Skip to main content

Advertisement

SpringerLink
Log in

Evaluating publication bias for clinical trials supporting new dermatologic drug approvals from 2003 to 2018

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

The degree of publication bias and impact of the Food and Drug Administration Amendments Act (FDAAA) of 2007, which aimed to improve clinical trial transparency, has yet to be examined for recent dermatologic drugs. The objective of our study was to estimate the degree of publication bias for clinical trials supporting FDA approval of new dermatologic drugs. This retrospective cohort study examined all phase II and III efficacy trials supporting approval of new dermatologic drugs from 2003 to 2018. FDA drug approval documents were reviewed for supportive clinical trial information, and publications were matched using PubMed and Google Scholar searches. Ratios of relative risks (RRR) comparing positive versus non-positive trials before and after FDAAA enactment served to estimate publication bias. We found that the likelihood of publishing positive versus non-positive drug trials in dermatology was unchanged before and after FDAAA enactment (RRR 0.87, 95% CI 0.37–2.08), as was the likelihood of publishing without misleading interpretation (RRR 1.51, 95% CI 0.22–10.50). There was no measurable publication bias for efficacy trials supporting new drug approvals in dermatology over the past 15 years. Fewer pre-FDAAA trials (n = 21) compared to post-FDAAA trials (n = 106) met inclusion criteria. Though not analyzed in this study, safety and secondary efficacy results are other potential sources for publication bias.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

FDAAA:

Food and Drug Administration Amendments Act

FDA:

Food and Drug Administration

NDA:

New drug application

CDER:

Center for Drug Evaluation and Research

CBER:

Center for Biologics Evaluation and Research

INN:

International non-proprietary name

References

  1. Atakpo P, Vassar M (2016) Publication bias in dermatology systematic reviews and meta-analyses. J Dermatol Sci 82:69–74

    Article  PubMed  Google Scholar 

  2. Bieber T, Chosidow O, Bodsworth N, Tyring S, Hercogova J, Bloch M, Davis M, Lewis M, Boutolleau D, Attali P, Group LIPS (2014) Efficacy and safety of aciclovir mucoadhesive buccal tablet in immunocompetent patients with labial herpes (LIP Trial): a double-blind, placebo-controlled, self-initiated trial. J Drugs Dermatol 13:791–798

    CAS  PubMed  Google Scholar 

  3. Center for Biologics Evaluation and Research. https://www.fda.gov/vaccines-blood-biologics. Accessed February 25

  4. Center for Drug Evaluation and Research. https://www.fda.gov/about-fda/office-medical-products-and-tobacco/center-drug-evaluation-and-research. Accessed February 25

  5. Centers for Disease Control and Prevention (CDC). Epi Info for Windows vADoHaHS-C

  6. CenterWatch. FDA Approved Drugs for Dermatology. https://www.centerwatch.com/drug-information/fda-approved-drugs/therapeutic-area/3/dermatology. Accessed February 25

  7. ClinicalTrials.gov. www.clinicaltrials.gov. Accessed March 4

  8. Cook C, Checketts JX, Atakpo P, Nelson N, Vassar M (2018) How well are reporting guidelines and trial registration used by dermatology journals to limit bias? A meta-epidemiological study. Br J Dermatol 178:1433–1434

    Article  CAS  PubMed  Google Scholar 

  9. Crawford JM, Briggs CL, Engeland CG (2010) Publication bias and its implications for evidence-based clinical decision making. J Dent Educ 74:593–600

    Article  PubMed  Google Scholar 

  10. Drugs@FDA: FDA approved drug products. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 25

  11. Drugs@FDA: FDA approved drug products: CDER’s new molecular entities and new therapeutic biological products. https://www.fda.gov/drugs/developmentapprovalprocess/druginnovation/default.html. Accessed March 4

  12. Farquhar CM, Showell MG, Showell EAE, Beetham P, Baak N, Mourad S, Jordan VMB (2017) Clinical trial registration was not an indicator for low risk of bias. J Clin Epidemiol 84:47–53

    Article  PubMed  Google Scholar 

  13. http://www.hutchon.net/CompareRR.htm Cfcterr

  14. https://www.gpo.gov/fdsys/pkg/PLAW-110publ85/html/PLAW-110publ85.htm. Accessed February 25, 2019. FaDAAAFoIEctrdbUSC

  15. Mashayekhi S, Nast A, Gaskins M, Ahmed S, Turner EH, Flohr C (2019) Hidden treasures: exploring selective publication of trials and trial outcomes in biological treatment for plaque psoriasis. Br J Dermatol 181:601–602

    Article  CAS  PubMed  Google Scholar 

  16. Miller JE, Korn D, Ross JS (2015) Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012. BMJ Open 5:e009758

    Article  PubMed  PubMed Central  Google Scholar 

  17. Murad MH, Chu H, Lin L, Wang Z (2018) The effect of publication bias magnitude and direction on the certainty in evidence. BMJ Evid Based Med 23:84–86

    Article  PubMed  PubMed Central  Google Scholar 

  18. Nankervis H, Baibergenova A, Williams HC, Thomas KS (2012) Prospective registration and outcome-reporting bias in randomized controlled trials of eczema treatments: a systematic review. J Invest Dermatol 132:2727–2734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Perlis CS, Harwood M, Perlis RH (2005) Extent and impact of industry sponsorship conflicts of interest in dermatology research. J Am Acad Dermatol 52:967–971

    Article  PubMed  Google Scholar 

  20. Phillips AT, Desai NR, Krumholz HM, Zou CX, Miller JE, Ross JS (2017) Association of the FDA Amendment Act with trial registration, publication, and outcome reporting. Trials 18:333

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rabiya TS (2010) New law may be having some effect on publication bias. JNCI 102(5):290–292. https://doi.org/10.1093/jnci/djq051

    Article  Google Scholar 

  22. Rising K, Bacchetti P, Bero L (2008) Reporting bias in drug trials submitted to the Food and Drug Administration: review of publication and presentation. PLoS Med 5:e217

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sena ES, van der Worp HB, Bath PM, Howells DW, Macleod MR (2010) Publication bias in reports of animal stroke studies leads to major overstatement of efficacy. PLoS Biol 8:e1000344

    Article  PubMed  PubMed Central  Google Scholar 

  24. Tan AC, Jiang I, Askie L, Hunter K, Simes RJ, Seidler AL (2019) Prevalence of trial registration varies by study characteristics and risk of bias. J Clin Epidemiol 113:64–74

    Article  PubMed  Google Scholar 

  25. Zou CX, Becker JE, Phillips AT, Garritano JM, Krumholz HM, Miller JE, Ross JS (2018) Registration, results reporting, and publication bias of clinical trials supporting FDA approval of neuropsychiatric drugs before and after FDAAA: a retrospective cohort study. Trials 19:581

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

SR is supported by the National Institutes of Health 5T32AR007569-24 Grant.

Author information

Authors and Affiliations

  1. Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

    Sairekha Ravichandran, Kathleen M. Mulligan & Harib H. Ezaldein

  2. Northeast Ohio Medical University, Rootstown, OH, USA

    Sairekha Ravichandran

  3. Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jeffrey F. Scott

Authors
  1. Sairekha Ravichandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathleen M. Mulligan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harib H. Ezaldein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffrey F. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Sairekha Ravichandran had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Ezaldein, Ravichandran, and Scott were responsible for study concept and design, acquisition, analysis, and interpretation of data, and drafting of the manuscript. Ravichandran, Mulligan, Ezaldein, and Scott critically revised the manuscript for important intellectual content. Ravichandran carried out statistical analysis. No specific funding was obtained for this research. Ezaldein and Scott were involved in administrative, technical, or material support and study supervision.

Corresponding author

Correspondence to Kathleen M. Mulligan.

Ethics declarations

Conflict of interest

The authors report no conflicts of interest relevant to this work. This work was presented as a poster at the Orlando Dermatology Aesthetic & Clinical Conference in Orlando, Florida, on January 17–20, 2020.

Ethics approval

This study met the definition of Institutional Review Board exempt research.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ravichandran, S., Mulligan, K.M., Ezaldein, H.H. et al. Evaluating publication bias for clinical trials supporting new dermatologic drug approvals from 2003 to 2018. Arch Dermatol Res 315, 831–838 (2023). https://doi.org/10.1007/s00403-022-02449-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-022-02449-6

Keywords

Search

Navigation