The median OS was 9.7 and 5.7 months in groups NA and A, respectively (P = 0.0002), after adjustments for a lead-time bias
; in alcohol-abstinent and alcohol-non-abstinent groups, median OS was 5.8 and 5.0 months, respectively (P = 0.09).
Numerous flaws in these RCTs included: inadequate equipoise; researcher and participant expectation bias; selection bias; inadequate blinding; problematic randomisation; lead-time bias
; attrition bias/participants lost to follow-up; early termination; and failure to investigate non-sexual transmission--all of which exaggerated treatment effects.
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
. Cancer Epidemiol Biomarkers Prey.
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.
First, there is a substantial amount of subclinical prostate cancer; ie, prostate cancer often exists in the absence of Symptoms. Second, lead-time bias
(the apparent increase in survival time seen when a disease is diagnosed early, when such an increase is due only to the time gained by the early diagnosis) is particularly likely in the case of prostate cancer, which is known to develop slowly in many men. Third, this capability for slow growth also increases the likelihood of length-time bias, the apparent increase in survival time seen when slower growing tumors are diagnosed.