Table 1.
Early phase research quality checklist.
| Early Phase Research Quality Checklist: EPRQC* | ||||||
|---|---|---|---|---|---|---|
| REFERENCE | ||||||
| Phase | Preclinical | Clinical—Phase I | Clinical—Phase IIa | Clinical—Phase IIb | Clinical—Phase IIb | Reported on page no, comments |
| Dose preparation | Dose ranging | Dose screening | Dose finding (response) | Dose finding (optimal) | ||
| Aim | To investigate the response to systematic variations of individual dose constructs. | To systematically escalate and de-escalate dose to identify minimum to maximum tolerated dose range. | To screen a dose regimen to determine if it is sufficiently promising to test in a phase IIb trial; considering feasibility, safety, and efficacy. | To investigate a potential dose response relationship of a dose regimen (includes single and/or multiple doses). | To identify the optimal dose regimen to test in a Phase III trial. | |
| OBJECTIVE | ||||||
| 1 | Was one of the experiment objectives to investigate the response to individual dose construct? | Was one of the study objectives to find a dose range (minimum to maximum dose)? | Was one of the study objectives to screen a dose/s? | Was one of the study objectives to investigate the response to a dose regimen? | Was one of the study objectives to identify the optimal dose regimen? | |
| 2a | N/A | Was there a prespecified list of “dose limiting criteria”? | N/A | N/A | N/A | |
| 2b | N/A | Was there a limiting value assigned to the “dose limiting criteria”? | N/A | N/A | N/A | |
| 3 | N/A | Did the study differentiate between “dose limiting criteria” and events related to underlying disease, and/or unrelated adverse events? | Did the study differentiate between causality related adverse events and underlying disease progression, and/or unrelated adverse events? | Did the study differentiate between causality related adverse events and underlying disease progression, and/or unrelated adverse events? | Did the study differentiate between causality related adverse events and underlying disease progression, and/or unrelated adverse events? | |
| 4 | Was the chosen measure/s appropriate to test the targeted outcome and was it translatable to the clinical population? | Was a justification for the “dose limiting criteria” provided, and were the measures valid and reliable? | Was a justification for the chosen measure/s provided, and were the measures valid and reliable? | Was a justification for the chosen measure/s provided, and were the measures valid and reliable? | Was a justification for the chosen measure/s provided, and were the measures valid and reliable? | |
| DESIGN: DOSE SPECIFICATION | ||||||
| 5a | N/A | Was the starting dose specified? | Was the dose to be screened specified? | Was the lowest dose within the dose regimen specified? | Was the lowest dose within the dose regimen specified? | |
| 5b | N/A | Was the starting dose justified? | Was dose to be screened justified? | Was the lowest dose within the dose regimen justified? | Was the lowest dose within the dose regimen justified? | |
| 6a | Was the dose regimen clearly outlined? | Did the study state how the dose level will be determined for the second and subsequent cohorts? | N/A | Was the dose regimen clearly outlined? | Was the dose regimen clearly outlined? | |
| 6b | Was the dose regimen justified? | Was a justification provided for how the dose levels were determined? | N/A | Was the dose regimen justified? | Was the dose regimen justified? | |
| 7 | Was the dose allocation method clearly described? | Was the dose allocation method clearly described? | Was the dose assignment method clearly described? | Was the dose allocation method clearly described? | Was the dose allocation method clearly described? | |
| ANALYSIS | ||||||
| 8 | Was the definition of the data analysis set appropriate for the study design? | Was the definition of the data analysis set appropriate for the study design? | Was the definition of the data analysis set appropriate for the study design? | Was the definition of the data analysis set appropriate for the study design? | Was the definition of the data analysis set appropriate for the study design? | |
| 9 | Was the actual dose regimen and responses clearly reported? | Was the actual dose range (minimum to maximum dose) and responses clearly reported? | Was the actual dose/s and response/s clearly reported? | Was the actual dose regimen and responses clearly reported? | Was the actual dose regimen and responses clearly reported? | |
| 10 | Did the dose allocation match the described methods? | Did the dose allocation match the described methods? | Did the dose assignment match the described methods? | Did the dose allocation match the described methods? | Did the dose allocation match the described methods? | |
| 11 | Was a rationale for the statistical method chosen provided? | Was a rationale for the statistical method chosen provided? | Was a rationale for the statistical method chosen provided? | Was a rationale for the statistical method chosen provided? | Was a rationale for the statistical method chosen provided? | |
| 12 | Was the process of estimating the recommended dose regimen clearly explained? | Was the process of estimating the dose range (minimum to maximum dose) to be tested in phase IIa trials clearly explained? | Was the process of estimating the recommended dose to test in phase IIb trials explained? | Was the process of estimating the response to the dose regimen to be tested in later phase IIb clinical trials explained? | Was the process of estimating the optimal dose regimen to be tested in phase III clinical trials explained? | |
| Score | Score | Score | Score | Score | ||
SCORING: N/A or Not relevant = 0. Relevant and stated in the article = 1. Relevant but not stated in the article = −1.
*
This table has been adapted from the Phase I quality assessment checklist (26). For full details of the adaptation process see Supplementary Material 1.