40 No 14 (54) 12 (46) 0.37 1 (33) 2 (67)   Number of enrolled patients         ≤ 1000 patients 13 (45) 16 (55)   1 (20.0) 4 (80.0) 0.06 > 1000 patients 10 (53) 9 (47) 0.60 9 (69) 4 (31)   The graphical map of MCA (Figure 2) shows that intensive follow-up procedures cluster with Western European and East Asian studies, studies with less than 50 participating centers and less than 1000 enrolled patients, and with patients enrollment beginning before 1998, while the minimal approach clusters with RCTs enrolling more than 1000 patients and beginning enrollment after 1998 (Figure 2). At multivariate regression

analysis, only geographic location of the trial was predictive for a distinct follow-up methodology (P = 0.008). In particular, setting

as a reference the international studies, Western European (P = 0.004) and East Asian studies (P = 0.010) use intensive follow-up procedures with a significantly higher frequency than international RCTs, while no differences see more are detected between North American and international RCTs. Figure 2 Multiple correspondence analysis of possible relationships among all variables. For each follow-up approach, the frequency at which the different exams are performed is highly variable, ranging from 1 to 4 times/year for history and/or physical examinations, and from 1 to 3 times/year for imaging modalities, as shown in Table 4. Almost all RCTs showed the highest number of evaluations/year in the first 1–2 years of follow-up; 5-year follow-up and annually

thereafter was chosen by almost all studies, with the following exceptions: two studies interrupted all imaging modalities at the 3rd year [83, 84]; one study discontinued Rabusertib purchase chest radiographs and bone scan at the 4th year [46] and one study ended chest radiographs at the 3rd year [66]. Table 4 Frequency of different exams from year 1 to 5 of follow-up Variable   1° year 2° year 3° year 4° year 5° year     Min_ Follow-up Int_ Follow-up much Min_ Follow-up Int_ Follow-up Min_ Follow-up Int_ Follow-up Min_ Follow-up Int_ Follow-up Min_ Follow-up Int_ Follow-up times/year times/year times/year times/year times/year times/year times/year times/year times/year times/year History/physical examination 46 RCTs www.selleckchem.com/products/srt2104-gsk2245840.html Median 4.0 4.0 2.0 4.0 2.0 2.0 2.0 2.0 2.0 2.0 Lower-Higher limit 1.0-4.0 1.0-4.0 2.0-4.o 1.0-4.0 1.0-2.0 1.0-4.0 2.0 1.0-4.0 1.0-2.0 1.0-4.0 Physical examination 18 RCTs Median 3.0 3.5 2.5 3.0 2.0 2.5 2.0 2.0 2.0 2.0 Lower-Higher limit 1.0-4.0 3.0-4.0 1.0-4.0 2.0-4.0 2.0-4.0 3.0-4.0 1.0-4.0 1.0-3.0 1.0-4.0 1.0-3.0 Chest radiograph 33 RCTs Median   1.0   1.0   1.0   1.0   1.0 Lower-Higher limit   1.0-3.0   1.0-3.0   1.0-3.0   1.0-2.0   1.0-2.0 Bone scan 19 RCTs Median   1.0   1.0   1.0   1.0   1.0 Lower-Higher limit   1.0-3.0   1.0-3.0   1.0-3.0   1.0-3.0   1.0-2.0 Liver sonography 24 RCTs Median   1.0   1.0   1.0   1.0   1.0 Lower-Higher limit   1.0-3.0   1.0-3.0   1.0-3.0   1.0-2.0   1.0-2.0 Legends: Min_ = minimal; Int_ = intensive.