde o estudo literalmente sumiu.