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Journal of Chinese Integrative Medicine ›› 2006, Vol. 4 ›› Issue (2): 120-129.doi: 10.3736/jcim20060204

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Improving the quality of randomized controlled trials in Chinese herbal medicine, Part Ⅰ: Clinical trial design and methodology

Zhao-xiang Bian1, You-ping Li2, David Moher3, Simon Dagenais3, Liang Liu1, Tai-xiang Wu2, Jiang-xia Miao4, Andrew K.L. Kwan1, Lisa Song1   

  1. 1. School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
    2. Department of Clinical Epidemiology, Chinese Evidence-Based Medicine Centre, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China
    3. Chalmers Research Group, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada
    4. School of Chinese Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
  • Online:2006-03-20 Published:2006-03-15

Objective

To discuss the quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) with respect to design and methodology, and provide suggestions for further improvement in future clinical trials.

Methods

A search of the Cochrane Library was conducted to identify RCTs of CHM on line in July 2005. Quality of the RCTs was assessed using a 11-item checklist modified from the revised CONSORT statement, with 2 items specific to CHM (i.e. herb preparation form and quality control of herbs).

Results

The search yielded 167 RCTs that were selected for assessment. All trials included statements about the interventions, objectives, primary outcome design, statistical methods, and herb preparation form. Although 163 (97.6%) trials reported inclusion criteria, exclusion criteria were only reported in 26 (15.6%) trials. Fewer than 10% of trials clearly stated the random allocation sequence generation methods, and only 2.4% mentioned allocation concealment. The vast majority (86.8%) of trials were open-label, while only 13.2% used blinding. Almost half (45.5%) administered the CHM intervention as a tea or decoction. Only one trial (0.6%) reported a sample size calculation, and a single trial (0.6%) discussed quality control of the CHM intervention.

Conclusion

The overall methodologic quality of RCTs in CHM was poor. It is essential to improve the design of future RCTs in this clinical area. Recommendations: (1) Investigator conducting RCTs should have formal training about clinical trial design; (2) A flow chart is recommended to ensure that all essential steps of clinical trial design are included. (3) Conducting pilot studies prior to RCTs may help improve their design; (4) Registration of clinical trials and publishing their protocols prior to enrolment may reduce publication bias and solicit peer reviews of the proposed design; (5) Collaboration between CHM investigators and traditional medicine academic research centers interested in integrative medicine may lead to quality improvement of RCTs of CHM.

Key words: Randomized controlled trial, Chinese herbal medicine, Methodology, Quality assessment

CLC Number: 

  • R-3

Table 1

Included Cochrane Library systematic reviews about Chinese herbal medicine"

Table 2

Excluded Cochrane Library systematic reviews about Chinese herbal medicine"

Table 3

Checklist of RCTs with Chinese herbal medicine"

Table 4

Basic characteristics of included RCTs"

Figure 1

Flow chart of design of clinical trial"

[1] Moher D, Soeken K, Sampson M , et al. Assessing the quality of reports of systematic reviews in pediatric complementary and alternative medicine[J]. BMC Pediatr, 2002,2(1):3
[2] Linde K, ter Riet G, Hondras M , et al.Systematic reviews of complementary therapies—an annotated bibliography. Part 2: Herbal medicine[J].BMC Complement Altern Med, 2001, 1(): 5
[3] Liu JP, Kjaergard LL, Gluud C . Misuse of randomization: a review of Chinese randomized trials of herbal medicines for chronic hepatitis B[J]. Am J Chin Med, 2002,30(1):173-176
[4] Linde K, Jonas WB, Melchart D , et al. The methodological quality of randomized controlled trials of homeopathy, herbal medicines and acupuncture[J]. Int J Epidemiol, 2001,30(3):526-531
[5] Sackett DL, Straus SE, Richardson WS, et al.Evidence-based medicine: how to practice and teach EBM( 2nd ed) [M].London: Churchill Livingstone , 1997,( 2nd ed):
[6] Schultz KF, Chalmers I, Hayes RJ , et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials[J]. JAMA, 1995,273(5):408-412
[7] Moher D, Pham B, Jones A , et al. Does quality of reports of randomized trials affect estimates of intervention efficacy reported in meta-analyses?[J]. Lancet, 1998,352(9128):609-613
[8] Moher D . CONSORT: an evolving tool to help improve the quality of reports of randomized controlled trials. Consolidated Standards of Reporting Trials[J]. JAMA, 1998,279(18):1489-1491
[9] Moher D, Cook DJ, Jadad AR , et al.Assessing the quality of reports of randomized trials: implications for the conduct of meta-analyses[J].Health Technol Assess, 1999, 3(12):i- iv, 1-98
[10] Altman DG, Schulz KF, Moher D , et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration[J]. Ann Intern Med, 2001,134(8):663-694
pmid: 11304107
[11] Chang ZQ, Chang XY . Clinical observation of integrated traditional Chinese and western medicine in treatment of diabetes[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 1998,18(11):674-676
[12] Schulz KF, Grimes DA . Sample size calculations in randomized trials: mandatory and mystical[J]. Lancet, 2005,365(9467):1348-1353
doi: 10.1016/S0140-6736(05)61034-3 pmid: 15823387
[13] Friedman LM, Furberg CD, DeMets DL.Fundamentals of clinical trials( 3rd ed) [M].New York: Spring Verlag , 1998,( 3rd ed):
[14] Freiman JA, Chalmers TC, Smith H Jr , et al. The importance of beta, the type Ⅱ error and sample size in the design and interpretation of the randomized control trial. Survey of 71 “negative” trials[J]. N Engl J Med, 1978,299(13):690-694
[15] Moher D, Dulberg CS, Wells GA . Statistical power, sample size, and their reporting in randomized controlled trials[J]. JAMA, 1994,272(2):122-124
doi: 10.1097/00008506-199501000-00018 pmid: 8015121
[16] Montenegro R, Needleman I, Moles D , et al. Quality of RCTs in periodontology—a systematic review[J]. J Dent Res, 2002,81(12):866-870
doi: 10.1063/1.1648631 pmid: 12454104
[17] Harrison JE . Clinical trials in orthodontics Ⅱ: assessment of the quality of reporting of clinical trials published in three orthodontic journals between 1989 and 1998[J]. J Orthod, 2003,30(4):309-315
[18] Schulz KF, Grimes DA . Unequal group sizes in randomized trials: guarding against guessing[J]. Lancet, 2002,359(9310):966-970
doi: 10.1016/S0140-6736(02)08029-7 pmid: 11918933
[19] Schulz KF. Grimes DA . Generation of allocation sequences in randomized trials: chance, not choice[J]. Lancet, 2002,359(9305):515-519
doi: 10.1016/S0140-6736(02)07683-3 pmid: 11853818
[20] .[ OTHER].Kjaergard LL, Villumsen J, Gluud C . Quality of randomized clinical trials affects estimates of intervention efficacy. 7th Annual Cochrane Colloquium Abstracts. Rome: 1999.
[21] Juni P, Altman D, Egger M . Systematic review in health care: Assessing the quality of controlled trials[J]. BMJ, 2001,323(7303):42-46
doi: 10.1136/bmj.323.7303.42 pmid: 11440947
[22] Schulz KF, Grimes DA . Allocation concealment in randomized trials: defending against deciphering[J]. Lancet, 2002,359(9306):614-618
doi: 10.1016/S0140-6736(02)07750-4 pmid: 11867132
[23] Schulz KF . Assessing allocation concealment and blinding in randomized controlled trials: Why bother?[J]. ACP J Club, 2000,132(2):A11-A12
doi: 10.2746/042516405774479979 pmid: 10750446
[24] Schulz KF, Grimes DA . Blinding in randomized trials: hiding who got what[J]. Lancet, 2002,359(9307):697-700
doi: 10.1016/S0140-6736(02)07816-9 pmid: 11879884
[25] Kaptchuk TJ . Intentional ignorance: a history of blind assessment and placebo controls in medicine[J]. Bull Hist Med, 1998,72(3):389-433
doi: 10.1353/bhm.1998.0159 pmid: 9780448
[26] Latronico N, Botteri M, Minelli C , et al. Quality of reporting of randomized controlled trials in the intensive care literature. A systematic analysis of papers published in Intensive Care Medicine over 26 years[J]. Intensive Care Med, 2002,28(9):1316-1323
[27] De Angelis, Drazen JM, Frizelle FA , et al. Clinical Trial Registration: A statement from the International Committee of Medical Journal Editors[J]. Croat Med J, 2004,45(5):531-532
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