Table 3. Reported PRO rationale (items 2a and P2b) and authors’ interpretation of PRO in relation to clinical findings (items P20/21 and 22) in primary reports of trials with separate primary and supplemental papers.
Extracted text was abridged where appropriate, as indicated by a series of periods (…), but otherwise presented verbatim.
| Author [citation] | PRO rationale | Level of detail* | Interpretation of PRO in relation to clinical findings: | Level of detail† | |
|---|---|---|---|---|---|
| Ajani [6] [7] | 1° | “To investigate whether adding [intervention] to [control] could improve patient outcomes (time-to-progression [TTP], overall survival [OS}, quality of life. . .” “Time to 5% definitive deterioration in global health status assed by QLQ-C30 was the primary quality of life parameter. “ | Detailed | “. . . [Intervention] resulted in significantly improved TTP (primary end point), OS, and overall response rate (secondary end points), with global health status (quality of life). . . preserved for a longer time.” | Detailed |
| 2° | “. . .to investigate whether the better efficacy with [intervention] was counterbalanced by. . .the impact. . .on patient QOL” “The primary endpoint of the QOL assessment was. . .global health status” | Detailed | “.. significantly better preservation of QOL for patients treated with [intervention].. as a result of a significantly higher level of efficacy. . . . despite a higher incidence of some toxicities. . .” | General | |
| Au[4] [8] | 1° | “. . .no trials have demonstrated an effect of [intervention] on. . . .quality of life. . .” “The secondary end points were. . .quality of life, assessed by mean changes in scores of physical function and global health status..” | Detailed | “[Intervention] improves overall survival and progression-free survival and preserves quality of life measures. . .” | General |
| 2° | “…. we hypothesized a priori that [intervention] would result in a decrease in the magnitude and rate of decline in HRQL, particularly in physical function and overall well-being.” | Detailed | “Patients who received [intervention] experienced significantly less HRQL deterioration and a longer time before clinically significant deterioration occurred. These results are important, because…although [intervention]. . . results in improved OS, PFS, RR, and DCR…the magnitude of these benefits. . .was not large.” “. . .[intervention] offers clinically important survival and HRQL benefits. . .” | General | |
| de Boer [9] [10] | 1° | No PRO rationale | Absent | No integration of PRO and clinical data | Absent |
| 2° | “. . .to compare the quality of life of patients. . .who underwent [intervention] with patients.. who underwent [control]” | General | “..comparing. . .quality of life..is of great interest because a choice between the..two treatment options proves to be difficult..based on overall survival. However…no lasting differences in the quality of life of patients. . .were found.” | General | |
| Braga[11] [12] | 1° | “To clarify the value of [intervention]. . .quality of life. . .should be considered” | General | “[intervention] resulted in earlier postoperative recovery, better cosmesis and improved quality of life. . .compared to [control].” | General |
| 2° | “The primary endpoint was to compare the impact of [intervention] and [control] on 30-day postoperative morbidity.” “Recovery of social and physical activity was evaluated. . .by a specificd adaptation of the SF-36. . .” | Detailed | “. . .the [intervention] resulted in a reduction of both the overall morbidity rate and the length of hospital stay, and in a faster recovery of physical and social activity.” | Detailed | |
| Chau [13] [14] | 1° | No PRO rationale | Absent | No integration of PRO and clinical data | Absent |
| 2° | “. . .to assess QOL. . . .in patients receiving [intervention]” | General | “[Intervention] was associated with significantly better quality of life. . . Due to the shorter treatment duration, [intervention] had a faster time of QOL recovery. Quality adjusted survival was also in favour of the [intervention]… | General | |
| Hallböök [15] [16] | 1° | No PRO rationale | Absent | No integration of PRO and clinical data | Absent |
| 2° | “We hypothesized that such clear differences in clinical bowel function [with the intervention] would also be reflected in the score of a general quality of life instrument……” | Detailed | “The observed difference in clinical bowel function was not. . . reflected in an improved QOL score. . .” | General | |
| Janson [17] [18] | 1° | No PRO rationale | Absent | No integration of PRO and clinical data | Absent |
| 2° | “. . .with the hypothesis that [intervention] results in an improved HRQL when compared with [control]” | Detailed | “HRQL was better..after [intervention]. At present, several studies indicate that the oncologic results are at least equal after [intervention].” | General | |
| Kabbinavar [19] [20] | 1° | No PRO rationale | Absent | No integration of PRO and clinical data | Absent |
| 2° | “The primary HRQoL endpoint was the time to deterioration in HRQoL measured by the Colorectal Cancer Subscale score” | Detailed | “this prospective HRQoL analysis supports the clinical benefit of [intervention] in improving time to disease progression and prolonging overall survival, without compromising patients’ HRQoL”. | General | |
| King [5] [21] | 1° | “The aim of this study was to compare. . . quality of life. . .in a prospective group of patients undergoing [intervention]” | General | “Patients undergoing [intervention] stay in hospital half as long. . .with no. . .deterioration in quality of life. . .” “. . .clinical improvements resulting from [intervention] did not cause significant deterioration in quality of life. . .” | General |
| 2° | “. . .to compare recovery after [intervention] and [control]. . .using. . .self-report and observer data.” | General | “The earlier discharge in the [intervention] group did not result in any deterioration in quality of life outcomes compared with those in the [control] group” “Despite perioperative optimization of [control], short-term outcomes were better following [intervention]. There was no deterioration in quality of life or increased cost associated with the [intervention].” | General | |
| Kopec [22] [23] | 1° | “A secondary aim was to compare quality of life. . .” | General | No integration of PRO and clinical data | Absent |
| 2° | “We hypothesized that the [intervention] would be associated with higher HRQL and that it would be perceived as more convenient.” …. “The primary end point for this study was the FACT-C total score.” | Detailed | “The efficacy of the two regimens is similar, as demonstrated.. by the survival and disease-free survival analyses. . . This underscores the importance of patient-reported outcomes..” “Both regimens … do not differ in their impact on HRQL.” | General | |
| Marijnen [24] [25] | 1° | No PRO rationale | Absent | No integration of PRO and clinical data | Absent |
| 2° | “. . .we studies the effects of [intervention] on the HRQL and sexual functioning. . .” | Detailed | “The results of this study enable physicians and patients to weigh the beneficial effect of [intervention] on local recurrence against the price to be paid in terms of HRQL and sexual functioning.” | Detailed | |
| Siena [26] [27] | 1° | No PRO rationale | Absent | No integration of PRO and clinical data | Absent |
| 2° | “. . .exploratory analyses were conducted that assessed the association between [trial outcome variables] and HRQoL” | General | “. . . lack of disease progression was associated with … higher HRQoL for [intervention] patients only. . .Lack of disease progression was associated with better symptom control, HRQoL, and OS. | General | |
| Stephens [28] [29] | 1° | No PRO rationale | Absent | No integration of PRO and clinical data | Absent |
| 2° | “. . .the advantages of [intervention] to all patients needs to be balanced against any negative impact on patients’ quality of life”. “. . .the primary quality-of-life aims as “What is the longer-term (2-year) effect of the treatments on (1) sexual function and (2) bowel function?” Secondary outcome measures were “What is the effect of treatment on physical function and general health?” To address these questions, the sexual dysfunction and bowel function scales from the QLQ-CR38 and the physical function and general health scales from the MOS SF-36 were used.” | Detailed | “Therefore our results, together with those of the Dutch trial, provide convincing data on the impact of surgery and PRE on sexual and bowel function.” “The information presented in this article should allow clinicians to discuss with patients an estimate of the benefit of PRE in terms of reduction in LR risk balanced against the detrimental toxicity that is attributable to PRE.” | Detailed | |
| Weeks [30] [31] | 1° | No PRO rationale | Absent | “The detailed quality of life component of this trial suggests that greater benefits in terms of the quality of life and recovery may be possible if fewer procedures are converted.” | General |
| 2° | “The trial was also designed to test the hypothesis that [intervention] is associated with superior QOL outcomes” “the study protocol specified. . .the variability in pain distress item and the global ratings scale” | Detailed | “[Intervention].. results in statistically significant but clinically modest decreases in the duration of postoperative in-hospital analgesia and in length of stay. . . However, these differences do not translate into statistically significant improvements in symptoms or QOL. . .” | General | |
| Wu[32] [33] | 1° | No PRO rationale | Absent | No integration of PRO and clinical data | Absent |
| 2° | “We hypothesised that patients receiving [the intervention] would have more symptoms and greater fatigue than patients receiving [the control], with treatment arms difference most prominent at the 6-month assessment, and probably continuing up to 1 year after random assignment.” | Detailed | “Although the morbidity rate was higher in [intervention] patients than in [control] patients, our analysis indicates that [intervention] did not adversely influence QOL” | General |
* Detailed rationale/hypothesis: specifying a PRO domain or hypothesized effect; general rationale/hypothesis: any other description; absent: no rationale. See methods for more details
† Interpretation was considered “detailed” where authors discussed the direction of change (e.g. increased/decreased/no change) of a specific PRO domain (e.g. physical function) in relation to the direction of change of a specific clinical outcome (e.g. survival). All other discussions, where present, were considered “partial” interpretations. Where no appropriate text was identified, interpretation was considered “absent”. See methods for more details