Table 2 Clinical trials articles found after initial inclusion/exclusion criteria applied

Schwartz and Sendor [26]

Main Research Question: Explores the impact of helping others on the physical and psychosocial wellbeing of the provider

Drug/Intervention: Non-directive telephone support to patients with multiple sclerosis

Type of Clinical Trial: Secondary analysis of non-randomized providers of one treatment arm from RCT

RS Hypotheses: Peer support may be a benefit to the helper through changing self-evaluation despite no change in objective function or circumstances

Sample: Lay peer support providers (n = 5) of patients with multiple sclerosis who were trained as part of a clinical trial to evaluate the role of peer support; 132 patients with MS who were randomized either to directive or non-directive group intervention. Telephone group n = 67, coping group n = 60, non-randomized peer supporters who implemented the telephone group n = 5

RS Methods: Effect sizes were estimated for each QoL outcome in each group; Chi-square test of association between small, medium, and large effect sizes

RS Findings: Peer supporters had 3–8 times the benefit on a number of measures (psychosocial role performance, adaptability, well-being) compared to patients receiving an intervention

Bernhard et al. [27]

Main Research Question: To evaluate whether patients with colon cancer undergoing surgery with or without adjuvant chemotherapy change the internal standards on which they base their QL estimation, and, if they do so, whether this reframing alters interpretation of QL findings

Drug/Intervention: Post-operative adjuvant chemotherapy, two arms received different dose as compared to observation only

Type of Clinical Trial: A phase-III trial (the Swiss Group for Clinical Cancer Research [SAKK] 40/93) for colon cancer

RS Hypotheses: Expected that patients’ estimates of their pre-surgery QL would be lower after surgery compared to before. Also, expected that the patients' retrospective estimates of their QL at the beginning of adjuvant therapy would be lower than estimates made beforehand. This reframing was expected to be stronger in patients receiving chemotherapy compared to those without

Sample: 187 patients with early colon cancer (no. per arm not provided)

RS Methods: Then-test method. The first hypothesis (i.e., worse scores of retrospective estimations) was investigated by paired t-tests between the pre- and then-test assessments separately for surgery and the adjuvant phase, the latter separately by treatment and overall. The second hypothesis (i.e., worse scores of retrospective estimations in patients with chemotherapy as compared to those without) was investigated by F-tests of changes between pre- and then-tests

RS Findings: (1) Patients reported their pre-surgery QL after surgery significantly lower than before the surgery, and their pre-adjuvant QL under treatment or observation also lower than at the beginning. (2) In the adjuvant phase, in contradiction to our hypothesis, chemotherapy had almost no impact on these changes attributed to reframing. However, conventionally assessed changes indicated an improvement in QL. (3) After adjustment of current QL scores under treatment or observation to patients' retrospective estimation, the treatment effects were diluted but the overall improvement was substantially amplified in most QL indicators

Bernhard et al. [28]

Main Research Question: To evaluate whether the response shift affects the perception of health for utility evaluation in cancer clinical trials

Drug/Intervention: Post-operative adjuvant chemotherapy, two arms received different dose as compared to observation only

Type of Clinical Trial: A phase-III trial (the Swiss Group for Clinical Cancer Research [SAKK] 40/93) for colon cancer

RS Hypotheses: Expected that patients' estimates of their pre-surgery QL would be lower after surgery compared to before. Also, expected that the patients' retrospective estimates of their QL at the beginning of adjuvant therapy would be lower than estimates made beforehand. This reframing was expected to be stronger in patients receiving chemotherapy compared to those without

Sample: 187 patients with early colon cancer (no. per arm not provided)

RS Methods: Then-test method

RS Findings: Patients estimated pre-surgery health was worse after surgery than before (P = 0.01), and their estimated pre-adjuvant health was worse under treatment or observation than at the beginning (P = 0.001), in agreement with QL indicators. Chemotherapy had no impact on these changes attributed to a response shift. Conventionally assessed changes between the beginning of adjuvant treatment or observation and 2 months later indicated no change in subjective health. Change scores relative to patients’ retrospective estimation revealed an improvement (P = 0.004) in this period

Schwartz et al. [46]

Main Research Question: The primary aim was to evaluate the importance of the facilitated interview portion of the La Crosse intervention in a prospective RCT. A secondary aim was to examine whether the La Crosse intervention affected patients’ preferences by education the patient about the benefits and burdens of end-of-life

Drug/Intervention: Advanced Care Planning intervention. Control group received usually care

Type of Clinical Trial: Single blind RCT

RS Hypotheses: The facilitated interview used in the La Crosse intervention is effective in improving short-term outcomes associated with end-of-life care

Sample: 61 Ambulatory geriatric patients. Respecting choices interview n = 30, nondirective interview n = 30

RS Methods: RS in patients QOL conceptualization were determined using t-test comparing a within-subjects congruence score of the Beliefs and Value Questionnaire. RS of in internal standards were assessed using within-group t-tests on the difference scores of the VAS item s for pain, anxiety, and alertness. The difference in then-test values and baseline values estimated changes in internal standards

RS Findings: The intervention group became less willing to tolerate poor health status, suggesting RS in conceptualization of QOL. There were no changes during follow-up on VAS items for pain, anxiety, or alertness suggesting the participants in both arms did not make response shifts in internal standards. Thus, the patients did not seem to recalibrate their standards of QOL outcomes but rather to reflect on and define their own values after having a better understanding of benefits and burdens of end-of-life care

Bernhard et al. [31]

Main Research Question: To evaluate whether the meaning of QL remains constant over time among patients with early colon cancer

Drug/Intervention: Post-operative adjuvant chemotherapy, two arms received different dose as compared to observation only

Type of Clinical Trial: A phase-III trial (the Swiss Group for Clinical Cancer Research [SAKK] 40/93) for colon cancer

RS Hypotheses: The meaning of QL for patients would be changed across different phases of disease and treatment

Sample: 186 patients with early colon cancer (no. per arm not provided)

RS Methods: Then-test method

RS Findings: Response shift effect was analyzed based on the surgery pre-test and then-test, and the adjuvant pre-test and then-test. There was no evidence to suggest that the parameters for all six QL domains changed

Ahmed et al. [29]

Main Research Question: To assess whether the recovery process following stroke altered individuals’ perceptions of past health status and the impact that change in internal standards (RS) had on ratings over time

Drug/Intervention: Home intervention on stroke outcome

Type of Clinical Trial: 146 stroke patients and 50-control (family caregivers of the patients) study

RS Hypotheses: 1) That individuals with stroke would experience changes in internal standards, not experienced by the control group, 2) given the expected improvements in physical health, individuals with stroke would, on average, retrospectively report worse baseline health status (report lower then test ratings), when rated retrospectively, at 6 weeks and 24 weeks poststroke than what they originally reported it to be at the previous evaluation, 3) that as time goes on and people’s functional ability improves, that individuals would retrospectively reevaluate how they were in the past, 4) those who improved on the objective measures would also have greater improvements in RS adjusted change compared to those who deteriorated or did not change

Sample: 146 stroke patients and 50 controls

RS Methods: The then-test

RS Findings: The pattern of mean scores was indicative of changes in internal standards among individuals with stroke but not for the control group. Memory had an impact on estimates of response shift. Hypotheses related to the objective criterion measures were not supported

Ring et al. [30]

Main Research Question: To determine whether response shift would influence the measurement of treatment efficacy in edentulous patients using individualized quality of life measure (the SEIQOL) through a then-test

Drug/Intervention: Osseo-integrated implant supported dentures vs. conventional dentures within edentulous patients

Type of Clinical Trial: The first phase of a randomized controlled clinical trial designed to assess the impact on QOL of implant supported dentures compared with high quality conventional dentures. Patients wore new high quality conventional dentures for three months before being randomized either to continue with the conventional dentures or to receive implants

RS Hypotheses: High quality dentures or osseo-integrated implants was likely to result in improved eating, communication, appearance, social life, and individual QOL (IQOL). Since the treatment periods were long (three months and six months), the psychological impact of treatment was likely to be marked on the main outcome measure individualized QOL

Sample: 117 edentulous patients (no. per arm not provided)

RS Methods: Then-test method (baseline vs. three months)

RS Findings: Unadjusted SEIQOL index scores revealed no significant impact of treatment at three months (p = 0.33). However, the then-test at 3 months revealed that patients retrospectively rated their baseline IQOL as significantly lower (P < .001) than they had rated it at the time (then-test baseline). Comparison of the 3 month scores with this readjusted baseline indicated a significant treatment effect (then-test baseline, p = 0.016). Also 81% of patients nominated at least one different IQOL domain at 3 months

Ahmed et al. [47]

Main Research Question: To contrast three methodologic approaches for evaluating RS to develop a proposed set of HRQL measurement recommendations under circumstances where RS is expected to occur

Drug/Intervention: Home intervention on stroke outcome

Type of Clinical Trial: 150 stroke patients and 50 -control (family caregivers of the patients) study

RS Hypotheses: None

Sample: 150 stroke patients of whom 92 completed the Patient Generated Index

RS Methods: Structural Equation Modeling, Then-test and an individualized

approach

RS Findings: The Structural Equation Modeling did not show a response shift, contrary to the results of the then test and the individualized approaches

Ahmed et al. [50]

Main Research Question: To assess reconceptualization of HRQL and change of individual values among persons with stroke during the first six months of recovery

Drug/Intervention: Home intervention on stroke outcome

Type of Clinical Trial: Clinical trial Patients—completers (n = 92) and non-completers (n = 58) of Patient Generated Index

RS Hypotheses: None

Sample: 146 stroke patients and 50 controls

RS Methods: Interviews using Patient Generated Index

RS Findings: After reviewing the 46 interviews, 13 (28%) people were classified as having expressed verbalizations reflecting a RS. Many individuals (n = 31) who did not verbalize a response shift had changes in the areas selected between both evaluations

Mayo et al. [34]

Main Research Question: Do different RS detection methods lead to different conclusions about the existence of RS?

Drug/Intervention: 6 weeks of need based nursing interventions delivered by a nurse caregiver following hospital discharge

Type of Clinical Trial: Secondary analysis of stratified, balanced, randomized clinical trial; no blinding

RS Hypotheses: Difference methods of RS detection lead to different conclusions about its presence

Sample: 150/190 persons returning home directly from acute-care hospital following first/recurrent stroke with need for health-care supervision post-discharge due to low function, comorbidity, or isolation; 126 (63 in each group) had the Then-Test

RS Methods: Then-test for RS at the individual level; EFA/CFA of SF-36 and stepwise linear regression for RS at the group level; Analysis of residuals from predictive model of EQ-VAS over time

RS Findings: Residual analysis revealed RS in half the sample. Most of the response shift was positive, people assessed their health better than what would be predicted by their stroke-related disabilities alone; this is a desired feature of the rehabilitation process

Ahmed et al. [35]

Main Research Question: 1) To evaluate whether persons with chronic obstructive pulmonary disease (COPD) experience a response shift after participating in a self-management program. 2) To compare the Oort and Schmitt Structural Equation Modeling approaches

Drug/Intervention: 4 weeks of hospital-based self-management education, after which they were randomized to 8 weeks of either home-based or outpatient hospital-based rehabilitation

Type of Clinical Trial: Unblinded 2-arm trial

RS Hypotheses: None

Sample: 252 patients with COPD: outpatient-based rehabilitation n = 126, home-based rehabilitation n = 126

RS Methods: The Oort and Schmitt Structural Equation Modeling methods

RS Findings: The Oort approach showed significant changes between the no-RS model and models removing invariance constraints for the residual of the CRQ dyspnea (uniform recalibration) and intercepts of the SGRQ activity and impact subscales (nonuniform recalibration). Change in factor means showed changes in the physical health factor, which was slightly lower in unadjusted as compared with the RS adjusted model. The Schmitt procedure was not supportive of any RS effect

Robertson et al. [36]

Main Research Question: To understand what QOL means to people and how this influences the interpretation of HRQOL questionnaires

Drug/Intervention: Intensive bisphosphonate therapy vs symptomatic therapy

Type of Clinical Trial: multicenter RCT

RS Hypotheses: Reference frame choice changes over time

Sample: Paget's Disease: PRISM RCT with n = 1331, of whom 21 were interviewed to assess reference frame

RS Methods: Cognitive interviewing

RS Findings: Health not the most important factor in evaluating QOL. Social relationships were impacted by reduced vitality. Reference frames changed over time and interacted in complex ways, which may create potential bias when supplemental questions are not used to assess standards of comparison

Mayo and Scott [32]

Main Research Question:

Drug/Intervention: 6 weeks of need-based nursing interventions delivered by a nurse caregiver following hospital discharge

Type of Clinical Trial: Stratified, balanced, randomized clinical trial; no blinding

RS Hypotheses: Not a study to detect response shift. Hypothesized that extent of nursing intervention (complexity and QoL domains targeted) leads to increased likelihood of achieving improvement in relevant outcomes (those targeted by the intervention)

Sample: 190 persons returning home directly from acute-care hospital following first/recurrent stroke with need for health-care supervision post-discharge due to low function, comorbidity, or isolation. Nurse case-manager group n = 96, usual care group n = 94

RS Methods: Binary indicator for each of 7 QoL domains (change of 0.5 SD); GEE to estimate odds ratio of improvement; multiple imputation used for missing change scores

RS Findings: NA

Gandhi et al. [37]

Main Research Question: To investigate the influence of explanatory and confounding variables on HRQOL among hypertensive Coronary Artery Disease patients by taking into account the issues of measurement bias and response shift in measurement

Drug/Intervention: Antihypertensive treatment with either a verapamil SR- or atenolol-based strategy to achieve blood pressure control

Type of Clinical Trial: 2 armed trail

RS Hypotheses: The phenomenon of RS in HRQOL might have been caused by clinical variables such as antihypertensive treatment strategies, change in systolic and diastolic pressure; which are considered as catalysts in RS theory

Sample: 788 hypertensive Coronary Artery Disease patients taking anti-hypertensive drugs and have depressive symptoms. Not given how many in each arm

RS Methods: Structural Equation Modeling

RS Findings: Patients reporting worsened Physical Functioning and Role Physical scores can be explained by individuals undergoing the process of recalibration response shift over time, and patients recalibrated their perception of Physical Functioning over a 1 year period, which was attributed to gender

Nirenberg et al. [38]

Main Research Question: Whether the intervention itself may impact on the accuracy of self-report (trust, knowledge re target behavior)

Drug/Intervention: Community Service vs Motivational Interviewing

Type of Clinical Trial: RCT; blinding not mentioned

RS Hypotheses: No

Sample: 478 people court-referred for high-risk driving and/or alcohol or other drug charges, Community service n = 160, Motivational Interviewing n = 318

RS Methods: Compared ratings with rankings and defined levels of agreement

RS Findings: Ratings reflect what matters and rankings reflect what matters most; ratings are stable over time, rankings are more variable

Sajobi et al. [39]

Main Research Question: Is there reprioritization of HRQOL in patients treated surgically and/or medically for temporal lobe epilepsy?

Drug/Intervention: Surgery vs. medical treatment

Type of Clinical Trial: RCT, unblinded

RS Hypotheses: Various domains of HRQOL will demonstrate RS over 1-year in patients with TLE randomized to either surgical or medical treatment

Sample: 80 TLE patients randomized to surgical or medical treatment. Surgical group n = 40, medical group n = 40

RS Methods: Lix, Sajobi, et al. Relative Importance Method for reprioritization

RS Findings: Evidence for reprioritization in social function and seizure domains of QOLEI

Mollerup and Johansen [33]

Main Research Question: To determine whether response shift effects are present in PROs of hand eczema severity

Drug/Intervention: Nursing counseling vs. usual care

Type of Clinical Trial: Secondary analysis of RCT; unblinded

RS Hypotheses: RS is present in patient assessment of eczema severity

Sample: 224/306 patients with hand eczema enrolled in a trial of nursing support. (no. per arm not provided)

RS Methods: Defined presence of RS as the proportion of patients who endorsed lower VAS for worst-ever at 6 months compared to baseline

RS Findings: Referred to "downwardly adjusting their assessment of VAS worst."

Machuca et al. [48]

Main Research Question: To describe response-shift patterns in people with dentine hypersensitivity using Classification and Regression Trees (CART) and to explore the convergent validity of CRT with the then-test and ideals approaches

Drug/Intervention: 8-week clinical trial of mouthwashes for dentine hypersensitivity

Type of Clinical Trial: Secondary analysis of 4-arm RCT; unblinded

RS Hypotheses: No

Sample: 75 general population participants with dentine hypersensitivity

RS Methods: CART, the then-test and ideals analysis were conducted with the screening and week-8 assessments to investigate recalibration

Hoerger et al. [49]

Main Research Question: Does educating patients about evidence from the Early Palliative Care Study would increase preferences for palliative care?

Drug/Intervention: Intervention participants received a web-based summary of the Early Palliative Care Study; controls received no intervention

Type of Clinical Trial: Not stated but after submitting their data, participants were given more information about the study, links to educational and mental health resources, and controls were provided with access to the intervention materials. Thus, it was probably single blind and then unblinded for participants after data were collected

RS Hypotheses: Yes: educating patients would lead them to be more likely to prefer palliative care

Sample: 598 patients with prostate, breast, lung, colon/rectal, skin, and other cancer diagnoses. Intervention n = 309 and control n = 289

RS Methods: ANCOVA model testing for intervention effects (IV) on preferences (DV) after adjusting for demographic and clinical factors (covariates)

Reliable change index focuses on proportion of individuals experiencing change, rather than mean changes at the group level. The RCI accounts for whether observed changes exceed what would be expected given the test–retest reliability of the measure and sampling error

RS Findings: The intervention had a favorable impact on participants’ preferences for emotional, cognitive, and behavioral aspects of palliative care. Preferences for palliative care increased by about 3/4 SD among intervention participants. The intervention effect remained in sensitivity analyses using a more conservative outcome indicator

Murata et al. [40]

Main Research Question: Investigated the quantification of the response shift–adjusted treatment effect on quality-of-life (QOL) data in a randomized controlled trial

Drug/Intervention: Taxane versus S-1

Type of Clinical Trial: open-label, noninferiority, phase 3

RS Hypotheses: Implied that there would be RS effects in RCT data

Sample: 290 metastatic breast cancer patients: Taxane n = 139 and S-1 n = 151

RS Methods: Structural equation modeling techniques in addition to quantifying the “true” treatment effect. Measurement invariances in the values of the common factor loadings, intercepts, and residual variances between before treatment and at the 3-, 6-, and 12-month visits were considered the response shift effects

RS Findings: In the Taxane group, we observed positive recalibration effects for role functioning and positive reprioritization and negative recalibration effects for emotional functioning. In the S-1 group, we observed positive reprioritization and negative recalibration effects for emotional functioning and positive reprioritization effects for social functioning

"Decomposition of the changes between before treatment and the 3-month visit showed that most of the positive changes in emotional functioning were related to reprioritization response shifts in both treatment groups. This result reflected patient relief or calmness from psychological depression after a diagnosis of cancer metastasis or progression and a priority shift from a patient’s own health conditions to other things, for example, usual activities, while the negative impact of diagnosis would be almost temporary. In contrast, the negative changes in physical, role, and cognitive functioning in the Taxane group were related to nonresponse shift effects, including the true change from the treatment. This finding is interpreted as a reflection of the adverse effects of Taxane treatment such as fatigue and sensory neuropathy."

"More accurate decision making requires further improvement in the evaluation reliability of observed HRQOL data during clinical trials through detailed analyses of the response shift effects…Careful consideration regarding the response shift effect in their study design would be required to observe a reliable conclusion without bias."

Sanders et al. [41]

Main Research Question: Whether lack of difference between treatments in Goal-Concordant Care was due to methodological challenges with how GCC measured

Drug/Intervention: Serious Illness Care Program

Type of Clinical Trial: Cluster-RCT; blinding not mentioned

RS Hypotheses: None

Sample: 203 patients with advanced cancer. Unclear how many in each group

RS Methods: Compared ratings with rankings and defined levels of agreement

RS Findings: Ratings reflect what matters and rankings reflect what matters most; ratings are stable over time, rankings are more variable

Schwartz et al. [43]

Main Research Question: To investigate possible response-shift effects in a recent clinical trial testing a new treatment (the drug Eculizumab in preventing relapse) for Neuromyelitis Optica Spectrum Disorder (NMOSD)

Drug/Intervention: Eculizumab vs. placebo

Type of Clinical Trial: A randomized, double-blind trial

RS Hypotheses: Treatment arm and then relapse status were hypothesized ‘catalysts’ of response shift

Sample: 143 patients with NMOSD: Eculizumab n = 95, placebo n = 48

RS Methods: The analysis began by testing an omnibus response-shift hypothesis and then implemented a series of random-effects models to elucidate specific response-shift effects. A series of random-effects models are: 1) testing group differences in patterns of emphasis (characterizing a recalibration response shift), 2) testing group differences over time in patterns of emphasis (characterizing reprioritization response shift), and 3) predicting each QOL domain from catalyst group after adjusting for other QOL domains (characterizing reconceptualization response shift)

RS Findings: In the omnibus test, the standard QOL model captured substantially less well the experience of placebo as compared to Eculizumab group. Treat-related recalibration and reconceptualization response-shift effects were detected. Detected relapse-related response shifts included recalibration, reprioritization, and reconceptualization

Schwartz et al. [11]

Main Research Question: Given treatment and relapse-related response shift effects in VAS among people with NMOSD who participated in a clinical trial comparing Eculizumab to Placebo, this study aimed to “back-translate” the VAS into the MCS/PCS scores that would have been observed if response shift had not been present

Drug/Intervention: Eculizumab vs. placebo

Type of Clinical Trial: A randomized, double-blind trial

RS Hypotheses: Response-shift effects were obfuscating treatment arm differences in mental health

Sample: 143 patients with NMOSD: Eculizumab n = 95, placebo n = 48

RS Methods: The analysis sought to estimate MCS and PCS scores at baseline and at end of study by Treatment Arm, with and without response-shift effects. To translate MCS and PCS scores from the predicted value of VAS with and without response-shift effects, the classical-test theory method of equipercentile ranking was used to quate scores. A serial of random intercept models were implemented:

Model 1 included fixed effects representing recalibration and reprioritization response-shift effects (i.e., group-by-MCS (or PCS) and group-by-MCS (or PCS)-by-time) and estimated the VAS scores with response effects. Model 2 estimated VAS scores without response shift, presumed that VAS ratings were attributable solely to MCS/PCS and treatment, but not to recalibration and reprioritization in the interaction terms (i.e., obtained VAS scores that removed variance related to recalibration and reprioritization response shifts). Model 3: took the estimated VAS without response-shift effects (predicted VAS value from model (2) and then adding the residual from model 1 to account for idiosyncratic variabilities under response shift

RS Findings: Eculizumab patients’ MCS and PCS scores that include response-shift effects have a more truncated range, which generally makes them look better off than scores that remove response-shift effects. In contrast, Placebo patients’ crosswalks for both MCS and PCS exhibit similar ranges and similar linked scores whether including or excluding response-shift effects. Also, Placebo only and were more prominent at extremes of the MCS score distribution

Verdam et al. [45]

Main Research Question: To gain insight into relevance of RS in psychological health intervention research

Drug/Intervention: Various psychological interventions

Type of Clinical Trial: 3 RCTs: (1) internet-delivered CBT for insomnia in general population (n = 52/arm); (2) meaning-centered group psychotherapy for cancer survivors (n = 170 total or 85 per arm); (3) internet-based CBT for diabetes patients with depression (n = 255 total or 130 and 125 per arm)

RS Hypotheses: That response shifts occur in the primary self-reported outcomes, is induced by psychological treatment, will occur only in the intervention groups, and not in the control groups. That the detected response shifts are clinically meaningful and substantially impact the assessment of change. That is, when response shift is taken into account, the treatment effects will be different (reduced or amplified). Moreover, that clinical and background variables are predictive of response shift

Sample: 104 insomniacs; 170 cancer survivors; 255 depressed diabetics

RS Methods: Structural Equation Modeling

RS Findings: RS in both arms but did not affect trial results. RS may provide insight into differential treatment effectiveness

Schwartz et al. et al. [44]

Main Research Question: Do patients treated with ravulizumab or eculizumab for 26 weeks experience adaptation in their assessment of HRQOL compared to the general population?

Drug/Intervention: 26 week treatment with either ravulizumab or eculizumab

Type of Clinical Trial: Secondary analysis of two Phase 3 open-label studies evaluation non-inferiority of Ravulizumab compared to Eculizumab; general population data came from a cross-sectional sample from 11 European countries

RS Hypotheses: Patients whose condition is well managed will evidence RS effects

Sample: Patients with PNH treated with one of two agents participating in one of two phase 3 clinical trials (Trial 301, n = 246; Trial 302, n = 195); General population (n = 15,386)

RS Methods: Multivariate analysis of covariance; Estimation of effect sizes; Logistic regression framework to test for differential item functioning

RS Findings: Recalibration (uniform DIF over time in physical function, role function, emotional function, fatigue, and pain) and Reprioritization (non-uniform DIF over time in emotional, fatigue, and pain); Ravulizumab showed larger effect sizes; no treatment DIF but did uncover group DIF and DIF over time