IntroductionBackground

Patient-reported outcome (PRO) instruments are defined as any report regarding a patient’s health status obtained directly from the patient, excluding interpretation of the patient’s responses by clinicians or other individuals []. PRO data consist of information obtained directly from patients concerning their health status, symptoms, treatment adherence, physical and social functioning, health-related quality of life, and satisfaction with health care [-]. Serving as noninvasive, comprehensive, and patient-centered metrics, PROs play a pivotal role in enhancing patient engagement, facilitating informed clinical decisions, and improving patient-clinician communication [-]. High-quality PRO measures examined in rigorous trials can evaluate treatment effectiveness, assess patient adherence to treatment, guide drug research, and inform health care policies [,]. In addition, some PRO instruments could supplement safety data and contribute to the assessment of tolerability (eg, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE]) [,].

In particular, PROs are valuable end points in trials of disabling, chronic, and incurable conditions because they systematically capture the patients’ perspectives in a scientifically rigorous way [,,]. Recognizing their importance, clinical trials focused on tumors are increasingly incorporating PRO instruments as primary or secondary outcomes [-]. The European Commission has indicated the priority of preventing cancer and ensuring a high quality of life for patients with cancer within the framework of Europe’s Beating Cancer Plan []. The incorporation of PROs in clinical trials offers distinct advantages, including improvements in health-related quality of life, patient-clinician communication, and economic benefits from reduced health care use [-]. To uphold best practices in tumor clinical trials that use PROs, several methodological recommendations have emerged in recent years, such as SPIRIT-PRO (Standard Protocol Items: Recommendations for Interventional Trials–Patient-Reported Outcome), CONSORT-PRO (Consolidated Standards of Reporting Trials–Patient-Reported Outcome), SISAQOL (Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints), and other relevant guidelines [-,]. However, PRO measures often receive lower priority in the design of oncology-related clinical trials when compared to survival, imaging, and biomarker-related outcomes [].

Objectives

In China, PROs are increasingly being used in clinical trials, but there are challenges as well. A cross-sectional survey of interventional clinical trials conducted in China revealed that only 29.7% of the included trials listed PRO instruments as primary or secondary outcomes []. Moreover, there is a notable absence of comprehensive assessments evaluating the application of PRO instruments in tumor clinical trials in China. Unlike previous cross-sectional studies that encompassed all types of clinical trials, our study primarily examined adult tumor clinical trials in China that have listed PRO instruments as primary or secondary outcomes, referencing the methodologies and reporting patterns of a previous study []. We extracted the registration information of adult randomized clinical trials conducted in China to systematically analyze the application of PRO instruments in tumor clinical trials, aiming to evaluate the application of PRO instruments in adult tumor clinical trials in China and provide potential directions for further investigation.

MethodsStudy Design

This cross-sectional study was designed to describe the characteristics of adult tumor clinical trials conducted in China between January 1, 2010, and June 30, 2022, that listed PRO instruments as primary or secondary outcomes. All clinical trials should be registered, and data of clinical trials were collected from 2 clinical trial registries, namely ClinicalTrials.gov and the Chinese Clinical Trial Registry, with public disclosure. We conducted data retrieval and export in July 2022. The clinical trials covered 34 provincial-level administrative regions in accordance with the 2019 version of China’s administrative divisions. We further sought to describe the PRO instruments frequently used in trials encompassing diverse target tumor conditions.

Data Collection Strategy

This study focused on interventional randomized clinical trials conducted in China involving participants aged ≥18 years (). Duplicate trials with 2 registration identification numbers were treated as a single trial (ClinicalTrials.gov records were retained). The evaluation of tumor clinical trials included three types of information: (1) basic information (registration number, registration date, scientific name, recruiting country, and other information), (2) key information (outcome, target disease, and age and sex of participants), and (3) characteristic information (main sponsor’s location, study settings, number of setting centers, study stage, funding source, and intervention type).

‎Figure 1. Trial exclusion and classification criteria. PRO: patient-reported outcome. Data Classification

PRO instruments were defined by the US Food and Drug Administration in 2009 [] as any report about a patient’s health status obtained directly from the patient, excluding interpretation of the patient’s response by clinicians or other individuals. Trials using PRO instruments as primary or secondary outcomes were considered PRO trials. On the basis of a previous study of PRO labeling of new US Food and Drug Administration–approved drugs (2016-2020) [], eligible trials were classified into four groups: (1) trials that listed PRO instruments as primary outcomes, (2) trials that listed PRO instruments as secondary outcomes, (3) trials that listed PRO instruments as coprimary outcomes, and (4) trials without any mention of PRO instruments.

Statistical Analysis

Data related to the characteristics of the included trials (clinical phase, study setting, participant age and sex, region of the primary sponsor, setting center, number of PROs, funding source, and type of intervention) were extracted independently by 2 authors with a predesigned data extraction table. Owing to the varied categories and wide variation of target diseases, we classified similar target diseases based on classifications from the American Joint Committee on Cancer Staging Manual, 8th Edition (). On the basis of this categorization of diseases, we consolidated the PRO instruments used in each trial to identify those used most frequently. We conducted quantitative analysis only on items that listed the names of PRO instruments for a more detailed understanding of the commonly used evaluation tools. All data analyses were performed using Stata (version 14.0; StataCorp LLC).

Ethical Considerations

According to the Common Rule (45 CFR part 46) of the US Department of Health and Human Services (Office for Human Research Protections), this study is exempt from institutional review board approval and the requirement for informed patient consent because it did not involve clinical data or human participants. This study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guidelines designed for observational studies in epidemiology.

ResultsTrial Characteristics

presents a comprehensive overview of the included trials. The study included 7251 tumor-focused randomized controlled trials conducted in China between January 1, 2010, and June 30, 2022. Of these 7251 trials, 3276 (45.18%) were sourced from ClinicalTrials.gov, and 3975 (54.82%) were identified from the Chinese Clinical Trial Registry. Of these 7251 trials, after excluding 806 (11.12%) trials (n=5, 0.6% duplicates; n=465, 57.7% non-Chinese trials; n=321, 39.8% trials involving children; and n=15, 1.9% trials with incomplete reports), 6445 (88.88%) eligible trials were identified for analysis.

Table 1. Characteristics of all identified trials and patient-reported outcome (PRO)–related trials.CharacteristicsTrials (n=6445), n (%)PRO trials (n=2390), n (%)Phase
Early phasea1317 (20.43)575 (24.06)
2873 (13.55)218 (9.12)
31004 (15.58)284 (11.88)
4779 (12.09)269 (11.26)
Otherb1514 (23.49)537 (22.47)
Unclear958 (14.86)507 (21.21)Setting
Hospital6034 (93.62)2256 (94.39)
Community3 (0.05)3 (0.13)
Otherc300 (4.65)96 (4.02)
Unclear108 (1.68)35 (1.46)Age (y)
≥186098 (94.62)2252 (94.23)
>65100 (1.55)42 (1.76)
Unclear247 (3.83)96 (4.02)Sex
Male only267 (4.14)107 (4.48)
Female only1000 (15.52)410 (17.15)
Male and female5170 (80.22)1869 (78.2)
Unclear8 (0.12)4 (0.17)Regions of China
Southwest517 (8.02)207 (8.66)
Northeast185 (2.87)83 (3.47)
North797 (12.37)321 (13.43)
Northwest173 (2.68)63 (2.64)
East3745 (58.11)1309 (54.77)
South682 (10.58)286 (11.97)
Central340 (5.28)120 (5.02)
Otherd6 (0.09)1 (0.04)Centers involved
Single5626 (87.29)2046 (85.61)
Multiple716 (11.11)312 (13.05)
Unclear103 (1.6)32 (1.34)PRO instruments used
1-3N/Ae2144 (89.71)
4-6N/A218 (9.12)
7-9N/A25 (1.05)
≥10N/A3 (0.13)Funding source
Industry752 (11.67)186 (7.78)
Nonindustry institutions5443 (84.45)2120 (88.7)
Combinationf219 (3.4)71 (2.97)
Unclear31 (0.48) 13 (0.54)

aThe early phase trials included a clinical pretest as well as phase 0 and phase 1 trials.

bDiagnostic new technique clinical study, inspection technology, and trials involving multiple phases.

cRehabilitation center, nursing home, campus, centers for disease control, home, and research institute.

dThe trials were conducted in China, but their sponsor was based overseas.

eN/A: not applicable.

fCombination trials were funded partly by industry and partly by nonindustry institutions, such as universities, hospitals, and so on.

Of the 2,155,306 participants recruited in all included trials, 139,297 (6.46%) were involved in trials with PRO instruments as primary outcomes, 400,064 (18.56%) in trials with PRO instruments as secondary outcomes, and 74,287 (3.45%) in trials with PRO instruments as coprimary outcomes. Among the 6445 trials included, 2390 (37.08%) used PRO instruments as either primary or secondary outcomes, while 4055 (62.92%) did not use any PRO instrument.

The majority of the studies (6098/6445, 94.62%) did not impose any age restrictions on participants (children were excluded). In trials involving PROs, the proportion of older participants (aged >65 y; 42/2390, 1.78%) was slightly higher than in those without PROs (100/6445, 1.55%). Among all trials that incorporated PRO measurements, 17.15% (410/2390) included only female participants, while 4.48% (107/2390) included only male participants. Furthermore, in trials involving only female participants, the vast majority (974/1000, 97.4%) studied breast and female reproductive organ tumors. In trials exclusively involving male participants, more than half (135/267, 50.5%) centered around male genital organ tumors.

Regarding trial phases, of the 6445 clinical trials, early phase trials were the most prevalent (n=1317, 20.43%), followed by phase 3 trials (n=1004, 15.58%), phase 2 trials (n=873, 13.56%), and phase 4 trials (n=779, 12.09%). Of the 2390 PRO-related trials, early phase trials were again the most common (n=575, 24.06%), followed by phase 3 trials (n=284, 11.88%), phase 4 trials (n=269, 11.26%), and phase 2 trials (n=218, 9.12%).

Most of the trials (6034/6445, 93.62%) were conducted in hospitals, with hardly any (3/6445, 0.05%) conducted in community settings. More than half of the primary sponsors were located in eastern China (3745/6445, 58.11%), followed by northern (797/6445, 12.37%) and southern (682/6445, 10.58%) China, while 18.85% (1215/6445) of the primary sponsors were situated in other regions of China, such as the southwestern, central, northwestern, and northeastern regions. Similar patterns were observed for studies involving PROs. The majority of the major sponsors (1916/2390, 80.17%) originated from the eastern, northern, and southern regions of China, while 19.79% (473/2390) hailed from the southwestern, central, northeastern, and northwestern regions. There were differences in the proportions of PRO trials were noted among different provinces; the distribution of PRO instruments across Chinese provinces can be found in .

Moreover, 87.29% (5626/6445) of the trials were single-center trials, and only 11.11% (716/6445) were multicenter trials. Similar phenomena were observed for PRO-related studies, but multicenter trials accounted for a slightly higher percentage (312/2390, 13.05%). Of the 2390 PRO trials, 2144 (89.71%) used 1 to 3 PRO instruments, followed by 4 to 6 (n=218, 9.12%) and 7 to 9 (n=25, 1.05%) PRO instruments. The majority of the trials were nonindustry-funded trials (5443/6445, 84.45%), while 11.67% (752/6445) were industry-funded trials.

shows the frequency of intervention types used across different trial classifications. The data indicated that more than a third of the included trials used drugs as the intervention (2496/6445, 38.73%), followed by combination therapies (1350/6445, 20.95%) and surgery (1044/6445, 16.2%). Among clinical trials involving drug interventions, nearly four-tenths (989/2496, 39.62%) used PRO instruments as their outcomes. Trials using drugs as the intervention exhibited a higher incidence of using PRO instruments as their primary or coprimary outcomes (468/989, 47.32%) compared to trials using other intervention types.

Table 2. Frequency of intervention types used across different trial classifications.InterventionTrials (n=6445), n (%)PROa trials

Trials, n/N (%)Primary outcome, n/N (%)Secondary outcome, n/N (%)Coprimary outcome, n/N (%)Drug2496 (38.73)989/2496 (39.62)250/989 (25.28)521/989 (52.68)218/989 (22.04)Biological400 (6.21)73/400 (18.25)8/73 (10.96)61/73 (83.56)4/73 (5.48)Surgery1044 (16.2)329/1044 (31.51)124/329 (37.69)184/329 (55.93)21/329 (6.38)Radiation187 (2.9)57/187 (30.48)11/57 (19.3)44/57 (77.19)2/57 (3.51)Combination1350 (20.95)375/1350 (27.78)52/375 (13.87)297/375 (79.2)26/375 (6.93)Otherb968 (15.02)567/968 (58.57)196/567 (34.57)153/567 (26.98) 218/567 (38.45)

aPRO: patient-reported outcome.

bOther interventions included acupuncture, physical exercise, and psychosocial treatment.

Conditions and Participants

The annual counts of tumor clinical trials are listed in . During the study period—from January 1, 2010, to June 30, 2022—the number of tumor clinical trial registrations exhibited a consistent upward trajectory, paralleled by a commensurate increase in the number of clinical trials related to PROs.

‎Figure 2. Number of tumor clinical trials analyzed. PRO: patient-reported outcome.

and depict the distribution of trial counts and corresponding participant numbers across different tumor types, respectively, wherein PROs served as outcomes. Among the 2390 tumor-related trials that used PRO instruments as primary or secondary outcomes, the top 5 tumors were thorax (448/2390, 18.74%), upper gastrointestinal tract (306/2390, 12.8%), lower gastrointestinal tract (300/2390, 12.55%), breast (289/2390, 12.09%), and head and neck (177/2390, 7.41%) tumors. Trials regarding female reproductive organ (168/2390, 7.03%) and hepatobiliary system (146/2390, 6.11%) tumors were also frequently observed. Male genital organ tumors (56/2390, 2.34%), central nervous system tumors (51/2390, 2.13%), endocrine system tumors (47/2390, 1.97%), and urinary tract tumors (33/2390, 1.38%) all accounted for proportions ranging from 1% to 5%, and hematologic malignant tumors (22/2390, 0.92%), neuroendocrine tumors (14/2390, 0.59%), bone tumors (8/2390, 0.33%), skin tumors (4/2390, 0.17%), ophthalmic tumors (2/2390, 0.08%), and soft tissue sarcoma (1/2390, 0.04%) constituted <1% of the trials.

‎Figure 3. Number of trials with patient-reported outcomes (PROs). ‎Figure 4. Number of participants with patient-reported outcomes (PROs).

Among the 613,648 participants enrolled in these PRO trials, 134,940 (22%) were diagnosed with lower gastrointestinal tract tumors, 131,470 (21.42%) with upper gastrointestinal tract tumors, and 79,068 (12.88%) with thorax tumors. Furthermore, there were a number of patients with breast tumors (63,238/613,648, 10.31%), female reproductive organ tumors (440,975/613,648, 6.68%), head and neck tumors (35,642/613,648, 5.81%), or hepatobiliary system tumors (22,044/613,648, 3.59%), each involving >10,000 patients. By contrast, conditions with <10,000 participants encompassed central nervous system tumors (8897/613,648, 1.45%), endocrine system tumors (8472/613,648, 1.38%), male genital organ tumors (8357/613,648, 1.36%), urinary tract tumors (6784/613,648, 1.11%), neuroendocrine tumors (3539/613,648, 0.58%), hematologic malignant tumors (2629/613,648, 0.43%), bone tumors (825/613,648, 0.13%), skin tumors (311/613,648, 0.05%), ophthalmic tumors (274/613,648, 0.04%), and soft tissue sarcoma (266/613,648, 0.04%).

PRO Instruments Used in Clinical Trials

presents the number of explicitly specified PROs where trials precisely listed the names of the PRO instruments and the number of implicitly specified PROs where trials referenced patients’ subjective feelings without specifying the instruments used, separately for the 3 trial types. Specifically, the trial that specified the PRO instruments used was classified into “explicitly specified PROs,” and the trial that did not specify the instruments used was classified into “implicitly specified PROs.” It was evident that in primary and coprimary outcome trial sets, a greater number of trials explicitly listed the PRO instruments compared to those that did not specify the instruments used. Among the 3 trial types, the coprimary outcome category exhibited the highest proportion of explicitly specified PROs (339/489, 69.3%).

Table 3. Number of explicitly specified patient-reported outcomes (PROs) and implicitly specified PROs used in different trial classifications (n=2390).ClassificationExplicitly specified PROs, n (%)Implicitly specified PROs, n (%)Primary outcome (n=641)335 (52.3)306 (47.7)Secondary outcome (n=1260)606 (48.1)654 (51.9)Coprimary outcome (n=489)339 (69.3)150 (30.7)

- display the frequency of use of PRO scales for different diseases under the 3 categories. In trials using PRO instruments as coprimary outcomes, the visual analog scale (VAS) and the numeric rating scale (NRS) were the most commonly used scales for various tumors. For trials using PRO instruments as primary outcomes, the VAS was the most commonly used scale for various diseases. For trials using PRO instruments as secondary outcomes, the most commonly used scale for each disease was the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30 (EORTC QLQ-C30).

Table 4. Frequency of patient-reported outcome (PRO) instruments used as primary outcomes in different classifications of tumor trials by condition.ConditionTrials (n=1280), n (%)Instrument frequency in trials with PRO instruments as primary outcomes

Trials, n/N (%)Instrument, n/N (%)Instrument, n/N (%)Instrument, n/N (%)Thorax tumors217 (16.95)56/217 (25.81)VASa, 25/56 (44.64)NRSb, 9/56 (16.07)EORTC QLQ-LC43c, 4/56 (7.14)Breast tumors176 (13.75)41/176 (23.3)VAS, 14/41 (34.15)SF-36d, 4/41 (9.76)PSQIe, 3/41 (7.32)Lower gastrointestinal tract tumors173 (13.52)43/173 (24.86)VAS, 14/43 (32.56)IPSSf, 4/43 (9.3)LARSg, 4/43 (9.3)Upper gastrointestinal tract tumors140 (10.94)46/140 (32.86)VAS, 13/46 (28.26)EORTC QLQ-C30h, 12/46 (26.09)EORTC QLQ-STO22i, 8/46 (17.39)Head and neck tumors101 (7.89)21/101 (20.79)VAS, 3/21 (14.29)UW-QOLj, 3/21 (14.29)NRS, 2/21 (9.52)Female reproductive organ tumors85 (6.64)20/85 (23.53)VAS, 6/20 (30)NRS, 3/20 (15)EORTC QLQ-C30, 3/20 (15)Hepatobiliary system tumors67 (5.23)14/67 (20.9)VAS, 6/14 (42.86)EORTC QLQ-C30, 3/14 (21.43)QoR-40k, 1/14 (7.14)Male genital organ tumors31 (2.42)11/31 (35.48)VAS, 7/11 (63.64)NRS, 3/11 (27.27)EORTC QLQ-C30, 2/11 (18.18)Endocrine system tumors30 (2.34)16/30 (53.33)VAS, 9/16 (56.25)IDSl, 2/16 (12.5)EORTC QLQ-C30, 1/16 (6.25)Central nervous system tumors25 (1.95)5/25 (20)VAS, 2/5 (40)QoR-40, 1/5 (20)NRS, 1/5 (20)Urinary tract tumors17 (1.33)4/17 (23.53)VAS, 1/4 (25)IIEF-15m, 1/4 (25)QoR-15n, 1/4 (25)Bone tumors8 (0.63)5/8 (62.5)NRS, 2/5 (40)VAS, 2/5 (40)SF-36, 1/5 (20)Hematologic malignant tumors9 (0.7)2/9 (22.22)NRS, 1/2 (50)TCMSSo, 1/2 (50)N/ApNeuroendocrine tumors10 (0.78)N/AN/AN/AN/ASkin tumors3 (0.23)N/AN/AN/AN/AOphthalmic tumors1 (0.08)N/AN/AN/AN/ASoft tissue sarcoma0 (0)N/AN/AN/AN/AOther tumors187 (14.61)51/187 (27.27)VAS, 18/51 (35.29)NRS, 11/51 (21.57)EORTC QLQ-C30, 4/51 (7.84)

aVAS: visual analog scale.

bNRS: numeric rating scale.

cEORTC QLQ-LC43: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Lung Cancer 43.

dSF-36: 36-item Short Form Health Survey.

ePSQI: Pittsburgh Sleep Quality Index.

fIPSS: International Prostate Symptom Score.

gLARS: Low Anterior Resection Syndrome.

hEORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30.

iEORTC QLQ-STO22: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Stomach 22.

jUW-QOL: University of Washington Quality of Life Questionnaire.

kQoR-40: Quality of Recovery-40.

lIDS: Involvement-Detachment Scale.

mIIEF-15: International Index of Erectile Function-15.

nQoR-15: Quality of Recovery-15.

oTCMSS: Traditional Chinese Medicine Symptom Scale.

pN/A: not applicable.

Table 5. Frequency of patient-reported outcome (PRO) instruments used as secondary outcomes in different classifications of tumor trials by condition.ConditionsTrials (n=1280), n (%)Instrument frequency in trials with PRO instruments as secondary outcomes

Trials, n/N (%)Instrument, n/N (%)Instrument, n/N (%)Instrument, n/N (%)Thorax tumors217 (16.95)98/217 (45.16)EORTC QLQ-C30a, 33/98 (33.67)FACT-Lb, 18/98 (18.37)EORTC QLQ-LC13c, 15/98 (15.31)Breast tumors176 (13.75)67/176 (38.07)EORTC QLQ-C30, 23/67 (34.33)FACT-Bd, 16/67 (23.88)EORTC QLQ-BR23e, 13/67 (19.4)Lower gastrointestinal tract tumors173 (13.52)94/173 (54.34)EORTC QLQ-C30, 38/94 (40.43)VASf, 21/94 (22.34)Wexner Scale, 11/94 (11.7)Upper gastrointestinal tract tumors140 (10.94)72/140 (51.43)EORTC QLQ-C30, 41/72 (56.94)EORTC QLQ-OES18g, 15/72 (20.83)VAS, 13/72 (18.06)Head and neck tumors101 (7.89)68/101 (67.33)EORTC QLQ-C30, 38/68 (55.88)EORTC QLQ-H&N35h, 34/68 (50)NRSi, 6/68 (8.82)Female reproductive organ tumors85 (6.64)49/85 (57.65)EORTC QLQ-C30, 18/49 (36.73)VAS, 5/49 (10.2)EORTC QLQ-CX24j, 5/49 (10.2)Hepatobiliary system tumors67 (5.23)37/67 (55.22)EORTC QLQ-C30, 18/37 (48.65)EORTC QLQ-HCC18k, 7/37 (18.92)VAS, 5/37 (13.51)Male genital organ tumors31 (2.42)10/31 (32.26)FACT-Pl, 4/10 (40)BPI-SFm, 3/10 (30)FACT-Gn, 3/10 (30)Endocrine system tumors30 (2.34)7/30 (23.33)VAS, 3/7 (42.86)QoR-40o, 1/7 (14.29)SF-36p, 1/7 (14.29)Central nervous system tumors25 (1.95)14/25 (56)VAS, 8/14 (57.14)NRS, 4/14 (28.57)QoR-15q, 3/14 (21.43)Urinary tract tumors17 (1.33)11/17 (64.71)EORTC QLQ-C30, 3/11 (27.27)VAS, 3/11 (27.27)WHOQOL-BREFr, 2/11 (18.18)Neuroendocrine tumors10 (0.78)10/10 (100)EORTC QLQ-C30, 6/10 (60)EORTC QLQ-PAN26s, 2/10 (20)VAS, 2/10 (20)Hematologic malignant tumors9 (0.7)4/9 (44.44)EORTC QLQ-C30, 2/4 (50)FACITt, 2/4 (50)EQ-5D-5L, 1/4 (25)Skin tumors3 (0.23)3/3 (100)EORTC QLQ-C30, 1/3 (33.33)VAS, 1/3 (33.33)HF-QoLu, 1/3 (33.33)Bone tumors8 (0.63)3/8 (37.5)EORTC QLQ-C30, 2/3 (66.67)BPI-SF, 1/3 (33.33)N/AvOphthalmic tumors1 (0.08)1/1 (100)EORTC QLQ-C30, 1/1 (100)EORTC QLQ-OPT30w, 1/1 (100)N/ASoft tissue sarcoma0 (0)N/AN/AN/AN/AOther tumors187 (14.61)58/187 (31.02)VAS, 12/58 (20.69)EORTC QLQ-C30, 12/58 (20.69) NRS, 9/58 (15.52)

aEORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30.

bFACT-L: Functional Assessment of Cancer Therapy–Lung.

cEORTC QLQ-LC13: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Lung Cancer 13.

dFACT-B: Functional Assessment of Cancer Therapy–Breast.

eEORTC QLQ-BR23: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Breast Cancer 23.

fVAS: visual analog scale.

gEORTC QLQ-OES18: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Oesophageal Cancer 18.

hEORTC QLQ-H&N35: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Head and Neck Cancer 35.

iNRS: numeric rating scale.

jEORTC QLQ-CX24: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Cervical Cancer 24.

kEORTC QLQ-HCC18: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Hepatocellular Carcinoma 18.

lFACT-P: Functional Assessment of Cancer Therapy–Prostate.

mBPI-SF: Brief Pain Inventory–Short Form.

nFACT-G: Functional Assessment of Cancer Therapy–General.

oQoR-40: Quality of Recovery-40.

pSF-36: 36-item Short Form Health Survey.

qQoR-15: Quality of Recovery-15.

rWHOQOL-BREF: World Health Organization Quality of Life Brief Version.

sEORTC QLQ-PAN26: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Pancreatic Cancer 26.

tFACIT: Functional Assessment of Chronic Illness Therapy.

uHF-QOL: Hand-Foot Skin Reaction and Quality of Life.

vN/A: not applicable.

wEORTC QLQ-OPT30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Ophthalmic Cancer 30.

Table 6. Frequency of patient-reported outcome (PRO) instruments used as coprimary outcomes in different classifications of tumor trials by condition.ConditionsTrials (n=1280), n (%)Instrument frequency in trials with PRO instruments as coprimary outcomes

Trials, n/N (%)Instrument, n/N (%)Instrument, n/N (%)Instrument, n/N (%)Thorax tumors217 (16.95)63/217 (29.03)VASa, 22/63 (34.92)NRSb, 17/63 (26.98)EORTC QLQ-C30c, 16/63 (25.4)Breast tumors176 (13.75)68/176 (38.64)VAS, 22/68 (32.35)NRS, 13/68 (19.12)QoR-15d, 9/68 (13.24)Lower gastrointestinal tract tumors173 (13.52)36/173 (20.81)VAS, 13/36 (36.11)EORTC QLQ-C30, 7/36 (19.44)QoR-15, 6/36 (16.67)Upper gastrointestinal tract tumors140 (10.94)22/140 (15.71)VAS, 7/22 (31.82)NRS, 7/22 (31.82)EORTC QLQ-C30, 3/22 (13.64)Head and neck tumors101 (7.89)12/101 (11.88)NRS, 4/12 (33.33)EORTC QLQ-C30, 3/12 (25)TNSSe, 2/12 (16.67)Female reproductive organ tumors85 (6.64)16/85 (18.82)VAS, 6/16 (37.5)BCSf, 2/16 (12.5)NRS, 2/16 (12.5)Hepatobiliary system tumors67 (5.23)16/67 (23.88)NRS, 7/16 (43.75)EORTC QLQ-C30, 2/16 (12.5)PSQIg, 2/16 (12.5)Male genital organ tumors31 (2.42)10/31 (32.26)VAS, 3/10 (30)ICIQ-SFh, 3/10 (30)FACT-Pi, 2/10 (20)Endocrine system tumors30 (2.34)7/30 (23.33)QoR-15, 3/7 (42.86)VAS, 3/7 (42.86)HADSj, 1/7 (14.29)Central nervous system tumors25 (1.95)6/25 (24)VAS, 5/6 (83.33)EORTC IADL-BN32k, 1/6 (16.67)N/AlUrinary tract tumors17 (1.33)2/17 (11.76)NRS, 1/2 (50)QoR-15, 1/2 (50)VAS, 1/2 (50)Hematologic malignant tumors9 (0.7)3/9 (33.33)SASm, 1/3 (33.33)SDSn, 1/3 (33.33)NRS, 1/3 (33.33)Bone tumors8 (0.63)N/AN/AN/AN/ANeuroendocrine tumors10 (0.78)N/AN/AN/AN/ASkin tumors3 (0.23)N/AN/AN/AN/AOphthalmic tumors1 (0.08)N/AN/AN/AN/ASoft tissue sarcoma0 (0)N/AN/AN/AN/AOther tumors187 (14.61)78/187 (41.71)NRS, 24/78 (30.77)VAS, 14/78 (17.95)PSQI, 12/78 (15.38)

aVAS: visual analog scale.

bNRS: numeric rating scale.

cEORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30.

dQoR-15: Quality of Recovery-15.

eTNSS: Total Nasal Symptom Score.

fBCS: Bruggemann Comfort Scale.

gPSQI: Pittsburgh Sleep Quality Index.

hICIQ-SF: International Consultation on Incontinence Questionnaire–Short Form.

iFACT-P: Functional Assessment of Cancer Therapy–Prostate.

jHADS: Hospital Anxiety and Depression Scale.

kEORTC IADL-BN32: European Organisation for Research and Treatment of Cancer Instrumental Activities of Daily Living in Patients With Brain Tumors-32.

lN/A: not applicable.

mSAS: Self-Rating Anxiety Scale.

nSDS: Self-Rating Depression Scale.

To analyze the overall application of scales in explicitly specified PROs by condition, we examined the specific PRO instruments used in trials that explicitly mentioned the PRO instruments as primary or secondary outcomes (). Of the 1280 trials, 321 (25.08%) used the EORTC QLQ-C30 (), which was the most commonly used PRO scale. Of note, the EORTC QLQ-C30 was the most commonly used scale in trials concerning lower gastrointestinal tract, upper gastrointestinal tract, head and neck, female reproductive organ, hepatobiliary system, bone, neuroendocrine, skin, and ophthalmic tumors as well as hematologic malignancies. In addition, the VAS was used in 24.77% (317/1280) of the trials (), predominating in trials involving thorax, breast, male genital organ, endocrine system, central nervous system, and urinary tract tumors. The NRS was also frequently used (169/1280, 13.2%) in cancer trials. More targeted scales have been used for different tumor diseases; for example, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)–Head and Neck Cancer 35 (36/101, 35.6%) was more common in head and neck tumor trials, the EORTC QLQ–Oesophageal Cancer 18 (15/140, 10.7%) and the EORTC QLQ–Stomach 22 (14/140, 10%) were frequently observed in upper gastrointestinal cancer trials, the EORTC QLQ–Colorectal Cancer 29 (14/173, 8.1%) scale was prevalent in lower gastrointestinal cancer trials, the EORTC QLQ–Hepatocellular Carcinoma 18 (8/67, 12%) was frequently found in hepatobiliary system tumor trials, the Functional Assessment of Cancer Therapy (FACT)–Lung (21/217, 9.7%) and the EORTC QLQ–Lung Cancer 13 (19/217, 8.8%) commonly featured in thorax tumor trials, the FACT–Breast (29/176, 16.5%) and the EORTC QLQ–Breast Cancer 23 (16/176, 9.1%) were frequently seen in breast cancer trials, the EORTC QLQ–Ovarian Cancer 28 (6/85, 7%) was a typical scale used in female reproductive organ tumor trials, the FACT–Prostate (7/31, 23%) was often used in male genital organ tumor trials, and the FACT–Anemia (1/9, 11%) and the FACT–Lymphoma (1/9, 11%) were common choices in hematologic malignant tumor trials.

Table 7. Frequency of use of patient-reported outcome (PRO) instruments by condition.ConditionsTrials (n=1280), n (%)Instrument, n/N (%)Instrument, n/N (%)Instrument, n/N (%)Instrument, n/N (%)Instrument, n/N (%)Thorax tumors217 (16.95)VASa, 57/217 (26.27)EORTC QLQ-C30b, 53/217 (24.42)NRSc, 32/217 (14.75)FACT-Ld, 21/217 (9.68)EORTC QLQ-LC13e, 19/217 (8.76)Breast tumors176 (13.75)VAS, 43/176 (24.43)FACT-Bf, 29/176 (16.48)EORTC QLQ-C30, 26/176 (14.77)EORTC QLQ-BR23g, 16/176 (9.09)NRS, 15/176 (8.52)Lower gastrointestinal tract tumors173 (13.52)EORTC QLQ-C30, 49/173 (28.32)VAS, 48/173 (27.75)NRS, 15/173 (8.67)EORTC QLQ-CR29h, 14/173 (8.09)Wexner Scale, 14/173 (8.09)Upper gastrointestinal tract tumors140 (10.94)EORTC QLQ-C30, 56/140 (40)VAS, 33/140 (23.57)NRS, 17/140 (12.14)EORTC QLQ-OES18i, 15/140 (10.71)EORTC QLQ-STO22j, 14/140 (10)Head and neck tumors101 (7.89)EORTC QLQ-C30, 41/101 (40.59)EORTC QLQ-H&N35k, 36/101 (35.64)NRS, 12/101 (11.88)VAS, 11/101 (10.89)PG-SGAl, 8/101 (7.92)Female reproductive organ tumors85 (6.64)EORTC QLQ-C30, 21/85 (24.71)VAS, 17/85 (20)NRS, 6/85 (7.06)SDSm, 6/85 (7.06)EORTC QLQ-OV28n, 6/85 (7.06)Hepatobiliary system tumors67 (5.23)