Skip to main content
SpringerLink
Log in

Investigation of the Factors Affecting Risk-Based Quality Management of Investigator-Initiated Investigational New-Drug Trials for Unapproved Anticancer Drugs in Japan

  • Global Perspectives: Original Research
  • Published:
Therapeutic Innovation & Regulatory Science Aims and scope Submit manuscript

Abstract

Background

With an increase in the complexity and cost of clinical trials and the advances in information technology, monitoring guidance issued by regulatory authorities recommends risk-adapted monitoring. To introduce the monitoring method for investigator-initiated investigational new drug (IND) trials using unapproved anticancer drugs, we performed exploratory retrospective analyses to identify risk factors for data quality.

Methods

To select investigator-initiated IND trials using unapproved anticancer drugs, we set the trial selection criteria. Data collection was performed by using audit trails and monitoring reports. Collected data were analyzed by univariate and multivariate analyses to identify the independent risk factors related to error.

Results

By trial selection criteria, 5 investigator-initiated IND trials using unapproved anticancer drugs were selected. The error rates of the total data, critical data, and noncritical data were 7.4%, 9.7%, and 5.9%, respectively. There was no difference between clinical research core hospitals certified by the Ministry of Health, Labour and Welfare and other hospitals in univariate analysis (odds ratio [OR], 1.00; 99% confidence interval [CI], 0.96-1.05; P =.9179). As the main independent risk factors related to error, critical data in the importance of data (OR, 1.28; 99% CI, 1.24-1.33; P <.0001) and groups with ≤3 patients after registration (OR, 1.12; 99% CI, 1.10-1.15; P <.0001) were significantly related to errors in multivariate analysis.

Conclusions

The results of this research suggest that the feasibility of risk-based monitoring and sampling source data verification was indicated for noncritical data and patients after the third case.

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

Similar content being viewed by others

References

  1. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Guidelines for good clinical practices E6(R1). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf. Published 1996. Accessed January 16, 2016.

  2. Smith CT, Stocken DD, Dunn J, et al. The value of source data verification in a cancer clinical trial. PLoS One. 2012;7:e51623.

    Article  CAS  Google Scholar 

  3. Andersen JR, Byrjalsen I, Bihlet A, et al. Impact of source data verification on data quality in clinical trials: an empirical post hoc analysis of three phase 3 randomized clinical trials. Br J Clin Pharmacol. 2015;79:660–668.

    Article  Google Scholar 

  4. Funning S, Grahnén A, Eriksson K, Kettis-Linblad Å. Quality assurance within the scope of good clinical practice (GCP)—what is the cost of GCP-related activities? A survey within the Swedish association of the pharmaceutical industry (LIF)’s members. Qual Assur J. 2009;12:3–7.

    Article  Google Scholar 

  5. Tantsyura V, Grimes I, Mitchel J, et al. Risk-based source data verification approaches: pros and cons. Drug Inf J. 2010;44:745–756.

    Article  Google Scholar 

  6. Tantsyura V, Dunn IM, Waters J, et al. Extended risk-based monitoring model, on-demand query-driven source data verification, and their economic impact on clinical trial operations. Therapeutic Innovation & Regulatory Science. 2016;50:115–122.

    Article  Google Scholar 

  7. Reith C, Landray M, Devereaux PJ, et al. Randomized clinical trials—removing unnecessary obstacles. N Engl J Med. 2013;369:1061–1065.

    Article  CAS  Google Scholar 

  8. US Department of Health and Human Services, Food and Drug Administration. Guidance for industry: oversight of clinical investigations—a risk-based approach to monitoring. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM269919.pdf. Published 2013. Accessed January 16, 2016.

  9. European Medicines Agency. Reflection paper on risk based quality management in clinical trials. EMA/269011/2013. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/11/WC500155491.pdf. Published 2013. Accessed January16, 2016.

  10. Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare. Basic rules of the risk-based approach to monitoring clinical trials. PFSB/ELD notice, 1 July 2013. https://www.pmda.go.jp/files/000161664.pdf. Published 2013. Accessed January 16, 2016.

  11. TransCelerate. Position paper: risk-based monitoring methodology. http://www.transceleratebiopharmainc.com/wp-content/uploads/2016/01/TransCelerate-RBM-Position-Paper-FINAL-30MAY2013.pdf.pdf. Published 2013. Accessed January 23, 2016.

  12. Sheetz N, Wilson B, Benedict J, et al. Evaluating source data verification as a quality control measure in clinical trials. Therapeutic Innovation & Regulatory Science. 2014;48:671–680.

    Article  Google Scholar 

  13. De S. Hybrid approaches to clinical trial monitoring: practical alternatives to 100% source data verification. Perspect Clin Res. 2011;2:100–104.

    Article  Google Scholar 

  14. Nielsen E, Hyder D, Deng C. A data-driven approach to risk-based source data verification. Therapeutic Innovation & Regulatory Science. 2014;48:173–180.

    Article  Google Scholar 

  15. Knepper D, Fenske C, Nadolny P, et al. Detecting data quality issues in clinical trials: current practices and recommendations. Therapeutic Innovation & Regulatory Science. 2016;50:15–21.

    Article  Google Scholar 

  16. Gough J, Wilson B, Zerola M, et al. Defining a central monitoring capability: sharing the experience of TransCelerate BioPharma’s approach, Part 2. Therapeutic Innovation & Regulatory Science. 2015;50:8–14.

    Article  Google Scholar 

  17. Morrison BW, Cochran CJ, White JG, et al. Monitoring the quality of conduct of clinical trials: a survey of current practices. Clin Trials. 2011;8:342–349.

    Article  Google Scholar 

  18. Kurzrock R, Stewart DJ. Compliance in early-phase cancer clinical trials research. Oncologist. 2013;18:308–313.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Research Support, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Tomohisa Sudo MSc & Akihiro Sato MD, PhD

  2. Medical Science Program, Graduate School of Medicine, Keio University, Tokyo, Japan

    Tomohisa Sudo MSc

Authors
  1. Tomohisa Sudo MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akihiro Sato MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tomohisa Sudo MSc.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sudo, T., Sato, A. Investigation of the Factors Affecting Risk-Based Quality Management of Investigator-Initiated Investigational New-Drug Trials for Unapproved Anticancer Drugs in Japan. Ther Innov Regul Sci 51, 589–596 (2017). https://doi.org/10.1177/2168479017705155

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/2168479017705155

Keywords

Search

Navigation