Progress has been hampered by relatively small studies, different methods of molecular analysis, and heterogeneity in histologic subtypes, stage, treatment administered, and survival criteria used.
In the pediatric setting, most reports have been generated by relatively small studies.
3– 9 Discordance in past research may partly be explained by relatively small study samples, narrow treatment inclusion criteria (eg, surgically treated patients), varying disease inclusion criteria with respect to tumor histology and stage, and limited geographic or population coverage.
Sensitivity analyses were conducted by excluding relatively small studies and restricting analysis to good-quality studies.
Our knowledge of the extent of framing effects on patients and outcomes is limited by small numbers of relatively small studies [ 43].
However, these relatively small studies were hampered by imprecise risk estimates [ 13, 14].
While interpretations should be tempered by the relatively small study size, exploratory nature of the analysis, and use of historical controls for the rAd5 only comparison, there are a number of significant observations that merit additional investigation.
Indeed, fully evaluating the impact of different factors determining CSF exposure (plasma concentration, time of sample collection following dose, BBB dysfunction, concomitant drug administration, etc). is complex and will require a larger sample and more detailed modeling than allowed by this relatively small study.
Our findings possibly are hampered by the relatively small study population and therefore need to be interpreted with caution.
Although the results for most comparators have wide credible intervals suggesting inconclusive results, the HRs for tiotropium + salmeterol, tiotropium + SFC and beclomethasone + formoterol have particularly wide credible intervals; in each case the results are generated by single, relatively small study arms therefore the uncertainty around the estimates is high.
However, a comprehensive analysis of the predictive value of YB-1/p18 is hampered by (a) relatively small study cohort (n = 111) with a rare incidence of new malignancies, and (b) short follow-up of the very high-risk patients due to the fact that these patients received liver transplantation on average within 6-12 months after evaluation [ 34].
