Study type |
Outcome |
Exemplar study |
Threats to validity from study design |
Specific |
General |
Observational studies |
Aspirin |
Hepatocellular carcinoma |
Simon 2020 |
Implausible 50% absolute risk reduction, largely non‐cirrhotic cohort |
Retrospective cohort |
Administrative data |
Confounding by indication |
Immortal time bias |
Beta‐blockers |
Hepatocellular carcinoma |
Wijarnpreecha
94
|
Implausible 39% relative risk reduction |
Statins |
Variceal bleeding |
Mohanty
99
|
Low event rates (1%–2%) |
Ascites |
Unreliable diagnostic codes |
Hepatocellular carcinoma |
Simon
100
|
Implausible 70% absolute risk reduction |
Largely non‐cirrhotic cohort |
Hepatic encephalopathy |
Tapper
98
|
Did not use new‐user design |
|
Randomised trials |
Carvedilol |
|
Variceal bleeding |
Sinagra 2014 (meta‐analysis of RCTs)
163
|
Optimal method of patient selection unknown |
None |
Ascites |
Villaneuva 2018
91
|
Highly adherent patients; most with viral untreated hepatitis C |
|
Statins |
Mortality |
Abraldes
97
|
Small sample (N = 158) powered to detect the difference in bleeding but not mortality |
All patients were on Non‐selective Beta‐Blockers |