Wesley Tansey writes:
That is little question one thing we each can agree is a tragic and wrongheaded use of statistics, particularly unbelievable reliance on null speculation significance testing. Here’s an example:
Part III trial. Failed as a result of their main endpoint had a p-value of 0.053 as an alternative of 0.05. Right here’s the vital precise end result information although:
For the first efficacy endpoint, INV-PFS, there was no vital distinction in PFS between arms, with 243 (84%) of occasions having occurred (stratified HR, 0.77; 95% CI: 0.59, 1.00; P = 0.053; Fig. 2a and Desk 2). The median PFS was 4.5 months (95% CI: 3.9, 5.6) for the atezolizumab arm and 4.3 months (95% CI: 4.2, 5.5) for the chemotherapy arm. The PFS charge was 24% (95% CI: 17, 31) within the atezolizumab arm versus 7% (95% CI: 2, 11; descriptive P
The percentages of atezolizumab being higher than chemo are clearly excessive. But this complete article is being written because the remedy failing just because the p-value was 0.003 too excessive.
He provides:
And these confidence intervals are primarily based on proportional hazards assumptions. However that is an immunotherapy trial the place we have now good evidence that these trials violate the PH assumption. Principally, you get toxicity early on with immunotherapy, however sufferers that survive which have a a lot better end result down the highway. Identical story right here; see determine beneath. Early on the immunotherapy sufferers are doing a bit of worse than the chemo sufferers however the long-term survival is a lot better.
As typical, our beneficial answer for the primary downside is to acknowledge uncertainty and our beneficial answer for the second downside is to increase the mannequin, on the very least by including an interplay.
Concerning acknowledging uncertainty: Sure, in some unspecified time in the future choices should be made about selecting therapies for particular person sufferers and making common medical suggestions—but it surely’s a mistake to “prematurely collapse the wave operate” right here. This can be a analysis paper on the effectiveness of the remedy, not a decision-making effort. Hold the uncertainty there; you’re not doing us any favors by appearing as in case you have certainty once you don’t.