1/ What are 3 Qs you can ask yourself when looking at non-inferiority trials?
Q1) Was the trial planned i.e. pre-specified as comparing an intervention which is non-inferior to control?
WHY?
Bc changing the analysis *afterwards* introduces bias #StatswithCoreIM
2/ Q2) was the control treatment administered to the full std of care?
The trial relies on strict adherence to full standard of care for the control arm, otherwise the whole confidence interval shifts with a relative⬆️in benefit of the intervention compared to control
3/ Q3) Did investigators perform both a per protocol and intention to treat analysis?
Per protocol:
Exaggerates group difference when intervention is inferior
Less likely to result in false positive
Intention to treat:
Makes groups prognostically 🟰
Benefit of randomization
But first, take a look at this figure for what superiority trials aim to assess: What’s better?
2/ So how are NON-inferiority trials different?
They ask if a treatment is much worse than standard of care.
3/ Let’s look at the possible outcomes of a non-inferiority trial.
✔️Superior and non-inferior
✔️Non-inferior
✔️Not non-inferior
✔️Inferior and not non-inferior
✔️Inferior and non-inferior
What would you tell this patient who inquires about lab cancer #screening test to help him “live longer”?
What types of bias can occur in determining whether a cancer screening test reduces mortality?
2/ Take a look at the bolded arrows below that illustrate that early detection doesn’t always mean better outcomes!
Length-time bias applies to slow-growing disease in which patients have a long phase without symptoms.
3/ Lead time bias applies to situations where patients are screened earlier, so they are diagnosed earlier, so they appear to live longer solely by nature of knowing they have the disease for a longer period of time.
We wanted to use this opportunity to shed light on the discussion on post-menopausal hormone therapy (HT) via highlighting the important yet controversial WHI trial
2/ WHI followed the Nurses' Health Study, a prospective investigation that showed HT was associated with decreased cardiovascular disease (CVD) risk
3/ WHI, a randomized controlled trial (RCT), was believed to mitigate the effects of confounding factors better than cohort studies. WHI, in contrast to the Nurses’ Health Study, showed that HT was associated with a slightly increased risk for CVD among other conditions