A total of 18 categories were identified (Table 1). The last new category was added from the 14th paper, applying the set of criteria of three consecutive rounds of five papers with no additional category, the paper selection was interrupted with 30 papers (Figure 1). The maximum number of added categories by a single paper was six.
From Figure 1 it can be noticed that all of the 30 papers mentioned the inclusion criteria, seven papers mentioned only inclusion criteria, 13 papers mentioned categories exclusively in inclusion or exclusion criteria, and 10 papers mentioned at least one category (range 1-3 categories) both as inclusion and exclusion criteria.
From Table 2 it can be noticed that out of the 18 categories five were exclusively mentioned in inclusion criteria, three only as exclusion criteria and the remaining 10 categories were used both as inclusion or exclusion criteria. No category was present in all the papers (however the investigated condition was implicit in other parts of the paper when not directly mentioned). The most frequent categories for inclusion criteria were: “Investigated condition” and “Standardized performance status” present in 27 and 26 papers respectively. The next most frequent categories mentioned as inclusion criteria were “Disease staging or characteristic” , “Physiologic functions” and “Age”, including the papers which mentioned them in both criteria. For exclusion criteria the most frequent categories were, “Described comorbidities” , “Treatment” and “Medical History”, including the papers which mentioned them in both criteria as well. The categories used only for exclusion criteria were the least frequent, present in 1 to 3 papers only.
Five categories (“Described comorbidities”; “Disease staging or characteristic”; “Physiologic functions”; “Pregnancy/breastfeeding”; “Treatment”) appeared in at least two papers (ranging from 2-6) both in inclusion and exclusion criteria.
Analyzing the papers in which the same category was used both as the inclusion and exclusion criteria we identified circumstances in which it was justifiable and others in which it could be avoidable. Justifiable were those situations in which some characteristics of the category would be needed and others would compromise the evaluation of the intervention, for example, if the treatment was for early stages of cervical cancer, exposure to some previous treatment (e.g. tumor removal surgery) would be necessary to evaluate the efficacy of some adjuvant therapy to prevent relapse (inclusion) while exposure to chemotherapy could confound the results of the intervention tested (exclusion). Avoidable were those situations in which there is a redundancy of the criteria, for example, negative beta HCG test (inclusion) and pregnancy (exclusion), or negative description of different characteristic, for example, absence of infectious disease (inclusion) and presence of autoimmune disease (exclusion).
As can be observed from Figure 2, in 15 occasions the same criteria was mentioned both in exclusion and exclusion criteria in the same paper, in most of the cases it was considered Justifiable (10 occurrences, 66 % of the cases).
The same analysis was performed for the categories mentioned as inclusion criteria in some papers and as exclusion criteria in others (but never as both in the same paper). In this analysis “Age” and “Adherence to protocol” were majorly described as inclusion criteria and in only one exception for each, described as exclusion, both cases were considered avoidable. The same situation happened for the category “incompatibility/compatibility with de procedure”, although it was majorly an exclusion criteria instead of inclusion (“being able to tolerate the surgery”). For the remaining category “Response to previous treatment” three papers described it as inclusion criteria focusing on disease persistence and two papers as exclusion criteria one mentioning adverse effects and the other inefficacy of specific treatment to restore some physiological levels, both cases considered justifiable.
In the second phase of the study we investigated if the categories which were exclusively listed under inclusion and exclusion criteria could be found in the opposite criteria in at least one clinical trial. After the search the only criteria which continued exclusively as inclusion criteria were “Gender”, and “Investigated condition” and as exclusion criteria “Conflict of interests/Ethical”. It is worth mentioning that the Investigated condition varied across the studies and gender as well. The criteria “Generic nonspecific exclusion” was too unspecific to be searched.