面对随机对照试验(RCTs)报告质量过低的种种确凿证据和严重后果,许多医学杂志及编辑小组现已接受并支持一份包含有22个条目的清单和一个流程图的CONSORT声明(试验报告统一标准)。由于CONSORT的主旨是提高干预措施疗效的报告质量,故其中只有一个条目是具体针对安全性的。
大量证据表明,报告RCT中的危害的相关数据的报告质量有待提高。2003年5月,CONSORT小组成员,包括杂志编辑和科学家,齐聚加拿大魁北克省Mentoebello探讨了这一问题,并形成以下文件:标准CONSORT清单附带报告危害相关问题的10个新推荐意见,并附上说明及恰当报告的实例。
我们希望该声明连同其它CONSORT相关材料(www.consort-statement.org)将有助于作者提高RCT报告中与危害相关数据的报告质量。高质量报告有助于读者批判性评价和诠释试验结果。各杂志可通过修改稿约来向作者传达这一文件以支持这一目标。
Citation: John P,A,Ioannidis MD,Stephen J,W,Evans MSc,Peter C,Goslash,tzsche MD,DrMedSci,Robert T,ONeill PhD,Douglas G,Altman DSc,Kenneth Schulz PhD,and David Moher PhD,for the CONSORT Group. Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement. Chinese Journal of Evidence-Based Medicine, 2006, 06(9): 682-689. doi: Copy
1. | Cuervo LG, Clarke M. Balancing benefits and harms in health care [Editorial]. BMJ, 2003; 327: 65–66. |
2. | Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med, 2001; 134: 663–694. |
3. | Moher D, Schulz KF, Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA, 2001; 285: 1987–1991. |
4. | Stephens MD, Talbot JC, Routledge PA, eds. The Detection of New Adverse Reactions. 4th ed. London: Macmillan Reference; 1998. |
5. | Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet, 2000; 356: 1255–1259. |
6. | Ioannidis JP, Contopoulos-Ioannidis DG. Reporting of safety data from randomized trials [Letter]. Lancet, 1998; 352: 1752–1753. |
7. | Ioannidis JP, Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. JAMA, 2001; 285: 437–443. |
8. | Gøtzsche PC. Methodology and overt and hidden bias in reports of 196 double-blind trials of nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Control Clin Trials, 1989; 10: 31-56. |
9. | Loke YK, Derry S. Reporting of adverse drug reactions in randomised controlled trials—a systematic survey. BMC Clin Pharmacol, 2001; 1: 3. |
10. | Edwards JE, McQuay HJ, Moore RA, et al. Reporting of adverse effects in clinical trials should be improved: lessons from acute postoperative pain. J Pain Symptom Manage, 1999; 18: 427–437. |
11. | Hayashi K, Walker AM. Japanese and American reports of randomized trials: differences in the reporting of adverse effects. Control Clin Trials, 1996; 17: 99–110. |
12. | Papanikolaou PN, Churchill R, Wahlbeck K, et al. Safety reporting in randomized trials of mental health interventions. Am J Psychiatry, 2004; 161: 1692–1697. |
13. | Martin RC 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg, 2002; 235: 803–813. |
14. | Ioannidis JP, Chew P, Lau J. Standardized retrieval of side effects data for meta-analysis of safety outcomes. A feasibility study in acute sinusitis. J Clin Epidemiol, 2002; 55: 619–626. |
15. | Ioannidis JP, Lau J. Improving safety reporting from randomised trials. Drug Saf, 2002; 25: 77–84. |
16. | Mucklow JC. Reporting drug safety in clinical trials: getting the emphasis right. Lancet, 2001; 357: 1384. |
17. | Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. JAMA, 1995; 273: 929–933. |
18. | Castle W, Fuller R, Hall J, et al. Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ, 1993; 306: 1034–1037. |
19. | Derry S, Kong Loke Y, Aronson JK. Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials. BMC Med Res Methodol, 2001; 1: 7. |
20. | Myers MG, Cairns JA, Singer J. The consent form as a possible cause of side effects. Clin Pharmacol Ther, 1987; 42: 250–253. |
21. | Rochon PA, Binns MA, Litner JA, et al. Are randomized control trial outcomes influenced by the inclusion of a placebo group? A systematic review of nonsteroidal antiinflammatory drug trials for arthritis treatment. J Clin Epidemiol, 1999; 52: 113–122. |
22. | Peloso PM, Wright JG, Bombardier C. A critical appraisal of toxicity indexes in rheumatology. J Rheumatol, 1995; 22: 989–994. |
23. | Marshall M, Lockwood A, Bradley C, et al. Unpublished rating scales: a major source of bias in randomised controlled trials of reatments for schizophrenia. Br J Psychiatry, 2000; 176: 249–252. |
24. | Vitiello B, Riddle MA, Greenhill LL, et al. How can we improve the assessment of safety in child and adolescent psychopharmacology? J Am Acad Child Adolesc Psychiatry, 2003; 42: 634–641. |
25. | Bonhoeffer J, Kohl K, Chen R, et al. The Brighton Collaboration: addressing the need for standardized case definitions of adverse events following immunization (AEFI). Vaccine, 2002; 21: 298–302. |
26. | Woodworth TG, Furst DE, Strand V, et al. Standardizing assessment of adverse effects in rheumatology clinical trials. Status of OMERACT Toxicity Working Group March 2000: towards a common understanding of comparative toxicity/safety profiles for antirheumatic therapies. J Rheumatol, 2001; 28: 1163–1169. |
27. | Trotti A, Bentzen SM. The need for adverse effects reporting standards in oncology clinical trials [Editorial]. J Clin Oncol, 2004; 22: 19–22. |
28. | Kohl KS, Bonhoeffer J, Chen R, et al. The Brighton Collaboration: enhancing comparability of vaccine safety data. Pharmacoepidemiol Drug Saf, 2003; 12: 335–340. |
29. | Division of AIDS. Table for Grading Severity of Adult Adverse Experiences. Rockville, MD: National Institute of Allergy and Infectious Diseases; 1992. |
30. | Miller AB, Hoogstraten B, Staquet M, et al. Reporting results of cancer treatment. Cancer, 1981; 47: 207–214. |
31. | Common Toxicity Criteria, version 2. Bethesda, MD: National Cancer Institute; 1999. |
32. | Corso DM, Pucino F, DeLeo JM, et al. Development of a questionnaire for detecting potential adverse drug reactions. Ann Pharmacother, 1992; 26: 890–896. |
33. | Wallin J, Sjovall J. Detection of adverse drug reactions in a clinical trial using two types of questioning. Clin Ther, 1981; 3: 450–452. |
34. | Gøtzsche PC. Non-steroidal anti-inflammatory drugs. BMJ, 2000; 320: 1058–1061. |
35. | Roehrborn CG. Reporting of acute urinary retention in BPH treatment trials: importance of patient follow-up after discontinuation and case definitions. Urology, 2002; 59: 811–815. |
36. | Wahlbeck K, Tuunainen A, Ahokas A, et al. Dropout rates in randomized antipsychotic drug trials. Psychopharmacology (Berl), 2001; 155: 230–233. |
37. | Whitehead J. On being the statistician on a Data and Safety Monitoring Board. Stat Med, 1999; 18: 3425–3434. |
38. | Thall PF, Cheng SC. Optimal two-stage designs for clinical trials based on safety and efficacy. Stat Med, 2001; 20: 1023–1032. |
39. | Sanders C, Egger M, Donovan J, et al. Reporting on quality of life in randomised controlled trials: bibliographic study. BMJ, 1998; 317: 1191–1194. |
40. | Smith A. Report of the Statisticians in the Pharmaceutical Industry Working Party, 1980. |
41. | Chuang-Stein C. Laboratory data in clinical trials: a statistician’s perspective. Control Clin Trials, 1998; 19: 167–177. |
42. | Cato A. Premarketing adverse drug experiences: data management procedures. Unexpected death occurring early in clinical trials. Drug Inf J, 1987; 21: 3–7. |
43. | Chan AW, Hro´bjartsson A, Haahr MT, et al. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA, 2004; 291: 2457–2465. |
44. | Jovanovic BD, Zalenski RJ. Safety evaluation and confidence intervals when the number of observed events is small or zero. Ann Emerg Med, 1997; 30:301–306. |
45. | Oxman AD, Guyatt GH. A consumer’s guide to subgroup analyses. Ann Intern Med, 1992; 116: 78–84. |
46. | Yusuf S, Wittes J, Probstfield J, et al. Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. JAMA, 1991; 266: 93–98. |
47. | Clarke M, Alderson P, Chalmers I. Discussion sections in reports of controlled trials published in general medical journals. JAMA, 2002; 287: 2799–2801. |
48. | Docherty M, Smith R. The case for structuring the discussion of scientific papers [Editorial]. BMJ, 1999; 318: 1224–1225. |
49. | O’Neill RT. Regulatory perspectives on data monitoring. Stat Med, 2002; 21: 2831–2842. |
- 1. Cuervo LG, Clarke M. Balancing benefits and harms in health care [Editorial]. BMJ, 2003; 327: 65–66.
- 2. Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med, 2001; 134: 663–694.
- 3. Moher D, Schulz KF, Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA, 2001; 285: 1987–1991.
- 4. Stephens MD, Talbot JC, Routledge PA, eds. The Detection of New Adverse Reactions. 4th ed. London: Macmillan Reference; 1998.
- 5. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet, 2000; 356: 1255–1259.
- 6. Ioannidis JP, Contopoulos-Ioannidis DG. Reporting of safety data from randomized trials [Letter]. Lancet, 1998; 352: 1752–1753.
- 7. Ioannidis JP, Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. JAMA, 2001; 285: 437–443.
- 8. Gøtzsche PC. Methodology and overt and hidden bias in reports of 196 double-blind trials of nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Control Clin Trials, 1989; 10: 31-56.
- 9. Loke YK, Derry S. Reporting of adverse drug reactions in randomised controlled trials—a systematic survey. BMC Clin Pharmacol, 2001; 1: 3.
- 10. Edwards JE, McQuay HJ, Moore RA, et al. Reporting of adverse effects in clinical trials should be improved: lessons from acute postoperative pain. J Pain Symptom Manage, 1999; 18: 427–437.
- 11. Hayashi K, Walker AM. Japanese and American reports of randomized trials: differences in the reporting of adverse effects. Control Clin Trials, 1996; 17: 99–110.
- 12. Papanikolaou PN, Churchill R, Wahlbeck K, et al. Safety reporting in randomized trials of mental health interventions. Am J Psychiatry, 2004; 161: 1692–1697.
- 13. Martin RC 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg, 2002; 235: 803–813.
- 14. Ioannidis JP, Chew P, Lau J. Standardized retrieval of side effects data for meta-analysis of safety outcomes. A feasibility study in acute sinusitis. J Clin Epidemiol, 2002; 55: 619–626.
- 15. Ioannidis JP, Lau J. Improving safety reporting from randomised trials. Drug Saf, 2002; 25: 77–84.
- 16. Mucklow JC. Reporting drug safety in clinical trials: getting the emphasis right. Lancet, 2001; 357: 1384.
- 17. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. JAMA, 1995; 273: 929–933.
- 18. Castle W, Fuller R, Hall J, et al. Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ, 1993; 306: 1034–1037.
- 19. Derry S, Kong Loke Y, Aronson JK. Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials. BMC Med Res Methodol, 2001; 1: 7.
- 20. Myers MG, Cairns JA, Singer J. The consent form as a possible cause of side effects. Clin Pharmacol Ther, 1987; 42: 250–253.
- 21. Rochon PA, Binns MA, Litner JA, et al. Are randomized control trial outcomes influenced by the inclusion of a placebo group? A systematic review of nonsteroidal antiinflammatory drug trials for arthritis treatment. J Clin Epidemiol, 1999; 52: 113–122.
- 22. Peloso PM, Wright JG, Bombardier C. A critical appraisal of toxicity indexes in rheumatology. J Rheumatol, 1995; 22: 989–994.
- 23. Marshall M, Lockwood A, Bradley C, et al. Unpublished rating scales: a major source of bias in randomised controlled trials of reatments for schizophrenia. Br J Psychiatry, 2000; 176: 249–252.
- 24. Vitiello B, Riddle MA, Greenhill LL, et al. How can we improve the assessment of safety in child and adolescent psychopharmacology? J Am Acad Child Adolesc Psychiatry, 2003; 42: 634–641.
- 25. Bonhoeffer J, Kohl K, Chen R, et al. The Brighton Collaboration: addressing the need for standardized case definitions of adverse events following immunization (AEFI). Vaccine, 2002; 21: 298–302.
- 26. Woodworth TG, Furst DE, Strand V, et al. Standardizing assessment of adverse effects in rheumatology clinical trials. Status of OMERACT Toxicity Working Group March 2000: towards a common understanding of comparative toxicity/safety profiles for antirheumatic therapies. J Rheumatol, 2001; 28: 1163–1169.
- 27. Trotti A, Bentzen SM. The need for adverse effects reporting standards in oncology clinical trials [Editorial]. J Clin Oncol, 2004; 22: 19–22.
- 28. Kohl KS, Bonhoeffer J, Chen R, et al. The Brighton Collaboration: enhancing comparability of vaccine safety data. Pharmacoepidemiol Drug Saf, 2003; 12: 335–340.
- 29. Division of AIDS. Table for Grading Severity of Adult Adverse Experiences. Rockville, MD: National Institute of Allergy and Infectious Diseases; 1992.
- 30. Miller AB, Hoogstraten B, Staquet M, et al. Reporting results of cancer treatment. Cancer, 1981; 47: 207–214.
- 31. Common Toxicity Criteria, version 2. Bethesda, MD: National Cancer Institute; 1999.
- 32. Corso DM, Pucino F, DeLeo JM, et al. Development of a questionnaire for detecting potential adverse drug reactions. Ann Pharmacother, 1992; 26: 890–896.
- 33. Wallin J, Sjovall J. Detection of adverse drug reactions in a clinical trial using two types of questioning. Clin Ther, 1981; 3: 450–452.
- 34. Gøtzsche PC. Non-steroidal anti-inflammatory drugs. BMJ, 2000; 320: 1058–1061.
- 35. Roehrborn CG. Reporting of acute urinary retention in BPH treatment trials: importance of patient follow-up after discontinuation and case definitions. Urology, 2002; 59: 811–815.
- 36. Wahlbeck K, Tuunainen A, Ahokas A, et al. Dropout rates in randomized antipsychotic drug trials. Psychopharmacology (Berl), 2001; 155: 230–233.
- 37. Whitehead J. On being the statistician on a Data and Safety Monitoring Board. Stat Med, 1999; 18: 3425–3434.
- 38. Thall PF, Cheng SC. Optimal two-stage designs for clinical trials based on safety and efficacy. Stat Med, 2001; 20: 1023–1032.
- 39. Sanders C, Egger M, Donovan J, et al. Reporting on quality of life in randomised controlled trials: bibliographic study. BMJ, 1998; 317: 1191–1194.
- 40. Smith A. Report of the Statisticians in the Pharmaceutical Industry Working Party, 1980.
- 41. Chuang-Stein C. Laboratory data in clinical trials: a statistician’s perspective. Control Clin Trials, 1998; 19: 167–177.
- 42. Cato A. Premarketing adverse drug experiences: data management procedures. Unexpected death occurring early in clinical trials. Drug Inf J, 1987; 21: 3–7.
- 43. Chan AW, Hro´bjartsson A, Haahr MT, et al. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA, 2004; 291: 2457–2465.
- 44. Jovanovic BD, Zalenski RJ. Safety evaluation and confidence intervals when the number of observed events is small or zero. Ann Emerg Med, 1997; 30:301–306.
- 45. Oxman AD, Guyatt GH. A consumer’s guide to subgroup analyses. Ann Intern Med, 1992; 116: 78–84.
- 46. Yusuf S, Wittes J, Probstfield J, et al. Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. JAMA, 1991; 266: 93–98.
- 47. Clarke M, Alderson P, Chalmers I. Discussion sections in reports of controlled trials published in general medical journals. JAMA, 2002; 287: 2799–2801.
- 48. Docherty M, Smith R. The case for structuring the discussion of scientific papers [Editorial]. BMJ, 1999; 318: 1224–1225.
- 49. O’Neill RT. Regulatory perspectives on data monitoring. Stat Med, 2002; 21: 2831–2842.