TABLE 3.

Published trials with manuscripts available on ClinicalTrials.gov – PRO characteristics (n = 18)

Study	PRO result in abstract	PRO instrument	Phase	Frequency of assessment	Statistical methods	How were the PRO outcomes analysed?	MCID described?	Missing PRO data present?	Number of patients with missing PRO data described?	Reasons for missing PRO data described?	Method for managing missing PRO data described?	PRO considered for MTD/RP2D?
Taylor et al. 32 , 33 (NCT00692900)	Yes	MDASI with ovarian cancer specific items	Phase 1 dose escalation	Weekly	Descriptive analysis	Over dose Over time (baseline to each time period)	No	Yes	Yes	Partial	No	Used to confirm the MTD
Wyatt et al. 34 (NCT01585246)	Yes	IPSS, FACT‐Prostate	Phase 1/2	IPSS: baseline, weeks 2–10, 12, 14 and 22. FACT‐P: baseline, week 12, 14 and 22	Descriptive analysis and inferential statistic	Baseline differences between treatment groups [two‐sample t‐test] Over time and between treatment groups [LME]	No	Not described	No	No	Yes	No
Van Zandwijk 35 (NCT02369198)	No	EORTC QLQ C30	Phase 1 dose escalation	Weekly	Descriptive analysis	Over time(from baseline to 8 treatment weeks)	No	Yes	Yes	No	No	No
Haddad et al. 36 (NCT01276496)	No	PRO‐CTCAE	Phase 1 dose escalation	Weekly	Descriptive analysis	Not described	No	Yes	Yes	Yes	No	No
Sampath et al. 37 (NCT01923506)	Yes	IPSS, SHIM, Merrick rectal function scale	Phase 1 dose escalation	Baseline and at each follow‐up appointment for 3 years	Descriptive analysis and Inferential statistic	Over dose and over time, and between patient subgroups [statistical test not stated]	No	Yes	No	No	No	No
Reiss et al. 38 (NCT01264432)	Yes	EORTC QLQ C30	Phase 1 dose escalation	Baseline, every 2 cycles, during follow‐up	Inferential statistic	Over time [paired t‐test]; Over different patient subgroups [two‐sample t‐test]	Yes	Yes	Yes	Yes	Yes	Used to confirm the MTD
Dinkic et al. 39 (NCT01238770)	No	EORTC QLQ C30, EORTC Ovar‐28	Phase 1 dose escalation	Baseline, every 3 cycles, during follow‐up	Unclear	Over time [statistical test not stated]	No	Not described	No	No	No	No
Laetsch et al. 31 (NCT02637687)	No	Peds QL Infant, Peds QL Core module, Wong Baker Pain Faces	Phase 1 dose escalation	Every cycle	Descriptive analysis	Over time (baseline to each time period)	Yes	Yes	Yes	No	No	No
Aguilar et al. 40 (NCT00638612)	Yes	FACT‐hepatobiliary	Phase 1 dose escalation	Baseline, follow up	Descriptive analysis	Over time (baseline to each time period) and over different treatment arms	No	Yes	Yes	No	No	No
Subbiah et al. 41 (NCT02240238)	Yes	EORTC QLQ C30	Phase 1/2	Not stated	Descriptive analysis	Over time (baseline to last assessment)	No	Yes	Yes	No	No	No
Crew et al. 42 (NCT00516243)	No	SF‐36	Phase 1 dose escalation	Baseline, 6 months	Unclear	Over time [statistical test not stated]	No	Not described	No	No	No	No
Watanabe et al. 49 (NCT01763788)	No	LCSS, ASBI	Phase 1/2	Not stated	Descriptive analysis and Inferential analysis	Time to worsening via Kaplan–Meier estimates and over treatment groups [cox regression]	Yes	Not described	No	No	No	No
Kumar et al. 43 (NCT01864018)	No	FACT/GOG neurotoxicity questionnaire	Phase 1/2	Baseline, after each cycle for 4 cycles, then every 3 cycles	Descriptive analysis	Over time (for each cycle)	No	Yes	Yes	No	No	No
Verstovsek et al. 44 (NCT00509899)	No	Myelofibrosis Symptom Assessment Form, EORTC QLQ C30	Phase 1/2	Baseline, 1 and 6 months	Descriptive analysis and Inferential statistic	Over dose, over time and over treatment groups [statistical test not stated]	No	No	No	No	No	No
Boulin et al. 46 (NCT01040559)	No	EORTC QLQ C30	Phase 1 dose escalation	Baseline, D15, D30 and D60 post TACE	Descriptive analysis	Over dose and over time (baseline to 1 month at each dose) [Mean difference and 95% CI stated]	Yes	Yes	Yes	No	No	Used to confirm the MTD
Verstovsek et al. 45 (NCT01423851)	Yes	Myelofibrosis Symptom Assessment Form	Phase 1/2	Baseline, Day 1 of Cycles 2 and 4, Day 1 of every 3 cycles thereafter	Descriptive analysis	Over time (after 4 and 12 weeks of treatment)	No	Yes	No	No	No	No
Siegel et al. 47 (NCT01129570)	No	FACT‐hepatobiliary	Phase 1 dose escalation	Week 1, 6, and 12	Unclear	Only baseline data was reported	No	Not applicable	No	No	No	No
Martin‐Broto et al. 48 (NCT02275286)	No	EORTC QLQ C30	Phase 1/2	Every 3 months for 24 months	Descriptive analysis and Inferential statistic	Over time (baseline to cycle3) [Mann‐Whitney or Kruskal‐Wallis]	No	Not described	No	No	No	No

Abbreviations: ASBI, Average Symptom Burden Index; IPSS, International Prostate Symptom Scale; LCSS, Lung Cancer Symptom Scale; LME, linear mixed effects; MCID, minimal clinically important difference; MDASI, MD Anderson Symptom Inventory; MTD, maximum tolerated dose; RP2D, phase 2 recommended dose; SF‐36, 36‐item Short Form Survey; SHIM, Sexual Health Inventory for Men; TACE, trans‐arterial chemoembolization.