Dataset Information

Validity of sample sizes in publications of randomised controlled trials on the treatment of age-related macular degeneration: cross-sectional evaluation.

ABSTRACT:

Objective

The aim of this cross-sectional study was to examine the completeness and accuracy of the reporting of sample size calculations in randomised controlled trial (RCT) publications on the treatment of age-related macular degeneration (AMD).

Methods

A sample of 97 RCTs published between 2004 and 2014 was reviewed for the calculation of their sample size. It was examined whether a (complete) description of the sample size calculation was presented. Furthermore, the sample size was recalculated, whenever possible based on the published details, in order to verify the reported number of patients.

Primary outcome measure

The primary endpoint of this cross-sectional investigation was a described sample size calculation that was reproducible, complete and correct (maximum tolerated deviation between reported and replicated sample size ±2 participants per trial arm).

Results

A total of 50 publications (52%) did not provide any information on the justification of the number of patients included. Only 17 publications (18%) provided all the necessary parameters for recalculation; 8 of 97 (8%, 95%-CI: 4% to 16%) publications achieved the primary endpoint. The median relative deviation between reported and recalculated sample sizes was 1%, with a range from -43% to +66%.

Conclusion

Although a transparent sample size legitimation is a crucial determinant of an RCT's methodological validity, more than half of the RCT publications considered failed to report them. Furthermore, reported sample size legitimations were often incomplete or incorrect. In summary, clinical authors should pay more attention to the transparent reporting of sample size calculation, and clinical journal reviewers may opt to reproduce reported sample size calculations.

Synopsis

More than half of the analysed RCT publications on the treatment of AMD did not report a transparent sample size calculation. Only 8% reported a complete and correct sample size calculation.

SUBMITTER: Tulka S

PROVIDER: S-EPMC6797239 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Validity of sample sizes in publications of randomised controlled trials on the treatment of age-related macular degeneration: cross-sectional evaluation.

Tulka Sabrina S Geis Berit B Baulig Christine C Knippschild Stephanie S Krummenauer Frank F

BMJ open 20191010 10

<h4>Objective</h4>The aim of this cross-sectional study was to examine the completeness and accuracy of the reporting of sample size calculations in randomised controlled trial (RCT) publications on the treatment of age-related macular degeneration (AMD).<h4>Methods</h4>A sample of 97 RCTs published between 2004 and 2014 was reviewed for the calculation of their sample size. It was examined whether a (complete) description of the sample size calculation was presented. Furthermore, the sample siz ...[more]

PMID: 31601589

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Project description:To evaluate the association between pseudodrusen and incidence of late age-related macular degeneration (AMD) in fellow eyes of patients with unilateral neovascular AMD (nAMD).Cohort study within the Comparison of AMD Treatments Trials (CATT).Patients with neither nAMD nor geographic atrophy (GA) in the fellow eye at baseline.Presence and type (dot, reticular, or confluent) of baseline pseudodrusen were assessed using digital color fundus photography (CFP) viewed under full color, green channel, and blue channel; red-free images; and fluorescein angiography (FA). Incidence of nAMD was based on monthly clinical examination and reading center evaluation of images at years 1 and 2. Incidence of GA was based on reading center evaluation of CFP and FA images at years 1 and 2. Associations of baseline pseudodrusen with incident nAMD and GA were summarized with adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs) from multivariate Cox models, with adjustment of covariates identified through backward stepwise selection.Incident nAMD and GA.Among 620 fellow eyes, 176 (28.4%) had baseline pseudodrusen (55% dot, 82% reticular, 35% confluent). Within 2 years, nAMD occurred in 54 eyes (30.7%) with pseudodrusen and in 72 eyes (16.2%) without pseudodrusen (aRR, 2.05; 95% CI, 1.43-2.93); GA occurred in 27 eyes (15.3%) with pseudodrusen and in 37 eyes (8.3%) without pseudodrusen (aRR, 1.89; 95% CI, 1.13-3.17); late AMD occurred in 73 eyes (41.5%) with pseudodrusen and in 101 eyes (22.8%) without pseudodrusen (aRR, 2.07; 95% CI, 1.51-2.83). Dot pseudodrusen were associated independently with nAMD (aRR, 2.53; 95% CI, 1.60-4.00), whereas confluent pseudodrusen were associated independently with GA (aRR, 4.35; 95% CI, 1.69-11.2). Eyes with pseudodrusen had increased incidence of late AMD regardless of whether the Age-Related Eye Diseases Study (AREDS) severity score was 2 (28.7% vs. 10.3%), 3 (34.9% vs. 13.7%), or 4 (50.5% vs. 32.0%).In fellow eyes of CATT participants, pseudodrusen were associated independently with a higher incidence of both nAMD and GA. Dot pseudodrusen were associated with nAMD, whereas confluent pseudodrusen were associated with GA. Pseudodrusen should be considered along with the AREDS severity score for predicting late AMD.

Project description:ImportanceSingle-nucleotide polymorphisms (SNPs) associated with the CFH, ARMS2, C3, LIPC, CFB, and C2 genes are associated with age-related macular degeneration (AMD); however, the association of these SNPs with angiographic features of neovascular AMD has been inconsistent in previous studies, and to date, no studies have addressed their association with features on optical coherence tomography.ObjectiveTo evaluate the influence of genotype of SNPs previously associated with AMD on the phenotype of neovascular lesions.Design, setting, and participantsParticipants for this cross-sectional study were recruited from the 1185 patients enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), a randomized clinical trial. Eligibility criteria for CATT specified that eyes have choroidal neovascularization and visual acuity between 20/25 and 20/320. A subgroup of 835 patients provided blood samples from July 2010 through September 2011 and were genotyped for the SNPs rs1061170 (CFH), rs10490924 (ARMS2),rs2230199 (C3), rs10468017 (LIPC), rs4151667 (CFB), rs547154 (C2) using TaqMan SNP genotyping assays. Data analysis was initiated in November 2013 and completed in January 2016.Main outcomes and measuresPretreatment ocular characteristics on fluorescein angiography (lesion type, area of neovascularization and total lesion, retinal angiomatous proliferation) and on time-domain optical coherence tomography (presence of intraretinal, subretinal, and subretinal pigment epithelium fluid; thickness at the foveal center of the retina, subretinal fluid, and subretinal tissue complex), visual acuity, and age.ResultsA total of 835 (73%) of 1150 CATT patients were genotyped. Mean age decreased with the number of risk alleles for CFH (P < .001), ARMS2 (P < .001), and C3 (P = .005). The following results were found as the number of risk alleles increased from 0 to 1 to 2. For CFH, mean total thickness decreased from 476 to 476 to 434 µm (P = .01; adjusted for age, sex, and smoking status). For ARMS2, the mean area of the total lesion increased from 2.0 to 2.8 to 2.4 mm2 (P = .03), the proportion with retinal angiomatous proliferation lesions increased from 8% to 10% to 12% (P = .05), and the proportion with intraretinal fluid increased from 72% to 71% to 82% (P = .008). For C3, the proportion with intraretinal fluid decreased from 78% to 69% to 64% (P = .001), and the mean retinal thickness decreased from 225 to 207 to 197 µm (P = .02).Conclusions and relevanceCFH, ARMS2, and C3 were associated with specific features of neovascularization at the time patients were enrolled in CATT. Previously identified associations of ARMS2 and CFH with type of choroidal neovascularization on fluorescein angiography were not confirmed. New associations with OCT features identified in CATT need confirmation to establish whether a true association exists.Trial registrationclinicaltrials.gov Identifier: NCT00593450.

Project description:ImportanceRecent reports suggest that cilioretinal arteries (CRAs) confer protection against developing advanced age-related macular degeneration (AMD).ObjectiveTo further characterize the association between the presence of a CRA and incidence of geographic atrophy (GA) or choroidal neovascularization (CNV).DesignThis cohort study constituted an ad hoc secondary analysis of data from the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and was performed at 44 clinical centers in the United States among participants in CATT with CNV in the study eye and without advanced AMD in the fellow eye at baseline. The presence of a CRA was determined by 2 graders, masked to clinical data, using color fundus photographs, red-free fundus photographs, and fluorescein angiography. The proportion with CRAs at baseline between the study eye with CNV and fellow eye without CNV was first compared. The association of a CRA with incidence of CNV or GA at 5 years among fellow eyes and with incidence of GA among study (treated) eyes was then assessed. In addition, the association of CRAs with the Age-Related Eye Disease Study severity scale among the fellow eyes at baseline was assessed. Data were collected from February 1, 2008, through April 30, 2015, and analyzed from July 1, 2018, through April 30, 2019.ExposuresPresence of a CRA.Main outcomes and measuresThe association between the presence of a CRA and incidence of CNV or GA at 5 years of follow-up.ResultsA total of 350 patients (700 eyes) (230 [65.7% women; mean [SD] age, 77 [7.2] years) were included in the analysis. Cilioretinal arteries were present in 67 of 345 (19.4%) fellow eyes without baseline CNV and 73 of 349 (20.9%) study eyes with baseline CNV (P = .60). Cilioretinal arteries in fellow eyes were not associated with incidence of CNV at 5 years (125 of 278 [45.0%] among eyes without CRAs and 30 of 67 [44.8%] among eyes with CRAs; P = .99) or with incidence of GA at 5 years (110 of 278 [39.6%] among eyes without CRAs and 25 of 67 [37.3%] among eyes with CRAs; P = .89). Cilioretinal arteries in study eyes were not associated with incidence of GA at 5 years (105 of 276 [38.0%] study eyes without CRAs and 26 of 73 [35.6%] study eyes with CRAs; P = .72).Conclusions and relevanceThe analysis did not find a protective association between CRAs and incidence of CNV or GA among CATT participants who had unilateral exudative AMD. Why these findings were different from those of previous publications is unclear but may be partially explained by the different techniques used to detect CRAs or by the baseline advanced disease in CATT participants.Trial registrationClinicalTrials.gov identifier: NCT00593450.

Project description:ObjectiveTo describe the effects of treatment for 1 year with ranibizumab or bevacizumab on macular morphology and the association of macular morphology with visual acuity (VA) in eyes with neovascular age-related macular degeneration (AMD).DesignProspective cohort study within a randomized clinical trial.ParticipantsParticipants in the Comparison of Age-related Macular Degeneration Treatments Trials.MethodsParticipants were assigned randomly to treatment with ranibizumab or bevacizumab on a monthly or as-needed schedule. Optical coherence tomography (OCT), fluorescein angiography (FA), color fundus photography (FP), and VA testing were performed periodically throughout 52 weeks. Masked readers graded images. General linear models were applied to evaluate effects of time and treatment on outcomes.Main outcome measuresFluid type and location and thickness by OCT, size, and lesion composition on FP, FA, and VA.ResultsIntraretinal fluid (IRF), subretinal fluid (SRF), subretinal pigment epithelium fluid, and retinal, subretinal, and subretinal tissue complex thickness decreased in all treatment groups. A higher proportion of eyes treated monthly with ranibizumab had fluid resolution at 4 weeks, and the difference persisted through 52 weeks. At 52 weeks, there was little association between the presence of fluid of any type (without regard to fluid location) and the mean VA. However, at all time points, eyes with residual IRF, especially foveal IRF, had worse mean VA (9 letters) than those without IRF. Eyes with abnormally thin (<120 μm) or thick (>212 μm) retinas had worse VA than those with normal thickness (120-212 μm). At week 52, eyes with larger neovascular lesions or with foveal scar had worse VA than eyes without these features.ConclusionsAnti-vascular endothelial growth factor (VEGF) therapy reduced lesion activity and improved VA in all treatment groups. At all time points, eyes with residual IRF had worse VA than those without. Eyes with abnormally thin or thick retinas, residual large lesions, and scar also had worse VA. Monthly ranibizumab dosing yielded more eyes with no fluid and an abnormally thin retina, although the long-term significance is unknown. These results have important treatment implications in eyes undergoing anti-VEGF therapy for neovascular AMD.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

Project description:PurposeTo evaluate the effect of intraocular pressure-lowering medications on treatment outcomes in the Comparison of AMD Treatments Trials.MethodsSecondary analysis of Comparison of AMD Treatments Trials data. Medication logs were reviewed for continuous 2-year use of agents that increased aqueous outflow (Group A: topical prostaglandins) or suppressed aqueous production (Group B: topical beta blockers and carbonic anhydrase inhibitors). Eyes were excluded if mixed-mechanism intraocular pressure-lowering agents or medications from more than one group were taken. Anatomical and vision responses to treatment at years 1, 2, and over the entire 2-year period in each group were compared with controls (no intraocular pressure-lowering medications).ResultsInclusion criteria were met by 28 Group A patients, 19 Group B patients, and 857 controls. After 2 years, the control group had a mean visual acuity improvement of +6.3 letters from baseline, compared with +3.5 letters in Group A (P = 0.38), and +13.8 letters in Group B (P = 0.052). Mean retinal thickness change from baseline was -54.9 μm in controls, -80.6 μm in Group A (P = 0.26), and -96.8 μm in Group B (P = 0.13). Mean total thickness change from baseline was -163 μm in controls, -180 μm in Group A (P = 0.63), and -238 μm in Group B (P = 0.08). In longitudinal analysis with adjustment by their baseline values, anti-vascular endothelial growth factor treatment drug and regimen, Group B had more visual acuity improvement (difference of 2.6 letters, 95% confidence interval: -3.4-8.5 letters), more reduction in the retinal thickness (-17.9 μm, 95% confidence interval: -36.5 to 0.7 μm), and total thickness from baseline (mean difference of -54.7 μm, 95% confidence interval: -103 to 6.2 μm) compared with the control group.ConclusionConcurrent aqueous suppressant use during anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration was associated with a trend toward greater reductions in retinal and total thickness as well as improved visual outcomes over 2 years. A similar effect was not observed to the same extent with agents that increase aqueous outflow. Because of the small sample size and secondary analysis, these findings must be cautiously interpreted and perhaps serve as a basis for future prospective studies.

Dataset Information

Validity of sample sizes in publications of randomised controlled trials on the treatment of age-related macular degeneration: cross-sectional evaluation.

Objective

Methods

Primary outcome measure

Results

Conclusion

Synopsis

Publications

Validity of sample sizes in publications of randomised controlled trials on the treatment of age-related macular degeneration: cross-sectional evaluation.

Similar Datasets

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