| Internal validity | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Author Year | Randomization adequate? | Allocation concealment adequate? | Groups similar at baseline? | Eligibility criteria specified? | Outcome assessors masked? | Care provider masked? | Patient masked? | Reporting of attrition, crossovers, adherence, and contamination | Loss to follow-up: differential/high | Intention-to-treat (ITT) analysis | Post-randomization exclusions | Funding | Quality rating |
| Berger 2003 | NR | NR | Yes | Yes | Yes | NR | Yes | NR | No | Yes | Yes | Manufacturer funded | Fair |
| Berger 2006 Efficacy | Yes | NR | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes | Attrition reported (4%); crossover, adherence, contamination NR | No | No Not all randomized were in ITT (643/722 in some analyses) | No | Integrated Therapeutics Group, Inc. (a subsidy of Schering-Plough) | Fair |
| Berger 2006 Impact | Yes | Yes | NR | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes | Attrition reported (3.5%); crossover, adherence, contamination NR | No | No 354/360 in ITT | No | MedPointe Pharmaceuticals | Fair |
| Bachert 2009 | Yes | NR | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes | Attrition reported (6%);no crossover; adherence 100%; contamination NR | No | Yes | No | FAES FARMA, S.A., Spain | Fair |
| Bernstein 2004 | Method not reported | Method not reported | Yes | Yes | Yes | Yes | Yes | Attrition reported (13,6,9% in A, B, C) and adherence (97–99%) | No | No, as attrition 13,6,9% in A, B, C; analysis termed ‘ITT” as included all patients who were randomized | None | GlaxoSmithKline Inc., Research Triangle Park, NC | Fair |
| Bernstein 2009 | Yes | Method not reported | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | NR; study reported as “double blind” | Attrition reported (2.4%) | No | No 843/835 in ITT | NR J. Bernstein, B. Prenner, B. Ferguson, and J. Portnoy receive grant/research support from Meda Pharmaceuticals. J. Bernstein, B. Prenner, and B. Ferguson are consultants for Meda Pharmaceuticals. J. Bernstein and B. Prenner are also speakers for Meda Pharmaceuticals. W. Wheeler and H. Sacks are employees of Meda Pharmaceuticals | Fair | |
| Bhatia 2005 | Unclear, “randomization was assigned by a code in blocks of 4” | NR | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes, study drugs described as identical to placebo | Attrition 0; others NR | No | Yes; no attrition or exclusions post randomization | None | Study supported by a grant from the investigator sponsored Studies program of AstraZeneca, Westborough, Mass. | Fair |
| Ciprandi 1997 | Yes, method not reported | NR | Yes | Q4. Y | Q5. NR | NR | NR | NR | No | Yes | NR | Manufacturer funded | Fair |
| Ciprandi 2004 | Method not reported | NR | No difference on TSS, other characteristics not reported | yes (limited) | NR; study reported as “double blind” | NR; study reported as “double blind” | Assume yes (placebo-controlled) | no | NR | unable to determine (states “30 patients were evaluated”) but not clear if same as number randomized. | NR | NR | Poor baseline demographic characteristics NR, and randomization and allocation concealment methods NR- may be differences between groups at baseline, also unable to determine number analyzed. |
| Corren 2005 | Yes | Yes | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes, study drugs described as identical to placebo | Attrition 8/307; others NR | No | No (but only 1 patient with no post baseline data (AZE) not included in analysis) | 1 patient in each group was discontinued because of a protocol violation; 4 patients in B and 2 in a discontinued due to AEs | Acknowledgements includes 2 employees of Med Pointe Pharmaceuticals, Somerset, NJ (makers of Astelin®) | Good |
| Dockhorn 1987 | NR | NR | Yes | Yes | Yes | NR | Yes | NR | No | Yes | Yes | Manufacturer funded | Fair |
| Hampel 2003 | NR | No | Yes | Yes | Yes | NR | Yes | NR | No, none | Yes | NR | Manufacturer funded | Fair |
| Hampel 2004 | Method not reported | Method not reported | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes; study drugs described as identical to placebo | Attrition reported (100/749); others NR | No (100/749=13.3%) | No; attrition=100/749; analyzed all patients who took at least one dose of study medication | Yes: 25 (3.3%) excluded for protocol violation | NR; Aventis Pharmaceuticals, Inc. is the affiliation of one of the investigators | Fair |
| Horak 2004 | Method not reported | Method not reported | NR | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes, study drugs described as identical to placebo | Attrition reported (20/120) | No | No; drop-outs 20; some post randomization exclusions, per protocol analysis | Yes: 8 patients excluded for protocol violations, 11 patients excluded as no nasal symptoms at baseline | NR; last author affiliated with Saluc Pharma SA, Prangins, VD (Switzerland) | Poor - not ITT; post- randomization exclusions; NR if groups similar at baseline. |
| Howarth 1999 | NR | NR | Yes | Yes | Yes | NR | Yes | NR | No | No | Yes | Manufacturer funded | Fair |
| Kurowski 2003 | Method not reported | Method not reported | Age and sex similar, other characteristics NR | Yes | NR; study reported as “double blind” | Yes, efforts taken to conceal study drug assignment from patients and providers | Yes, efforts taken to conceal study drug assignment from patients and providers | Attrition reported (12 patients did not complete study; others NR; also contamination- one patient took an OTC antihistamine | Yes (12/60=20%) | No; drop-outs 12, including 4 for lack of efficacy and 1 for protocol violation | 4 patients discontinued study for aggravation of symptoms: group A 2, B 1, D 1; 1 patient excluded for violation of protocol (took an OTC antihistamine) | Study supported by a grant from medical university of Lodz; study drugs supplied by UCB Pharma, Brussels, Belgium, Schering- Plough, Kenilworth, NJ, and MSD, Whitehouse Station NJ | Poor: high loss to f/u, not ITT, also limited baseline characteristics reported. |
| LaForce 1996 | NR | NR | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes; identical placebo given | Attrition reported (30/264 dropped), others NR | No | Yes | No | NR | Fair |
| Lumry 2007 | NR | NR | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | NR; study reported as “double blind” | Attrition reported (12/554 dropped), others NR | No | Yes | 2 were withdrawn for being noncompliant with protocol | Medpointe Pharmaceuticals | Fair |
| Martinez-Cocera 2005 | Yes: computer- generated scheme | Unclear; patients assigned to a sequential randomization number | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes, study drugs described as identical to placebo | Attrition 37/249; others NR | Yes (15%), but similar rates in both groups | No, as attrition; study termed ITT as primary analysis based on all patients receiving 1+ dose of study drug | Yes; 8 patients received no study medication (no explanation given) | Study partially supported by the National Scientific research program of the Spanish Ministry of Science and Technology | Fair |
| Meltzer 2005 | NR | NR | Yes | Yes | Unclear: stated as “double blind” | Unclear: stated as “double blind” | Unclear: stated as “double blind” | No/No/No/No | Unclear | Yes | No | Alcon Research | Fair |
| Meltzer 2006 | NR | NR | Yes | Yes | Unclear: stated as “double blind” | Unclear: stated as “double blind” | Unclear: stated as “double blind” | Yes/No/No/No | No/No | Yes | No | Schering-Plough Corp., France | Fair |
| Mahmoud 2008 | NR | NR | Yes | Yes | Unclear | Unclear | Unclear | No/No/No/No | Unclear | NR | NR | NR | Poor |
| Okubo 2004, 2005 | Method not reported | Method not reported | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | NR; study reported as “double blind” | Attrition reported (3/210 in Okubo 2004, 4 in Okubo 2005); others NR | No (3 or 4/210) | No; attrition=3 or 4 | Yes: 3 did not complete HRQOL questionnaire, 1 received rescue medication (Okubo 2005; note Okubo 2004 states only 3 exclusions) | NR | Fair |
| Pradalier 2006 | Yes | NR | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | NR; study reported as “double blind” | NR Not clearly reported | NR | No 483/534 in ITT | Yes 51/534 (9.6%) excluded for not meeting inclusion criteria | Schering-Plough Corp., France | Fair |
| Prenner 2000 | NR | NR | Yes | Yes | Yes | NR | Yes | NR | No | Yes | No | Manufacturer funded | Fair |
| Ratner 2004 | Method not reported | Method not reported | No, C had lower mean years with allergy (p=0.015); NSD for TSS or individual symptom scores at baseline; placebo had fewer mean years with allergy (16 vs 19) | Yes | NR; study reported as ‘double blind” | NR; study reported as ‘double blind” | Yes | Attrition or exclusions 12.5%; overall compliance 95.2% | No, 87.5% of 703 completed the study | No- ITT defined as all patients who took at least one dose of study medication; not clear how many did not. | Exclusions for protocol violation [41 patients (5.8%)], treatment failure (15 patients). | NR | Fair |
| Saint-Martin 2004 | Method not reported | Method not reported | Yes | Yes | NR; study reported as ‘double blind” | NR; study reported as ‘double blind” | NR; study reported as ‘double blind” | Attrition reported; cross-overs, adherence, and contamination NR | Yes: 25% overall withdrawn, 31% in R20 vs 23.2% R10, and 20.7% L10 | No, exclusions for protocol violation and patients discontinued for other reasons (total 24.8% lost to follow-up); Reports both ITT and per protocol: 255/347 analyzed per protocol (73.4%) | Yes: 65 patients excluded for major protocol deviations: forbidden treatment, diary cards badly filled, un-allowed range between visits, exclusion criteria, treatment allocation mistake, lack of compliance); yes; 8/347 did not start treatment and were excluded | NR: lead author affiliation Association National de Formation continue en alklergologie, France, and secondary author affiliation: clinical Research Unit, Research Centre, J. Uriach & Cia S.A., Barcelona, Spain | Fair |
| Shah 2009 | Yes; Computer generated and blocked | Yes | Yes | Yes | Yes | Yes | Yes | Reports withdrawals based on AEs but others NR | Unclear | Modified ITT | Unclear | Alcon Research Ltd | Fair |
| Storms 1994 | NR | NR | Yes | Yes | NR; stated “double dummy” | NR; stated “double dummy” | Yes; identical placebo given | Attrition reported (2/245 dropped), others NR | No | Yes | No | NR | Fair |
| Ratner 1994 | NR | NR | No statistical difference, but more men in azelastine NS bid group compared to other groups | Yes | NR; stated “double dummy” | NR; stated “double dummy” | Yes; identical placebo given | Attrition reported (2/251 dropped), others no | No | Yes | No | Wallace laboratories | Fair |
| Ratner 2005 | NR | NR | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes; identical placebo given | NR; but analysis done on whole group | NR | Yes | Yes; 2 patients withdrawn because they enrolled at 2 sites | Alcon Research Ltd | Fair |
| UCB NCT00160537, A monocenter, double-blind… | Method not described | Not described | NR | Yes | Unclear, described as double blind | Unclear, described as double blind | Unclear, described as double blind | Attrition reported, none of others reported | No | Unclear, but low attrition | No | UCB | Fair |
| UCB, NCT00160589, A multicentre, double-blind… | Method not described | Not described | NR | Yes | Unclear, described as double blind | Unclear, described as double blind | Unclear, described as double blind | Attrition reported, none of others reported | More dropouts in placebo group | Yes | No | UCB | Fair |
| UCB NCT00525278, Study evaluating the efficacy… | Method not described | Not described | NR | Yes | Unclear, described as investigator blinded | Unclear, described as investigator blinded | Unclear, described as investigator blinded | Attrition reported, none of others reported | No | Unclear, but low attrition | No | UCB | Fair |
| UCB, NCT00521040, Evaluation of the efficacy… | Method not described | Not described | NR | Yes | Unclear, described as double blind | Unclear, described as double blind | Unclear, described as double blind | Attrition reported, none of others reported | yes, 85% | No, 3 patients excluded from analysis | Unclear | UCB | Poor |
| van Adelsberg 2003 | Method not reported | Method not reported | Yes | Yes | NR; study reported as “double blind” | NR; study reported as “double blind” | Yes, study drugs described as identical to placebo | Attrition reported (79/1079); others NR | No | No-ITT defined as all patients who had a baseline and at least one post-treatment assessment. | Patients discontinued the study for adverse clinical experience, laboratory adverse experience, or lack of efficacy A: 5.6% B: 6.3% C: 9.1% | Study supported by a grant from Merck Research Laboratories, Rahway NJ; first author’s affiliation is also Merck Research Laboratories | Fair Authors note that study powered for drug-placebo comparisons, not Loratadine to Monolukast |
| van Cauwenberge 2000 | NR | NR | Yes | Yes | Yes | NR | Yes | Yes/No/No/Yes | No | Yes | Yes | Manufacturer funded | Fair |
From: Evidence Tables
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