TY - JOUR
T1 - The Fragility Index in a Cohort of HIV/AIDS Randomized Controlled Trials
AU - Wayant, Cole
AU - Meyer, Chase
AU - Gupton, Rebecca
AU - Som, Mousumi
AU - Baker, Damon
AU - Vassar, Matt
N1 - Publisher Copyright:
© 2019, Society of General Internal Medicine.
PY - 2019/7/15
Y1 - 2019/7/15
N2 - HIV/AIDS is associated with significant morbidity, mortality, and financial burden. For these reasons, robust clinical evidence is critical. We aim to investigate the fragility index, fragility quotient, and risk of bias of clinical trial endpoints in HIV medicine. The fragility index represents the minimum amount of trial endpoint “nonevents” changed to “events” in one trial arm required to nullify statistical significance. The fragility quotient contextualized the fragility index by dividing the index by the total trial sample size. We selected eligible trials from the Department of Health and Human Services guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents. We calculated the fragility index and fragility quotient for all included trials. The Cochrane “risk of bias” Tool 2.0 was used to evaluate the likelihood and sources of bias in the included trials. Thirty-nine RCTs were included for our analysis of fragility. Thirty-six were included for our analysis of the risk of bias. The median fragility index was 5. Three RCTs were at high risk of bias, all due to the selection of the endpoint or statistical test. Twenty had some concerns for risk of bias. The analyzed HIV medicine RCT endpoints were fragile, overall. This indicates that a median of 5 patients across all included studies would nullify the statistical significance of the endpoints. Furthermore, we found evidence that concerns for bias are present at a high rate.
AB - HIV/AIDS is associated with significant morbidity, mortality, and financial burden. For these reasons, robust clinical evidence is critical. We aim to investigate the fragility index, fragility quotient, and risk of bias of clinical trial endpoints in HIV medicine. The fragility index represents the minimum amount of trial endpoint “nonevents” changed to “events” in one trial arm required to nullify statistical significance. The fragility quotient contextualized the fragility index by dividing the index by the total trial sample size. We selected eligible trials from the Department of Health and Human Services guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents. We calculated the fragility index and fragility quotient for all included trials. The Cochrane “risk of bias” Tool 2.0 was used to evaluate the likelihood and sources of bias in the included trials. Thirty-nine RCTs were included for our analysis of fragility. Thirty-six were included for our analysis of the risk of bias. The median fragility index was 5. Three RCTs were at high risk of bias, all due to the selection of the endpoint or statistical test. Twenty had some concerns for risk of bias. The analyzed HIV medicine RCT endpoints were fragile, overall. This indicates that a median of 5 patients across all included studies would nullify the statistical significance of the endpoints. Furthermore, we found evidence that concerns for bias are present at a high rate.
KW - HIV
KW - acquired immunodeficiency syndrome
KW - fragility index
KW - fragility quotient
KW - randomized controlled trials
UR - http://www.scopus.com/inward/record.url?scp=85065170989&partnerID=8YFLogxK
U2 - 10.1007/s11606-019-04928-5
DO - 10.1007/s11606-019-04928-5
M3 - Article
C2 - 31037544
AN - SCOPUS:85065170989
SN - 0884-8734
VL - 34
SP - 1236
EP - 1243
JO - Journal of General Internal Medicine
JF - Journal of General Internal Medicine
IS - 7
ER -