Quality assessment
This study used the method in the Cochrane Handbook to assess the risk
of bias of the included studies because the quality of the study has an
important impact on the credibility of the results. A high-quality study
design can generate more reliable evidence[43, 44]. Three of the
nine included studies had a low risk of bias, while the others were
unclear. Although there were no studies with a high risk of bias, four
RCTs with an unclear risk of bias were identified due to reporting
ambiguous details, especially for blinding and random sequence
generation procedures. Alternatively, the three RCTs with a low risk of
bias explained their procedures for generating random sequences using
computer software or random number tables and reported blinded
participants or researchers. These important methodological designs
improved the validity and reliability of their results. However, some
studies did not mention the details of the methodological design and how
the trial was implemented and can, therefore, only be judged as having
an unclear risk of bias. There is no doubt that an unclear risk of bias
has the potential to be high risk, which reduces the reliability of the
evidence. Therefore, randomized controlled design trials should
emphasize reporting study design features such as randomization and
blinding.
As for the certainty of the evidence, the GRADE results showed that
Varenicline was very low, Naltrexone was moderate, and Topiramate and
Bupropion were low. Considering that all the included studies were RCTs,
only five degradation factors were considered. Among these factors, high
heterogeneity (inconsistency), wide confidence intervals (imprecision),
and low quality or a small number of included studies reduced the level
of evidence. Especially for Varenicline and Topiramate, their high
heterogeneity reduced the certainty of the evidence. The extent of the
downgrade was based on the degree of heterogeneity, such that if
heterogeneity was less than 50%, the study was downgraded one level,
otherwise downgrading by two levels was considered. The number of
studies was also assessed as it would have an impact on the certainty of
the evidence. The drugs in this systematic review only had a few studies
each, especially for Topiramate and Bupropion, and as such, the level of
evidence was reduced due to the small number of studies.