PMID- 33389690 OWN - NLM STAT- MEDLINE DCOM- 20211130 LR - 20240402 IS - 2008-2231 (Electronic) IS - 1560-8115 (Print) IS - 1560-8115 (Linking) VI - 29 IP - 1 DP - 2021 Jun TI - Withdrawal reasons of randomized controlled trials on type 2 diabetes: a systematic review. PG - 39-50 LID - 10.1007/s40199-020-00380-7 [doi] AB - 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 The withdrawal reasons were reported for 91,669 (63.75%) of the total 143,794 participants who had withdrawn from these studies.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. FAU - Mohseni, Shahrzad AU - Mohseni S AUID- ORCID: 0000-0003-3641-0805 AD - Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. AD - Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Tabatabaei-Malazy, Ozra AU - Tabatabaei-Malazy O AUID- ORCID: 0000-0003-0188-9721 AD - Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. tabatabaeiml@sina.tums.ac.ir. FAU - Peimani, Maryam AU - Peimani M AUID- ORCID: 0000-0002-8675-510X AD - Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Ejtahed, Hanieh-Sadat AU - Ejtahed HS AUID- ORCID: 0000-0002-6395-4915 AD - Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. AD - Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Khodaeian, Mehrnoosh AU - Khodaeian M AUID- ORCID: 0000-0001-6064-018X AD - Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Nazeri, Elahe AU - Nazeri E AUID- ORCID: 0000-0003-0956-8375 AD - Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran. FAU - Nouhi, Zahra AU - Nouhi Z AUID- ORCID: 0000-0003-4445-2423 AD - Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Khodamoradi, Kajal AU - Khodamoradi K AUID- ORCID: 0000-0003-2951-4382 AD - Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA. FAU - Aboeerad, Maryam AU - Aboeerad M AUID- ORCID: 0000-0003-0896-6398 AD - Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Larijani, Bagher AU - Larijani B AUID- ORCID: 0000-0001-5386-7597 AD - Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. LA - eng GR - 1396-02-97-2161/Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences/ PT - Journal Article PT - Systematic Review DEP - 20210102 PL - Switzerland TA - Daru JT - Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences JID - 101125969 SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy/psychology MH - Humans MH - Patient Dropouts/*psychology MH - Randomized Controlled Trials as Topic PMC - PMC8149490 OTO - NOTNLM OT - Bias OT - Diabetes mellitus OT - Discontinuing OT - Randomized controlled trials OT - Reasons OT - Systematic review OT - Withdrawal COIS- 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. EDAT- 2021/01/04 06:00 MHDA- 2021/12/01 06:00 PMCR- 2022/01/02 CRDT- 2021/01/03 20:42 PHST- 2020/08/11 00:00 [received] PHST- 2020/12/18 00:00 [accepted] PHST- 2021/01/04 06:00 [pubmed] PHST- 2021/12/01 06:00 [medline] PHST- 2021/01/03 20:42 [entrez] PHST- 2022/01/02 00:00 [pmc-release] AID - 10.1007/s40199-020-00380-7 [pii] AID - 380 [pii] AID - 10.1007/s40199-020-00380-7 [doi] PST - ppublish SO - Daru. 2021 Jun;29(1):39-50. doi: 10.1007/s40199-020-00380-7. Epub 2021 Jan 2.