Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy Induced Peripheral Neurotoxicity

OBJECTIVEThere is not agreement on the “gold standard” for detection and grading of Chemotherapy Induced Peripheral Neurotoxicity (CIPN) in clinical trials. We performed an observational prospective study to assess and compare both patient-based and physician-based methods.METHODSConsecutive patients, aged 18 years or older, candidates for neurotoxic chemotherapy were enrolled in US/EU/Australia. A trained investigator performed physician-based scales (Total Neuropathy Score clinical [©Johns Hopkins University; TNSc], then used to calculate TNS nurse [TNSn]) and supervised the patient-completed questionnaire (FACT/GOG-NTX©). Evaluations were performed before and at the end of chemotherapy. On participants without neuropathy at baseline we assessed the association between TNSc, TNSn and FACT/GOG-NTX. Considering a previously established Minimal Clinically Important Difference (MCID) for FACT/GOG-NTX, we identified participants with and without a clinically important deterioration according to this scale. Then, we calculated the MCID for TNSc and TNSn as the difference in the mean change score of these scales between the two groups.RESULTSData from 254 participants were available, 180 (71%) had normal neurological status at baseline. At the end of the study, 88% of participants developed any grade of neuropathy. TNSc, TNSn and FACT/GOG-NTX showed good responsiveness (standardized mean change from baseline to end of chemotherapy >1 for all scales). On the 153 participants without neuropathy at baseline and treated with a known neurotoxic chemotherapy regimen we verified a moderate correlation in both TNSc and TNSn scores with FACT/GOG-NTX (Spearman correlation index r=0.6). On the same sample, considering as clinically important a change in the FACT/GOG-NTX score of at least 3.3 points, the MCID was 3.7 for TNSc and 2.8 for the TNSn.CONCLUSIONSMCID for TNSc and TNSn have been calculated, and the TNSn can be considered a reliable alternative objective clinical assessment if a more extended neurological examination is not possible. Moreover, the FACT/GOG-NTX score can be reduced to 7 items and these items correlate well with the TNSc and TNSn.CLASSIFICATION OF EVIDENCEThis study provides Class III evidence that a patient-completed questionnaire and nurse-assessed scale correlate with a physician-assessed scale.

One‐year clinically important deterioration and long‐term clinical course in Japanese patients with COPD: a multicenter observational cohort study

Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with a complex progression of many clinical presentations, and clinically important deterioration (CID) has been proposed in the Western studies as a composite endpoint of disease progression. The aim of this study was to investigate the relationships between 1-year CID and the following long-term clinical outcomes in Japanese patients with COPD who have been reported to have different characteristics compared to the Westerners. Methods Among Japanese patients with COPD enrolled in the Hokkaido COPD cohort study, 259 patients who did not drop out within the first year were analyzed in this study. Two definitions of CID were used. Definition 1 comprised ≥ 100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥ 4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, or moderate or severe exacerbation. For Definition 2, the thresholds for the FEV1 and SGRQ score components were doubled. The presence of CID was evaluated within the first year from enrollment, and analyzed the association of the presence of CID with following 4-year risk of exacerbations and 9-year mortality. Results Patients with CID using Definition 1, but not any single CID component, during the first year had a significantly worse mortality compared with those without CID. Patients with CID using Definition 2 showed a similar trend on mortality, and had a shorter exacerbation-free survival compared with those without CID. Conclusions Adoption of CID is a beneficial and useful way for the assessment of long-term disease progression and clinical outcomes even in Japanese population with COPD. The definition of CID might be optimized according to the characteristics of COPD population and the observation period for CID.

One-year Clinically Important Deterioration and Long-Term Clinical Course in Japanese patients with COPD: A Multicenter Observational Cohort Study

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with a complex progression of many clinical presentations, and clinically important deterioration (CID) has been proposed in the Western studies as a composite endpoint of disease progression. The aim of this study was to investigate the relationships between 1-year CID and the following long-term clinical outcomes in Japanese patients with COPD who have been reported to have different characteristics compared to the Westerners.Methods: Among Japanese patients with COPD enrolled in the Hokkaido COPD cohort study, 259 patients who did not drop out within the first year were analyzed in this study. Two definitions of CID were used. Definition 1 comprised ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), ≥4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, or moderate or severe exacerbation. For Definition 2, the thresholds for the FEV1 and SGRQ score components were doubled. The presence of CID was evaluated within the first year from enrollment, and analyzed the association of the presence of CID with following 4-year risk of exacerbations and 9-year mortality.Results: Patients with CID using Definition 1, but not any single CID component, during the first year had a significantly worse mortality compared with those without CID. Patients with CID using Definition 2 showed a similar trend on mortality, and had a shorter exacerbation-free survival compared with those without CID.Conclusions: Adoption of CID is a beneficial and useful way for the assessment of long-term disease progression and clinical outcomes even in Japanese population with COPD. The definition of CID might be optimized according to the characteristics of COPD population and the observation period for CID.

Prognostic value of clinically important deterioration in COPD: IMPACT trial analysis

IntroductionClinically important deterioration (CID) is a multicomponent measure for assessing disease worsening in chronic obstructive pulmonary disease (COPD). This analysis investigated the prognostic value of a CID event on future clinical outcomes, and effect of single-inhaler triple versus dual therapy on reducing CID risk in patients in the IMPACT trial.MethodsIMPACT was a Phase III, double-blind, 52-week multicenter trial. Patients with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomised 2:2:1 to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg. CID at the timepoint of interest was defined as: a moderate/severe exacerbation, or ≥100 mL decrease in trough forced expiratory volume in 1 s or deterioration in health status (≥4.0 unit increase in St George's Respiratory Questionnaire total score or ≥2.0 unit increase in COPD Assessment Test score) from baseline. A treatment-independent post hoc prognostic analysis compared clinical outcomes up to Week 52 in patients with/without a CID by Week 28. A prospective analysis evaluated time-to-first CID with each treatment.ResultsPatients with a CID by Week 28 had significantly increased exacerbation rates after Week 28, smaller improvements in lung function and health status at Week 52 (all p<0.001), and increased risk of all-cause mortality after Week 28 versus patients who were CID-free. FF/UMEC/VI significantly reduced CID risk versus dual therapies (all p<0.001).ConclusionsPrevention of short-term disease worsening was associated with better long-term clinical outcomes. FF/UMEC/VI reduced CID risk versus dual therapies; this effect may improve long-term prognosis in this population.FundingGSK (CTT116855/NCT02164513).