While the "gold standard" for medical trials is the randomised, double-blind, placebo-controlled trial, the African trials suffered [a number of serious problems] including problematic randomisation and selection bias, inadequate blinding, lack of placebo-control (male circumcision could not be concealed), inadequate equipoise, experimenter bias, attrition (673 drop-outs in female-to-male trials), not investigating male circumcision as a vector for HIV transmission, not investigating non-sexual HIV transmission, as well as lead-time bias
, supportive bias (circumcised men received additional counselling sessions), participant expectation bias, and time-out discrepancy (restraint from sexual activity only by circumcised men).
Lead-time bias "extend[s] the statistical length of a patient's survival without necessarily prolonging the duration of life," according to the late Alvan R.
Lead-time bias accounts for much of the illusory "improvement" seen over the last few decades in treating breast, prostate, and a few other kinds of cancer wherein the patient population has increased greatly.
Histopathologic extent of CIN 3 lesions in ALTS: implications for subject safety and lead-time bias
Cervical and central nervous system cancers increased in this group, although the increase in cervical cancer could be due to lead-time bias
in women with more monitoring.
Researchers opposed to early therapy highlight the side effect profile and often point to the lead-time bias
that this represents.
This study is subject to more serious biases that are associated with non-randomized screening studies: lead-time bias
and length bias.
3) Both studies showed earlier detection and longer survivorship of lung cancer among screened vs nonscreened groups due to lead-time bias
(because the cancer was detected earlier from screening vs clinical diagnosis, it falsely appears to prolong survival).
1) A trend toward detecting more localized cancers and a possible decreasing mortality rate from CaP in all men may be related to PSA testing, lead-time bias
, or both.