Time-lag Bias in Trials of Pediatric Antidepressants: a Systematic Review and Meta-analysis

Overview

Journal J Am Acad Child Adolesc Psychiatry

Publisher Elsevier

Specialties Pediatrics
Psychiatry

Date 2010 Dec 16

PMID 21156271

Citations 12

Authors

Magdalena M Reyes

Kaitlyn E Panza

Andres Martin

Michael H Bloch

Affiliations

Soon will be listed here.

Abstract

Objective: To determine whether there is evidence of a time-lag bias in the publication of pediatric antidepressant trials.

Method: We conducted a meta-analysis of published and unpublished randomized placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years of age with major depressive disorder. Our main outcomes were (1) time to publication of positive versus negative trials, and (2) proportion of treatment responders in trials with standard (<3 years after study completion) versus delayed publication.

Results: We identified 15 randomized, placebo-controlled trials of SRIs for pediatric depression. Trials with negative findings had a significantly longer time to publication (median years ± standard deviation = 4.2 ± 1.9) than trials with positive findings (2.2 ± 0.9; log-rank χ(2) = 4.35, p = .037). The estimated efficacy in trials with standard publication time (number needed to treat = 7, 95% CI = 5-11) was significantly greater than those with delayed publication (17, 95% CI = 9-∞; χ(2) = 4.98, p = .025). The inflation-adjusted impact factor of journals for published trials with positive (15.33 ± 11.01) and negative results (7.54 ± 7.90) did not statistically differ (t = 1.4, df = 10, p = .17).

Conclusions: Despite a small number of trials of SRIs for pediatric antidepressants, we found a significant evidence of time-lag bias in the publication of findings. This time-lag bias altered the perceived efficacy of pediatric antidepressants in the medical literature. Time-lag bias is not unique to child psychiatry and reflects a larger problem in scientific publishing.

Citing Articles

Time to publication for results of clinical trials.

Showell M, Cole S, Clarke M, DeVito N, Farquhar C, Jordan V Cochrane Database Syst Rev. 2024; 11():MR000011.

PMID: 39601300 PMC: 11600493. DOI: 10.1002/14651858.MR000011.pub3.

Need for Speed: Investigating Publication Times and Impact Factors of Plastic Surgery Journals.

Chawla S, Shelly S, Phord-Toy R, Khosa F Plast Reconstr Surg Glob Open. 2021; 9(10):e3838.

PMID: 34616641 PMC: 8489889. DOI: 10.1097/GOX.0000000000003838.

Interventions to Reduce Medication Dispensing, Administration, and Monitoring Errors in Pediatric Professional Healthcare Settings: A Systematic Review.

Koeck J, Young N, Kontny U, Orlikowsky T, Bassler D, Eisert A Front Pediatr. 2021; 9:633064.

PMID: 34123962 PMC: 8187621. DOI: 10.3389/fped.2021.633064.

Interventions to Reduce Pediatric Prescribing Errors in Professional Healthcare Settings: A Systematic Review of the Last Decade.

Koeck J, Young N, Kontny U, Orlikowsky T, Bassler D, Eisert A Paediatr Drugs. 2021; 23(3):223-240.

PMID: 33959936 DOI: 10.1007/s40272-021-00450-6.

Registry versus publication: discrepancy of primary outcomes and possible outcome reporting bias in child and adolescent mental health.

Vrljicak Davidovic N, Komic L, Mesin I, Kotarac M, Okmazic D, Franic T Eur Child Adolesc Psychiatry. 2021; 31(5):757-769.

PMID: 33459886 DOI: 10.1007/s00787-020-01710-5.

References

Simeon J, DiNicola V, Ferguson H, Copping W . Adolescent depression: a placebo-controlled fluoxetine treatment study and follow-up. Prog Neuropsychopharmacol Biol Psychiatry. 1990; 14(5):791-5. DOI: 10.1016/0278-5846(90)90050-q. View

Turner E, Matthews A, Linardatos E, Tell R, Rosenthal R . Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008; 358(3):252-60. DOI: 10.1056/NEJMsa065779. View

Dickersin K, Olson C, Rennie D, Cook D, Flanagin A, Zhu Q . Association between time interval to publication and statistical significance. JAMA. 2002; 287(21):2829-31. DOI: 10.1001/jama.287.21.2829. View

Churchill R, Hunot V, Corney R, Knapp M, McGuire H, Tylee A . A systematic review of controlled trials of the effectiveness and cost-effectiveness of brief psychological treatments for depression. Health Technol Assess. 2002; 5(35):1-173. DOI: 10.3310/hta5350. View

Wagner K, Jonas J, Findling R, Ventura D, Saikali K . A double-blind, randomized, placebo-controlled trial of escitalopram in the treatment of pediatric depression. J Am Acad Child Adolesc Psychiatry. 2006; 45(3):280-288. DOI: 10.1097/01.chi.0000192250.38400.9e. View

Keller M, Ryan N, Strober M, Klein R, Kutcher S, Birmaher B . Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry. 2001; 40(7):762-72. DOI: 10.1097/00004583-200107000-00010. View

Hetrick S, Merry S, McKenzie J, Sindahl P, Proctor M . Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents. Cochrane Database Syst Rev. 2007; (3):CD004851. DOI: 10.1002/14651858.CD004851.pub2. View

Ioannidis J . Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials. JAMA. 1998; 279(4):281-6. DOI: 10.1001/jama.279.4.281. View

Hopewell S, Clarke M, Stewart L, Tierney J . Time to publication for results of clinical trials. Cochrane Database Syst Rev. 2007; 2):MR000011. PMC: 7437393. DOI: 10.1002/14651858.MR000011.pub2. View

10.

von Knorring A, Olsson G, Thomsen P, Lemming O, Hulten A . A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder. J Clin Psychopharmacol. 2006; 26(3):311-5. DOI: 10.1097/01.jcp.0000219051.40632.d5. View

11.

Ulas H, Binbay T, Alptekin K . [Financial conflict of interest in clinical psychiatry studies: a review]. Turk Psikiyatri Derg. 2008; 19(4):418-26. View

12.

Hopewell S, Loudon K, Clarke M, Oxman A, Dickersin K . Publication bias in clinical trials due to statistical significance or direction of trial results. Cochrane Database Syst Rev. 2009; (1):MR000006. PMC: 8276556. DOI: 10.1002/14651858.MR000006.pub3. View

13.

Emslie G, Rush A, Weinberg W, Kowatch R, Hughes C, Carmody T . A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry. 1997; 54(11):1031-7. DOI: 10.1001/archpsyc.1997.01830230069010. View

14.

Krzyzanowska M, Pintilie M, Tannock I . Factors associated with failure to publish large randomized trials presented at an oncology meeting. JAMA. 2003; 290(4):495-501. DOI: 10.1001/jama.290.4.495. View

15.

Zanarini M, Frankenburg F . omega-3 Fatty acid treatment of women with borderline personality disorder: a double-blind, placebo-controlled pilot study. Am J Psychiatry. 2002; 160(1):167-9. DOI: 10.1176/appi.ajp.160.1.167. View

16.

Bridge J, Iyengar S, Salary C, Barbe R, Birmaher B, Pincus H . Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007; 297(15):1683-96. DOI: 10.1001/jama.297.15.1683. View

17.

Hirsch L . Trial registration and results disclosure: impact of US legislation on sponsors, investigators, and medical journal editors. Curr Med Res Opin. 2008; 24(6):1683-9. DOI: 10.1185/03007990802114849. View

18.

Emslie G, Ventura D, Korotzer A, Tourkodimitris S . Escitalopram in the treatment of adolescent depression: a randomized placebo-controlled multisite trial. J Am Acad Child Adolesc Psychiatry. 2009; 48(7):721-729. DOI: 10.1097/CHI.0b013e3181a2b304. View

19.

Mathieu S, Boutron I, Moher D, Altman D, Ravaud P . Comparison of registered and published primary outcomes in randomized controlled trials. JAMA. 2009; 302(9):977-84. DOI: 10.1001/jama.2009.1242. View

20.

Dickersin K, Min Y, Meinert C . Factors influencing publication of research results. Follow-up of applications submitted to two institutional review boards. JAMA. 1992; 267(3):374-8. View