Flowchart of the literature search and screening results.

<p>Flowchart of the literature search and screening results.</p

Primary study endpoints.

<p>The numbers of primary endpoints are presented as reported in the publications.</p><p>a. One publication did not define any endpoint as the primary one, and six named more than one primary endpoint. Therefore, the number of endpoints differs from the number of included studies.</p><p>b. Included median overall survival (time) and survival rates.</p><p>c. Included combined surrogate measures such as PFS.</p><p>d. Included best overall response, clinical response, objective response rate, and (tumor) response rate.</p><p>e. Included early disease progression rate, time to second progression, time to tumor progression, time to treatment failure, and tumor control rate after 6 months.</p><p>f. Included proportion of patients with histologically confirmed malignant glioma on central neuropathological review without residual contrast-enhancing tumor on postoperative MRI, time to CNS metastases (time from randomization to the radiological occurrence of CNS failure), and impact of the addition of GM-CSF to the MPS160/ISA-51 vaccine (maximum change in the frequency of peptide-specific cytotoxic T lymphocytes in peripheral blood from pre-treatment levels (tetramer analysis).</p><p>AA: anaplastic astrocytoma, CNS: central nervous system, DFS: disease-free survival, GM-CSF: granulocyte macrophage colony-stimulating factor, MRI: magnetic resonance imaging, PFS: progression-free survival, PROs: patient reported outcomes.</p><p>Primary study endpoints.</p

Inclusion criteria.

<p>a. IFs added as supplementary information after completion of the project. They refer to the years 2013–2014 (except for the Journal of the American Medical Association: 2015). The numbers are rounded to one decimal place.</p><p>b. We searched the Cochrane Library for Cochrane reviews and health technology assessment reports on four types of advanced solid cancer: glioblastoma (including anaplastic astrocytoma), lung cancer (stage IIIb-IV), malignant melanoma (stage IV), and pancreatic cancer (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136640#pone.0136640.s002" target="_blank">S2 Appendix</a> for list of reviews). To identify the most relevant specialist journals, we screened the lists of the studies included in the 19 reviews and extracted all publications of studies on these four cancer types (n = 157) as well as the names of the journals they were published in. We then assessed journal frequency: If a specific journal was included three or more times in the list of relevant study publications, then it was included in the journal pool.</p><p>c. Selected additionally for glioblastoma, as the search yielded an insufficient number of hits.</p><p>IC: inclusion criterion, IF: impact factor, RCT: randomized controlled trial.</p><p>Inclusion criteria.</p

Examples of unambiguous and ambiguous descriptions of the terminal stage of disease.

<p>Examples of unambiguous and ambiguous descriptions of the terminal stage of disease.</p

Therapeutic goals mentioned in the studies.

<p>a. TG was defined as “the therapeutic benefit that the intervention studied was intended to have for the patients”.</p><p>b. Examples: “to assess the use of porphyrin fluorescence in malignant glioma after administration of 5-aminolevulinic acid for improving resection as defined by postoperative MRI, and to analyse the effect of resection on progression free survival, neurological morbidity, and type and frequency of treatment after progression” [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136640#pone.0136640.ref025" target="_blank">25</a>]; “Besides determining tumor response rate to LM/TMZ [lomeguatrib/temozolomide], we aimed to test whether the combination could produce tumor shrinkage in patients progressing on TMZ alone” [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136640#pone.0136640.ref023" target="_blank">23</a>].</p><p>c. Examples: “to assess efficacy and tumor delivery of cilengitide in patients with recurrent GBM” [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136640#pone.0136640.ref022" target="_blank">22</a>]; “to define the activity of metronomic chemotherapy with either oral etoposide or temozolomide, combined with bevacizumab” [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136640#pone.0136640.ref024" target="_blank">24</a>].</p><p>AA: anaplastic astrocytoma, GBM: glioblastoma, HRQoL: health-related quality of life, MRI: magnetic resonance imaging, TG: therapeutic goal.</p><p>Therapeutic goals mentioned in the studies.</p

Additional file 1: of Health technology assessment of public health interventions: an analysis of characteristics and comparison of methods—study protocol

PRISMA-P+checklist. (DOCX 39 kb

Additional file 3: of The development of CHAMP: a checklist for the appraisal of moderators and predictors

Contains a table with the comparison of our checklist with those of Sun et al. and Pincus et al. (PDF 630 kb