Supportive care and chemotherapy (CT) versus supportive care alone in advanced non-small cell lung cancer (NSCLC): A meta-analysis using individual patient data (IPD) from randomised clinical trials (RCTs)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7582-7582 ◽  
Author(s):  
S. Burdett ◽  
L. A. Stewart ◽  
J. F. Tierney ◽  
C. Le Pechoux
Keyword(s):  
Supportive Care ◽  
Meta Analysis ◽  
Alkylating Agents ◽  
Performance Status ◽  
Single Agent ◽  
Rank Test ◽  
Absolute Benefit ◽  
Absolute Effect ◽  
The Absolute ◽  
Treatment Comparisons

7582 Background: Building on a previous IPD meta-analysis of CT (BMJ 1995;311:899–909) which suggested that CT may have a role in the treatment of NSCLC, we have carried out a new, up-to-date IPD meta-analysis. This includes RCTs, regimens and outcomes that were not available in 1995. This new meta-analysis examines the role of CT in 7 treatment comparisons. Here we report the effectiveness of supportive care plus CT compared with supportive care alone. Methods: We conducted a systematic search for RCTs followed by the central collection, checking and re-analysis of updated IPD. Results from individual RCTs were combined using the stratified (by trial) log rank test to calculate individual and pooled hazard ratios (HRs). Previously included RCTs using long-term alkylating agents were excluded from this analysis due to their antiquity. Results: IPD were obtained on 2,666 patients from 15 RCTs. 11 RCTs used cisplatin-based CT regimens, 4 RCTs used single agent CT (etoposide, navelbine, gemcitabine, paclitaxel). This added 6 RCTs and 1,702 patients to the 1995 analyses. The results show a highly significant benefit of CT on survival (HR=0.78 95% Confidence Interval 0.71–0.84, p<0.000001), with an absolute benefit of 8% (from 20% to 28%) at 12 months across all patients. There was no evidence of a difference in effect (p=0.69) between trials that used cisplatin-based regimens (11 RCTs, HR=0.76), etoposide alone (1 RCT, HR=0.87) or newer single agents (3 RCTs, HR=0.79) (Interaction p=0.69). There was no evidence that any patient subgroup defined by age, sex, stage or histology benefited more or less from CT. The absolute benefit of CT at 12 months did vary according to WHO/ECOG (or equivalent) performance status. PS 0=8% (from 26% to 34%), PS 1=8% (from 18% to 26%), PS 2=5% (from 6% to 11%) and PS 3=4% (from 5% to 9%). Conclusion: The results demonstrate a substantial and consistent relative benefit of CT in advanced NSCLC. The effectiveness of newer agents such as navelbine, paclitaxel and gemcitabine (used as single agents) appears to be similar to that of cisplatin combined with older agents such as vindesine and mitomycin C. The absolute effect of CT varied according to performance status. No significant financial relationships to disclose.

Surgery and adjuvant chemotherapy (CT) compared to surgery alone in non-small cell lung cancer (NSCLC): A meta-analysis using individual patient data (IPD) from randomized clinical trials (RCT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7552-7552 ◽  
Author(s):  
L. A. Stewart ◽  
S. Burdett ◽  
J. F. Tierney ◽  
J. Pignon
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Alkylating Agents ◽  
Distant Recurrence ◽  
Rank Test ◽  
Patient Subgroup ◽  
Resected Nsclc ◽  
Hazard Ratios ◽  
Future Policy ◽  
Treatment Comparisons

7552 Background: A previous IPD meta-analysis (BMJ 1995;311:899) that suggested CT may have a role in the treatment of NSCLC has been updated. This includes RCTs, regimens and outcomes that were not available in 1995. The meta-analysis examines the role of CT in 7 treatment comparisons. Here we report on the effectiveness of surgery plus adjuvant CT compared with surgery alone. Methods: We conducted a systematic search for RCTs followed by the central collection, checking and re-analysis of updated IPD. Results from RCTs were combined using the stratified (by trial) log rank test to calculate individual and pooled hazard ratios (HRs). Previously included RCTs using long-term alkylating agents were excluded from this analysis due to their antiquity. Results: IPD were obtained on 8147 patients from 30 RCTs. 15 RCTs used a cisplatin combination without Tegafur/Tegafur+Uracil (UFT), 8 RCTs used Tegafur/UFT without cisplatin and 7 RCTs used Tegafur/UFT and cisplatin. This represents 95% of all known randomised patients and adds 18 trials and 5835 patients to the 1995 analyses. The results show a highly significant benefit of CT on survival (HR=0.86 95% CI 0.81–0.93, p<0.000001), with an absolute benefit of 4% (from 60% to 64%) at 5 years. Results were similar for recurrence-free survival and time to distant recurrence, but there was a larger effect on time to local recurrence ( Table ). There was no clear difference in effect by type of CT given. There was no clear evidence that any patient subgroup defined by age, sex or histology benefited more or less from CT. There was a suggestion of a trend in effect by stage (p=0.047), this will be explored further. Conclusion: The results demonstrate conclusively and consistently a benefit of adjuvant CT in resected NSCLC, irrespective of the regimen used, the patient subgroup treated or the endpoint assessed, thus providing reliable estimates on which to base future policy and research. [Table: see text] [Table: see text]

A Retrospective Comparison of Matched Elderly Patients Treated with Laromustine (Cloretazine®) or Best Supportive Care or Low Dose Ara-C in the LRF AML14 Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2960-2960 ◽  
Author(s):  
Robert Hills ◽  
Susan O’Brien ◽  
Verena Karsten ◽  
Alan K. Burnett ◽  
Francis Giles
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Low Dose ◽  
De Novo ◽  
Performance Status ◽  
Single Agent ◽  
Best Supportive Care ◽  
Cell Counts ◽  
Retrospective Comparison ◽  
De Novo Aml

Abstract Background : A substantial proportion of older patients with AML are considered unlikely to benefit from an intensive treatment approach. They often receive either best supportive care (BSC), low dose treatment such as Low Dose Ara-C (LDAC), or clinical trials of novel agents. In one of the few randomised studies where patients were prospectively considered likely to be unfit for intensive therapy, LDAC was superior to BSC with 18% v 1% patients achieving CR. No patients with high risk cytogenetics (Grimwade 1998), achieved CR (Burnett 2007). Laromustine (Cloretazine®) is a novel sulfonylhydrazine alkylating agent which preferentially targets the O6 position of guanine resulting in DNA cross-links. Laromustine has previously shown clinical activity in patients with de novo AML and high risk MDS (Giles et al. JCO 2007). A confirmatory phase II study of single agent laromustine was conducted in previously untreated patients ≥ 60 years old with de novo AML, prospectively considered likely to be unfit for intensive chemotherapy. Patients had at least one poor risk factor, defined by age ≥70, performance status 2, unfavorable cytogenetics, or cardiac, pulmonary or hepatic dysfunction. Eighty-five patients received induction therapy with 600 mg/m2 laromustine. Second induction cycles were administered in 14 patients after partial response or hematologic improvement. Eighteen patients received at least one consolidation cycle of cytarabine 400 mg/m2/day CIV for 5 days. Methods: A retrospective non-randomised comparison was performed between the 85 patients treated with laromustine, and 121 patients satisfying the same entry criteria, treated in the AML 14 trial with either BSC or LDAC. Outcomes were compared using Mantel-Haenszel and logrank methods for unadjusted comparisons, and regression methods for adjusted analyses. Results : Patients in AML14 were slightly older than those treated with laromustine (median age 75 v 73), and tended to have higher white blood cell counts; by contrast, there were significantly fewer cardiac or respiratory comorbidities reported in the AML14 population. Other important risk factors such as performance status and cytogenetics were similar between the groups. Responses overall (CR/CRp) were seen in 33% (28/85) of patients treated with laromustine, compared with 2% (1/60) and 23% (14/61) in patients treated with BSC and LDAC (p&lt;0.0001, p=0.2, respectively). In particular, 1 patient with −5/del(5q), and 3 patients with −7/del(7q) cytogenetics experienced a CR with laromustine; patients in AML 14 with adverse cytogenetics saw no remissions. Survival was significantly improved in the laromustine group compared to BSC (1 year survival 20% v 8%, unadjusted HR 0.58 [0.40–0.84] p=0.004), and roughly comparable to that of LDAC (1 year survival 20% v 25%, HR 1.04 [0.73–1.49] p=0.8). Analyses adjusted for differences in baseline demographics, and using propensity scores gave consistent figures. Conclusions: Retrospective comparison of unrandomised data has significant limitations even though care has been taken to match for factors known to be predictive for survival. Laromustine was able to achieve a higher CR rate than LDAC or BSC, and produced remissions in groups where no remissions have previously been seen with LDAC or BSC. Laromustine gave significantly better survival than BSC, and demonstrated similar survival to LDAC.

Predictors of benefits to chemoimmunotherapy (CIT) in stage IV non-small-cell lung cancer (NSCLC): A meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20595-e20595
Author(s):  
Hazem Edmond El-Osta ◽  
Anita Lyn Sabichi
Keyword(s):  
Liver Metastasis ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Performance Status ◽  
Random Effect ◽  
Single Agent ◽  
Random Effect Model ◽  
Phase Iii ◽  
Smoking History ◽  
Metastatic Nsclc

e20595 Background: Immune checkpoint inhibitors (ICIs) have changed the landscape of NSCLC therapy. In previous study, gender, smoking history, and PD-L1 status were found to influence the efficacy of ICI monotherapy in NSCLC. This meta-analysis evaluated the clinical and molecular factors predictive of benefit from the addition of ICIs to first-line (1L) chemotherapy in metastatic NSCLC. Methods: Using the random effect model, we computed and compared the pooled hazard ratio (HR) of progression-free survival (PFS) and overall survival (OS) among the selected subgroups. The correlation between PD-L1 expression level and outcome was analyzed by meta-regression. Results: 7 phase III randomized trials comparing CIT vs. chemo in the 1L treatment of stage 4 NSCLC were included. CIT evenly improved the PFS irrespective of age, gender, histology, smoking history and ECOG performance status (PS). While patients (pts) with liver metastasis or ALK/EGFR aberration had greater PFS with the addition of ICI to Bevacizumab (BEV) based chemo regimen, the derived benefit was no longer statistically significant among pts treated with non-BEV-based regimens. Whereas the PFS superiority conferred by CIT was noticed across all PD-L1 expression subgroups, the benefit correlated with PD-L1 level and was more pronounced in the “PD-L1 high” subset. Except for pts with EGFR/ALK abnormalities, squamous histology or liver metastasis, CIT yielded a consistent amelioration of OS across the other selected subgroups. Conclusions: Survival advantage associated with 1L CIT in metastatic NSCLC was observed in different pts population including those for which single-agent ICI has limited therapeutic benefit. Our findings support the role of chemo +/- VEGF blockade as enhancer of ICIs activity even in “less immunogenic” context. [Table: see text]

Single Agent Sequential Chemotherapy in Non-Hodgkin's Lymphomas

1973 ◽  
Vol 59 (3) ◽  
pp. 219-238 ◽  
Author(s):  
Silvio Monfardini ◽  
Gabriele Tancini ◽  
Marco Gasparini ◽  
Federico Pizzetti ◽  
Mario De Lena ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Median Survival ◽  
Alkylating Agents ◽  
Performance Status ◽  
Single Agent ◽  
Sequential Chemotherapy ◽  
Clinical Resistance ◽  
Extranodal Disease ◽  
Well Differentiated ◽  
Hodgkin's Lymphomas

A retrospective analysis of 118 patients with non-Hodgkin's lymphomas who received one or more drugs of single agent chemotherapy was conducted to determine the relationship between the histopathologic category of lymphoma, based on the classification proposed by Rappaport et al., and the results (type of regression and survival) of sequential chemotherapy. In 96/118 cases, slides were available for histopathologic reclassification. Patients were selected according to the following criteria: chemotherapy with single agents administered in sequence (e.g. alkylating agents, vincristine, adriamycin, bleomycin); change in drug administration only after an adequate course and either no response or clinical resistance after prior regression; measurable disease; performance status greater than 40. Prior to chemotherapy 66 patients had diffuse (extranodal) disease, 39 adenopathies above and below the diaphragm, and 13 adenopathies only above or below the diaphragm. 49/118 patients were pretreated with radiotherapy. The data were most complete for alkylating agents which were administered as a single agent in 93 patients. Complete remission (CR) plus partial remission (PR) greater than 50% occurred in 39% of patients with lymphocytic lymphoma, in 39% with histiocytic and in 50% with mixed type lymphoma (table 4). This type of response was observed with all drugs in 70% of nodular lymphomas and in 36% of diffuse lymphomas (table 7). The overall response rate to adriamycin was 75% in nodular lymphomas, and 55% in diffuse lymphomas. These data were 40% and respectively 14% after treatment with bleomycin. Median survival of all non-Hodgkin's lymphomas was 16.2 months (fig. 1); median survival was 23.4 months for nodular lymphomas and 17.4 months for diffuse lymphomas (fig. 2). Among nodular lymphomas, no significant differences were observed between nodular histiocytic and nodular lymphocytic well differentiated (fig. 3). Diffuse lymphocytic well differentiated lymphomas showed better survival in comparison to diffuse lymphocytic poorly differentiated, diffuse histiocytic and diffuse undifferentiated types (fig. 4). Patients responding to 2 drugs or more showed a better median survival (66 months) than those responding only to one drug (22.4 months) and unresponsive patients (10.2 months) (fig. 5). This study confirms most of the data reported by the Stanford group and emphasizes the need to employ a more deteailed histopathologic classification such as that proposed by Rappaport et al. Although this retrospective analysis has a number of drawbacks, it does provide, in terms of survival, a measurable indication that the responsiveness to at least two drugs is associated with better survival in non-Hodgkin's lymphomas than little or no responsiveness.

Surgery (S) and radiotherapy (RT) plus adjuvant chemotherapy (CT) versus surgery and radiotherapy in non-small cell lung cancer (NSCLC): A meta-analysis using individual patient data (IPD) from randomised clinical trials (RCTs)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7521-7521 ◽  
Author(s):  
C. Le Pechoux ◽  
H. Tribodet ◽  
J. P. Pignon ◽  
S. Burdett
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Meta Analysis ◽  
Alkylating Agents ◽  
Vinca Alkaloid ◽  
Distant Recurrence ◽  
Rank Test ◽  
Incomplete Resection ◽  
Number Of Patients ◽  
Future Policy

7521 Background: Our previous IPD meta-analysis of CT (BMJ 1995;311:899) suggested that CT may have a role in the treatment of various stages of NSCLC. However, the results in the S + RT setting were uncertain because of the small number of patients in this setting. We have updated this meta-analysis, including trials and outcomes not available in 1995. We report here on the effectiveness of S+RT+CT compared to S+RT. Methods: Systematic searches for RCTs were followed by the central collection, checking and re-analysis of updated IPD. Results from individual trials were combined using the stratified (by trial) log rank test to calculate pooled hazard ratios (HRs). Previously included old trials using long-term alkylating agents were excluded from this analysis. Results: IPD were obtained from 2,626 patients (12% with incomplete resection) from 11 RCTs. This represents 86% of all known randomised patients and adds a further 5 trials and 1,956 patients to the 1995 analyses. Median follow-up is 6.3 years. Ten trials used sequential RT-CT. 8 RCTs used cisplatin + vinca alkaloid/ etoposide, 1 used cisplatin + tegafur and 2 used other platinum regimens. There is a significant benefit of CT on survival (HR=0.88, 95% CI=[0.80–0.96], p=0.0062), with an absolute benefit of 4.7% (from 29% to 34%) at 5 years. The HRs for older (0.93 [0.79–1.10]) and more recent trials (0.89 [0.81–0.97]) were comparable (test for interaction p=0.49). Results were similar for recurrence-free survival (0.84, [0.77–0.93], p=0.0006), local (0.79 [0.67–0.94], p=0.0075) and distant recurrence-free interval (0.75 [0.66–0.87], p<0.0001) (data available for 7 trials). There was no clear evidence of a difference in effect by type of CT given. Also, there was no clear evidence that any patient subgroup defined by age, sex or stage benefited more or less from CT. Conclusion: These results demonstrate now a benefit of adjuvant chemotherapy in resected lung cancer associated with radiotherapy. These results are very similar to those of the meta-analysis without radiotherapy. They provides robust estimates for future policy and research. Unrestricted grants from PHRC, LNCC and sanofi-aventis. [Table: see text]

Prognostic and predictive factors for overall survival (OS) in metastatic esophagogastric cancer (EGC): A meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4048-4048 ◽  
Author(s):  
Emil ter Veer ◽  
Jessy Joy van Kleef ◽  
Sandor Schokker ◽  
Stephanie Van Der Woude ◽  
Marety Laarman ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Predictive Factors ◽  
Meta Analysis ◽  
Performance Status ◽  
Disease Stage ◽  
First Line ◽  
Measurable Disease ◽  
Treatment Comparisons ◽  
Metastatic Sites ◽  
Prognostic And Predictive Factors

4048 Background: Prognostic and predictive factors for metastatic EGC are important to estimate prognosis, inform clinical decision-making and design future trials. We performed a systematic review with meta-analysis to identify these factors. Methods: We searched Medline, EMBASE and CENTRAL for phase 2/3 randomized controlled trials (RCTs) until January 2016 on palliative chemotherapy and targeted therapy for metastatic EGC. Prognostic and predictive factors were identified from respectively multivariate cox regressions and stratified treatment comparisons. Hazard Ratio’s (HR) for OS were extracted and pooled with meta-analysis if possible. Prognostic factors were considered independent if the multivariate HR was significant (P≤0.05). Predictive factors were clinically relevant if P for subgroup interaction was ≤0.20 and the HR in one of the subgroups was significant (P≤0.05). Results: We identified 47 RCTs (14,853 patients), wherein 54 potential prognostic and 40 predictive factors were reported. Eight independent prognostic factors for poor OS reported in ≥2 RCTs based on ≥300 patients were: performance status of ≥1 vs 0 (pooled HR, 95% confidence interval: 1.47, 1.25-1.73) or 2 vs 0-1 (1.52, 1.32-1.76); metastatic vs locally advanced disease (1.55, 1.39-1.72); diffuse vs intestinal/other histology (1.38, 1.12-1.71); ≥3 vs < 2 metastatic sites (1.35, 1.07-1.70); presence of metastases in peritoneum (1.24, 1.01-1.51) or liver (1.45 (1.28-1.64); measurable vs non-measurable disease (1.31, 1.04-1.66); and no prior vs prior surgery (1.33, 1.16-1.53). Predictive factors for specific treatment comparisons based on ≥300 patients were: age (≥65 vs < 65); performance status; tumor location (GEJ vs stomach); disease stage; number of metastatic sites; peritoneal metastasis; measurable disease; histology; HER2; KRAS; VEGF A; and Neuropilin-1 for first line treatments; and time to progression on first line therapy ( < 3, 3-6 or ≥6 months) for second-line treatments. Conclusions: Eight independent prognostic factors for OS and thirteen clinically relevant predictive factors for treatment efficacy of EGC were found.

Neoadjuvant multimodal treatment of borderline resectable (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) in Mexico.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 454-454
Author(s):  
Vanessa Rosas Camargo ◽  
Edgar Omar Martos Armedáriz ◽  
Miriam Heidi Cisneros Cordero ◽  
ZULEYMA NIETO GARCIA ◽  
Christian Haydeé Flores Balcázar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Multimodal Treatment ◽  
Performance Status ◽  
Univariate Analysis ◽  
Single Agent ◽  
Locally Advanced ◽  
Pancreatic Head ◽  
Rank Test ◽  
R0 Resection

454 Background: Pancreatic cancer remains a highly lethal disease. There is no consensus on treatment sequences and chemotherapy (CT) regimen in BRPC and LAPC. Our aim was to describe the multimodal treatment and outcomes in our population. Methods: We retrospectively reviewed medical records of patients (pts) with BRPC/LAPC and histological diagnosis of adenocarcinoma evaluated at Instituto Nacional de Ciencias Médicas y Nutrición from January 2011-December 2016. Clinical and pathological variables at diagnosis and treatment were recorded. Overall survival (OS) was estimated using Kaplan-Meier method and compared by Log-rank test. Results: 69 pts were evaluated, 39% (27) did not receive treatment. We analyze 42 treated pts. BRPC 33%/LAPC 67%. Median age was 58.8 y/o, 54.8% were female. Symptoms at diagnosis: 79% abdominal pain, 76% weight loss, 55% jaundice. ECOG performance status (PS): 0 (17%), 1 (69%) and 2 (14%). Main location was pancreatic head (76%). Median laboratory values: total bilirubin 1.04 mg/dL (0.2-25), albumin 4.1 g/dL (2.4-5.1), CA 19.9 182.8 U/mL (0.8-4028). Laparotomy at diagnosis was performed in 21%. All pts received induction CT (iCT). FOLFIRINOX was the most common regimen (37%), followed by FOLFOX4 (34%). The best overall response with iCT was stable disease (62%), progressive disease was observed in 24%. iCT followed by chemoradiation (CRT) could be delivered to 48% (20/42). Capecitabine-based CRT was preferred (94%). Six pts (14%) underwent surgical resection after multimodal treatment (36% BRPC, 3.5% LAPC), 5 pts achieved R0 resection. The resection rate with single-agent iCT was 0% vs 20% with combination iCT. Median OS was 15.6 months (m): 14.4 m for BRPC and 15.5 m for LAPC. Median OS according iCT: gemcitabine 7.8 m, fluorouracil 13.7 m, FOLFOX4 15.5 m and FOLFIRINOX 24.6 m. Univariate analysis identified ECOG PS (0-1 vs 2, P = 0. 014) and age ( < 59 vs ³59, P = 0.002) as significantly associated with survival. Conclusions: Early administration of combination CT followed by CRT and/o surgical resection in selected pts improves oncological outcomes in pts with BRPC/LAPC. In pts with good PS, iCT with FOLFIRINOX is the preferred regimen given best results.

scholarly journals Many continuous variables should be analyzed using the relative scale: a case study of β2-agonists for preventing exercise-induced bronchoconstriction

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Harri Hemilä ◽  
Jan O. Friedrich
Keyword(s):  
Meta Analysis ◽  
Relative Effect ◽  
Similar Amount ◽  
Mixed Effect ◽  
Absolute Scale ◽  
Effect Model ◽  
Absolute Effect ◽  
The Absolute ◽  
Relative Scale ◽  
Exercise Induced

Abstract Background The relative scale adjusts for baseline variability and therefore may lead to findings that can be generalized more widely. It is routinely used for the analysis of binary outcomes but only rarely for continuous outcomes. Our objective was to compare relative vs absolute scale pooled outcomes using data from a recently published Cochrane systematic review that reported only absolute effects of inhaled β2-agonists on exercise-induced decline in forced-expiratory volumes in 1 s (FEV1). Methods From the Cochrane review, we selected placebo-controlled cross-over studies that reported individual participant data (IPD). Reversal in FEV1 decline after exercise was modeled as a mean uniform percentage point (pp) change (absolute effect) or average percent change (relative effect) using either intercept-only or slope-only, respectively, linear mixed-effect models. We also calculated the pooled relative effect estimates using standard random-effects, inverse-variance-weighting meta-analysis using study-level mean effects. Results Fourteen studies with 187 participants were identified for the IPD analysis. On the absolute scale, β2-agonists decreased the exercise-induced FEV1 decline by 28 pp., and on the relative scale, they decreased the FEV1 decline by 90%. The fit of the statistical model was significantly better with the relative 90% estimate compared with the absolute 28 pp. estimate. Furthermore, the median residuals (5.8 vs. 10.8 pp) were substantially smaller in the relative effect model than in the absolute effect model. Using standard study-level meta-analysis of the same 14 studies, β2-agonists reduced exercise-induced FEV1 decline on the relative scale by a similar amount: 83% or 90%, depending on the method of calculating the relative effect. Conclusions Compared with the absolute scale, the relative scale captures more effectively the variation in the effects of β2-agonists on exercise-induced FEV1-declines. The absolute scale has been used in the analysis of FEV1 changes and may have led to sub-optimal statistical analysis in some cases. The choice between the absolute and relative scale should be determined based on biological reasoning and empirical testing to identify the scale that leads to lower heterogeneity.

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