***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: When a r and omized trial ( NMSG 4/90 ) comparing treatment with melphalan/prednisone to melphalan/prednisone + interferon α‐2b in newly diagnosed multiple myeloma was inititated in 1990 , a quality ‐of‐life assessment was integrated into the study . We used the question naire ( QLQ‐C30 ) developed by the European Organization of Research and Treatment of Cancer ( EORTC ) Study Group on Quality of Life . The QLQ‐C30 incorporates five functional scales , three symptom scales , a global health and quality ‐of‐life scale and some single symptom measures . The question naire was completed prior to treatment and after 1 , 6 , 12 , 24 , 36 and 48 months . 524 ( 90.2 % ) of 581 patients enrolled in the NMSG 4/90 completed the first question naire , and 484 ( 83.3 % ) completed all question naires given to them . All but one of the scales met the minimum criteria of reliability ( Cronbach ’s alpha ≥0.70 ) . Validity was shown by ( 1 ) the ability of the scales to discriminate clearly between patients differing in clinical status as defined by pre‐treatment W.H.O. performance index and Durie & Salmon stage , and ( 2 ) the sensitivity to changes in objective disease status ( response and relapse ) . This is the first report of the measurement of health‐related quality of life in a prospect i ve clinical trial in multiple myeloma . The results demonstrate that the QLQ‐C30 is a reliable and valid instrument for the measurement of quality of life in these patients . The data will be used for a cost – utility analysis of the results of the NMSG 4/90 trial Few studies have evaluated long-term health-related quality of life ( HRQL ) in patients during auto-SCT .  This prospect i ve study examined HRQL in 96 eligible patients before , during and up to 3 years after auto-SCT .  The aim of the study was to make a comprehensive assessment of the frequency and severity of different symptoms in patients undergoing auto-SCT .  The European Organization for Treatment and Research of Cancer Quality of Life Question naire ( EORTC QLQ C-30 ) was administered 13 times . The second week during treatment was the period when patients had the lowest HRQL regarding both total quality of life and function and symptom scales . The patients recovered quickly and just two months after transplantation the baseline values were restored . Three years after transplantation most of the items in the question naire had stabilized , except role function and dyspnea , which had improved . There were significant differences between multiple myeloma ( MM ) and lymphoma patients ’ physical function , quality of life , fatigue and pain during week 2 . At the 3-year follow-up , lymphoma patients indicated a better HRQL than MM patients . The quick recovery of patients after transplantation suggests that treatment is well tolerated ; however , the supportive care could be improved at week 2 , especially for the lymphoma patients In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring  dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials BACKGROUND Health-related quality of life ( HRQoL ) is an important element for consideration in treatment decisions in patients with relapsed/refractory multiple myeloma ( RRMM ) . The pivotal MM-003 ( A Phase 3 , Multicenter , R and omized , Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone vs. High-Dose Dexamethasone in Patients With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study [ NIMBUS ] ) r and omized , open-label , multicenter , phase III trial demonstrated improved progression-free survival ( PFS ) and prolonged overall survival ( OS ) with pomalidomide ( POM ) plus low-dose dexamethasone ( POM + LoDEX ) versus high-dose dexamethasone ( HiDEX ) in patients with RRMM in whom lenalidomide ( LEN ) and bortezomib ( BORT ) had failed . MM-003 also investigated HRQoL as a predefined secondary end point . PATIENTS AND METHODS Recruited patients ( n = 455 ) were refractory to their last treatment and had failed LEN and BORT after ≥ 2 consecutive cycles of each ( alone or in combination ) . Eight clinical ly relevant and vali date d HRQoL domains from the European Organisation for Research and Treatment of Cancer ( EORTC ) QLQ-C30 , EORTC QLQ-MY20 , and EQ-5D question naires were selected for analysis . Time to symptom worsening based on minimally important differences ( MIDs ) was calculated . RESULTS Clinical ly meaningful improvements in HRQoL as determined by MIDs , regression analyses , and best response analyses were observed more frequently in patients receiving POM + LoDEX than in those receiving HiDEX . POM + LoDEX significantly extended median time to clinical ly meaningful worsening in HRQoL versus HiDEX in 4 HRQoL domains and demonstrated a trend in an additional 3 domains . Patients in the HiDEX arm experienced earlier HRQoL deterioration compared with those in the POM + LoDEX arm in each domain analyzed . CONCLUSION POM + LoDEX offer good clinical outcomes that lead to improved and prolonged HRQoL  compared with HiDEX in patients with RRMM and end-stage disease Aims Missing health-related quality of life ( HRQOL ) data in clinical trials can impact conclusions but the effect has not been thoroughly studied in HIV clinical trials . Despite repeated recommendations to avoid complete case ( CC ) analysis and last observation carried forward ( LOCF ) , these approaches are commonly used to h and le missing data . The goal of this investigation is to describe the use of different analytic methods under assumptions of missing completely at r and om ( MCAR ) , missing at r and om ( MAR ) , and missing not at r and om ( MNAR ) using HIV as an empirical example . Methods Medical Outcomes Study HIV ( MOS-HIV ) Health Survey data were combined from two large open-label multinational HIV clinical trials comparing treatments A and B over 48 weeks . Inclusion in the HRQOL analysis required completion of the MOS-HIV at baseline and at least one follow-up visit ( weeks 8 , 16 , 24 , 40 , 48 ) . Primary outcomes for the analysis were change from week 0 to 48 in mental health summary ( MHS ) , physical health summary ( PHS ) , pain and health distress scores analyzed using CC , LOCF , generalized estimating equations ( GEE ) , direct likelihood and sensitivity analyses using joint mixed-effects model , and Markov chain Monte Carlo ( MCMC ) multiple imputation . Time and treatment were included in all models . Baseline and longitudinal variables ( adverse event and reason for discontinuation ) were only used in the imputation model . Results A total of 511 patients r and omized to treatment A and 473 to treatment B completed the MOS-HIV at baseline and at least one follow-up visit . At week 48 , 71 % of patients on treatment A and 31 % on treatment B completed the MOS-HIV survey . Examining changes within each treatment group , CC and MCMC generally produced the largest or most positive changes . The joint model was most conservative ; direct likelihood and GEE produced intermediate results ; LOCF showed no consistent trend . There was greater spread for within-group changes than between-group differences ( within MHS scores for treatment A : −0.1 to 1.6 , treatment B : 0.4 to 2.0 ; between groups : −0.7 to 0.4 ; within PHS scores for treatment A : −1.5 to 0.4 , treatment B : −1.7 to −0.2 ; between groups : 0.1 to 1.1 ) . The size of within-group changes and between-group differences was of similar magnitude for the pain and health distress scores . In all cases , the range of estimates was small < 0.2 SD ( less than 2 points for the summary scores and 5 points for the subscale scores ) . Conclusions Use of the recommended likelihood-based models that do not require assumptions of MCAR was very feasible . Sensitivity analyses using auxiliary information can help to investigate the potential effect that missing data have on results but require planning to ensure that relevant data are prospect ively collected Thalidomide with melphalan/prednisone ( MPT ) was defined as st and ard treatment in elderly patients with multiple myeloma ( MM ) based on five r and omized trials . In one of these trials , HOVON49 , a prospect i ve health-related quality -of-life ( HRQoL ) study was initiated in order to assess the impact of thalidomide on QoL. Patients aged > 65 years with newly diagnosed MM were r and omized to receive melphalan plus prednisone ( MP ) or MPT , followed by thalidomide maintenance in the MPT arm . Two hundred eighty-four patients were included in this side study ( MP , n = 149 ; MPT n = 135 ) . HRQoL was assessed with the EORTC Core QoL Question naire ( QLQ-C30 ) and the myeloma-specific module ( QLQ-MY24 ) at baseline and at predetermined intervals during treatment . The QLQ-C30 subscales physical function ( P = 0.044 ) and constipation ( P < 0.001 ) showed an improvement during induction in favour of the MP arm . During thalidomide maintenance , the scores for the QLQ-MY24 paraesthesia became significantly higher in the MPT arm ( P<0.001 ) . The QLQ-C30 subscales pain ( P = 0.12 ) , insomnia ( P = 0.068 ) , appetite loss ( P = 0.074 ) and the QLQ-MY24 item sick ( P = 0.086 ) scored marginally better during thalidomide maintenance . The overall QoL-scale QLQ-C30-HRQoL showed a significant time trend towards more favourable mean values during protocol treatment without differences between MP and MPT . For the QLQ-C30 subscales emotional function and future perspectives , difference in favour of the MPT arm from the start of treatment was observed ( P = 0.018 and P = 0.045 , respectively ) with no significant ‘ time × arm ’ interaction , indicating a persistent better patient perspective with MPT treatment . This study shows that the higher frequency of toxicity associated with MPT does not translate into a negative effect on HRQoL and that MPT holds a better patient perspective The phase 3 VISTA study ( Clinical Trials.gov NCT00111319 ) in transplant‐ineligible myeloma patients demonstrated superior efficacy with bortezomib‐melphalan‐prednisone ( VMP ; nine 6‐wk cycles ) vs. melphalan‐prednisone ( MP ) but also increased toxicity . Health‐related quality of life ( HRQoL ; exploratory endpoint ) was evaluated using the European Organization for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire ( QLQ‐C30 ) This descriptive , cross‐sectional analysis evaluated the impact of baseline characteristics on health‐related quality of life ( HR‐QoL ) at different stages of multiple myeloma ( MM ) . The bortezomib clinical ‐trial programme evaluated HR‐QoL early and consistently , producing a large multi‐ study data set . Baseline data , captured using the European Organization for Research and Treatment of Cancer ( EORTC ) quality ‐of‐life question naire ( QLQ‐C30 ) , were pooled from six bortezomib r and omized trials conducted in different disease‐stage categories : ‘ New ’ ( previously untreated ; n = 753 ) , ‘ Early ’ ( 1–3 prior therapies ; n = 1569 ) and ‘ Late ’ ( ≥4 prior therapies ; n = 239 ) disease . Mean EORTC global health scores were similar across the three stages . Unexpectedly , emotional , physical and role functioning were higher in the later stages , indicating better perceived health . Symptom scores , including pain , were largely similar or lower in the later versus earlier stages , signifying a lower symptom burden/better symptom control with more advanced disease . Notable variation in HR‐QoL was observed by age and clinical parameters within and across stages . Multivariate modelling indicated that opioid use and performance status were key factors driving overall HR‐QoL across stages . Using an age‐restricted analysis , transplant eligibility had little impact on HR‐QoL in New disease patients . Thus , changes in HR‐QoL over the treatment course of MM are complex and impacted by baseline factors . A prospect i ve observational international inception cohort study that captures key clinical , HR‐QoL and demographic characteristics , along with safety and supportive care information , is needed BACKGROUND This prospect i ve population -based study describes health-related quality of life ( HRQOL ) and disease-specific complaints of patients with multiple myeloma ( MM ) up to 10 yr post- 
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RESULTS Large and medium HRQoL improvements were reported during first-line treatments .
No clinical ly beneficial change or deteriorations in scores of global QoL or fatigue were reported during relapse treatment .
Guidelines for interpreting changes in HRQoL including definitions of MID have been developed ; however , consensus is missing .
Improvements in HRQoL are far more likely to occur during first-line compared to relapsed treatment regimens .