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Withdrawal reasons of randomized controlled trials on type 2 diabetes: a systematic review

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Abstract

Purpose

Type 2 diabetes mellitus (T2DM) is the subject of numerous randomized controlled trials (RCTs). The validity of RCTs may be threatened by attrition bias due to the discontinuation of the study. The aim of this systematic review is to evaluate the reasons of patient’s withdrawal from these RCTs.

Methods

A systematic literature search on PubMed, Cochrane Library, Web of Science, and Scopus databases was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. The aim was to obtain all relevant blinded RCTs published before January 2017 in which the effectiveness of synthetic drugs, vitamins/minerals were compared to that of placebo or active control in T2DM. The quality of RCTs was assessed using the Jadad score. The frequency of withdrawal reasons was presented based on treatments with placebo/active control, national/international level of the studies, and publication year. Meta-analysis was not performed due to the heterogeneity.

Results

Overall, 1368 articles comprising of 640,780 subjects were included. In the majority of the RCTs (75.0%), the intervention and the placebo arms were compared. Most of the included studies (96%) were classified in the high-quality category (Jadad score≥3). The highest proportion of reported withdrawal cases was found in international studies, national RCTs conducted in Japan, and RCTs published in 2011. The withdrawal reasons were reported for 91,669 (63.75%) of the total 143,794 participants who had withdrawn from these studies. The main reported reasons were “adverse effects” (24.04%), “withdraw consent” (16.10%), and “missing data” (11.08%). Variations in the reported withdrawal reasons were based on the country or published year. RCTs with triple blinded design as well as those in which anti-hyperlipidemia and anti-obesity medications were applied, showed significantly higher probability of reported the withdrawal.

Conclusion

High proportion of reported discontinuation in blinded RCTs on patients with T2DM was related to drug adverse effects. Overall, the total number and reason of drop out were unsatisfactory.

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Funding

This study has been supported by “Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences grant numbered 1396-02-97-2161. All of authors thank the Diabetes Research Center for its financial support.

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Authors and Affiliations

  1. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Shahrzad Mohseni & Maryam Peimani

  2. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Shahrzad Mohseni, Hanieh-Sadat Ejtahed, Mehrnoosh Khodaeian, Zahra Nouhi, Maryam Aboeerad & Bagher Larijani

  3. Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Ozra Tabatabaei-Malazy

  4. Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Hanieh-Sadat Ejtahed

  5. Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran

    Elahe Nazeri

  6. Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA

    Kajal Khodamoradi

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  1. Shahrzad Mohseni
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Contributions

SHM did literature bibliography, and drafted some parts of the paper. OTM did literature bibliography, reviewed data, wrote draft and conceived the paper. MP, HSE, MKH, EN, ZN, KKH, MA extracted data, and drafted some parts of the paper. BL conceived, and edited the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ozra Tabatabaei-Malazy.

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All authors declare that there is no conflict of interests. In addition, all authors declare that the supporting fund has not been influenced on submitted manuscript.

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Mohseni, S., Tabatabaei-Malazy, O., Peimani, M. et al. Withdrawal reasons of randomized controlled trials on type 2 diabetes: a systematic review. DARU J Pharm Sci 29, 39–50 (2021). https://doi.org/10.1007/s40199-020-00380-7

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  • DOI: https://doi.org/10.1007/s40199-020-00380-7

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