Figure 2. Selecti<strong>on</strong> process 21
Initially, we planned to limit efficacy evidence to r<strong>and</strong>omized c<strong>on</strong>trolled trials (RCTs) comparing milk thistle with placebo, no milk thistle, or another active agent. Ultimately, we included evidence from prospective placebo-c<strong>on</strong>trolled trials or cohort studies for several reas<strong>on</strong>s. First, there were scant data, <strong>and</strong> it was thought that evidence from studies other than r<strong>and</strong>omized trials might provide useful preliminary informati<strong>on</strong>. Sec<strong>on</strong>d, several reportedly “r<strong>and</strong>omized” trials had dissimilar numbers <strong>of</strong> subjects am<strong>on</strong>g the study arms, raising the possibility that they were not r<strong>and</strong>omized <strong>and</strong> not <strong>of</strong> significantly different quality than other prospective c<strong>on</strong>trolled studies. The search for evidence was not repeated at the point that selecti<strong>on</strong> criteria were broadened, because the search had been designed to detect all studies <strong>of</strong> milk thistle regardless <strong>of</strong> their design. Data Abstracti<strong>on</strong> Process Two independent pers<strong>on</strong>s with clinical <strong>and</strong> methodologic expertise abstracted data; they were not blinded either to study titles or to authors’names. Previous research indicates such blinding does not enhance validity <strong>of</strong> results, <strong>and</strong> it is time <strong>and</strong> labor intensive to prepare fully masked publicati<strong>on</strong>s. 55 Items related to the internal validity <strong>of</strong> studies that were assessed included whether the trial was r<strong>and</strong>omized, adequacy <strong>of</strong> r<strong>and</strong>omizati<strong>on</strong> (method <strong>and</strong> c<strong>on</strong>cealment <strong>of</strong> assignment), whether the trial was single or double blind, whether interventi<strong>on</strong> <strong>and</strong> c<strong>on</strong>trol groups were adequately matched, identificati<strong>on</strong> <strong>of</strong> cointerventi<strong>on</strong>s such as diet or other medicati<strong>on</strong>s, <strong>and</strong> the number <strong>of</strong> dropouts. Disagreements in abstracti<strong>on</strong>s were resolved by c<strong>on</strong>sensus. Formal quality scores were not d<strong>on</strong>e because <strong>of</strong> c<strong>on</strong>troversy as to how to h<strong>and</strong>le <strong>and</strong> weight such scores statistically. Elements <strong>of</strong> study quality are given in the evidence tables. If not known, then no informati<strong>on</strong> or “not given” is noted in the evidence tables. After the abstracti<strong>on</strong> training phase, no further reliability assessment was c<strong>on</strong>ducted. One research nurse <strong>and</strong> <strong>on</strong>e physician with expertise in methodology abstracted studies addressing adverse effects. Items addressing adverse effects that were abstracted included study design (case report, case series, case c<strong>on</strong>trol, cohort, c<strong>on</strong>trolled trial) <strong>and</strong> type <strong>of</strong> specific adverse effect. Several explicit criteria aimed at assessing drug adverse effect causality were assessed, including appropriate temporal relati<strong>on</strong>ship, lack <strong>of</strong> apparent alternative causes, known toxic c<strong>on</strong>centrati<strong>on</strong>s <strong>of</strong> the drug at the time <strong>of</strong> the appearance <strong>of</strong> the symptom, disappearance <strong>of</strong> the symptom with drug disc<strong>on</strong>tinuati<strong>on</strong>, dose-resp<strong>on</strong>se relati<strong>on</strong>ship, <strong>and</strong> reappearance <strong>of</strong> the symptom if the drug was readministered. 56 Unpublished Data For reports published as abstracts, we excluded those for which we were unable to identify a complete subsequent publicati<strong>on</strong> by a repeat search <strong>of</strong> MEDLINE <strong>and</strong> EMBASE for any <strong>of</strong> the abstract authors. When published studies met selecti<strong>on</strong> criteria but did not report important design features or outcome data, this unpublished informati<strong>on</strong> was requested from the authors. Data Analysis Process Data were synthesized descriptively, emphasizing methodologic characteristics <strong>of</strong> the studies, such as populati<strong>on</strong>s enrolled, definiti<strong>on</strong>s <strong>of</strong> selecti<strong>on</strong> <strong>and</strong> outcome criteria, sample sizes, adequacy <strong>of</strong> r<strong>and</strong>omizati<strong>on</strong> process, interventi<strong>on</strong>s <strong>and</strong> comparis<strong>on</strong>s, cointerventi<strong>on</strong>s, biases in 22
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Summary Table 10. Effect sizes and
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Blumenthal M (National Advisory Pan
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Fintelmann V. Zur Therapie der Fett
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Lang I, Deak G, Nekam K, et al. Hep
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Pifferi G. Silipide: A new bioavail
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Tittel G, Wagner H. High-performanc
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Appendix A. Milk <
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Z Statistic Effect Size -3.2 -1 2 0
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Feher 1990 Marcelli 1992 Trinchet 1
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Z Statistic -3.0 Buzelli 1993 2 0 -
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