This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (127)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in JAMA  Topic Collections  • Patient Safety/ Medical Error  • Gastrointestinal Diseases  • HIV/AIDS  • Randomized Controlled Trial  • Otolaryngology/ Head & Neck Surgery  • General Rhinology  • Cardiovascular Disease/ Myocardial Infarction  • Cardiovascular Intervention  • Thrombolysis  • Adverse Effects  • Alert me on articles by topic

An Evaluation of 7 Medical Areas

John P. A. Ioannidis, MD; Joseph Lau, MD

JAMA. 2001;285:437-443.

Context  Randomized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting; however, generalizable data on drug safety reporting are sparse.

Objective  To scrutinize the completeness of safety reporting in randomized trials.

Design, Setting, and Patients  Survey of safety reporting in 192 randomized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm (N = 130074 patients). Trial reports were identified from comprehensive meta-analyses in 7 medical areas.

Main Outcome Measures  Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects; article space allocated to safety reporting and predictors of such reporting.

Results  Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39% and 29% of trial reports, respectively. Only 46% of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity. For these 3 parameters, there was significant heterogeneity in rates of adequate reporting across topics (P = .003, P<.001, and P = .02, respectively). Overall, the median space allocated to safety results was 0.3 page. A similar amount of space was devoted to contributor names and affiliations (P = .16). On average, the percentage of space devoted to safety in the results section was 9.3% larger in trials involving dose comparisons than in those that did not (P<.001) and 3.8% smaller in trials reporting statistically significant results for efficacy outcomes (P = .047).

Conclusions  The quality and quantity of safety reporting vary across medical areas, study designs, and settings but they are largely inadequate. Current standards for safety reporting in randomized trials should be revised to address this inadequacy.

Author Affiliations: Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece (Dr Ioannidis); and Division of Clinical Care Research, Department of Medicine, New England Medical Center, Boston, Mass (Drs Ioannidis and Lau).

RELATED ARTICLES

Safety Outcomes in Meta-analyses of Phase 2 vs Phase 3 Randomized Trials: Intracranial Hemorrhage in Trials of Bolus Thrombolytic Therapy
John W. Eikelboom, Shamir R. Mehta, Janice Pogue, and Salim Yusuf
JAMA. 2001;285(4):444-450.
ABSTRACT | FULL TEXT  

January 24/31, 2001
JAMA. 2001;285(4):475-476.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

What is "quality of evidence" and why is it important to clinicians?
Guyatt et al.
BMJ 2008;336:995-998.
FULL TEXT  

Treatment for Lymphatic Filariasis and Elephantiasis--Reply
Reddy et al.
JAMA 2008;299:633-633.
FULL TEXT  

Meta-analysis: Effect of Monotherapy and Combination Therapy with Inhibitors of the Renin Angiotensin System on Proteinuria in Renal Disease
Kunz et al.
ANN INTERN MED 2008;148:30-48.
ABSTRACT | FULL TEXT  

Patient-Reported Outcomes and the Evolution of Adverse Event Reporting in Oncology
Trotti et al.
JCO 2007;25:5121-5127.
ABSTRACT | FULL TEXT  

Oral Drug Therapy for Multiple Neglected Tropical Diseases: A Systematic Review
Reddy et al.
JAMA 2007;298:1911-1924.
ABSTRACT | FULL TEXT  

Systematic review of the clinical efficacy and safety of sevelamer in dialysis patients
Tonelli et al.
Nephrol Dial Transplant 2007;22:2856-2866.
ABSTRACT | FULL TEXT  

Placebo-controlled trials of Chinese herbal medicine and conventional medicine comparative study
Shang et al.
Int J Epidemiol 2007;36:1086-1092.
ABSTRACT | FULL TEXT  

Evaluation of Early and Late Toxicities in Chemoradiation Trials
Bentzen and Trotti
JCO 2007;25:4096-4103.
ABSTRACT | FULL TEXT  

Systematic Reviews: Time to Address Clinical and Policy Relevance As Well As Methodological Rigor
Laupacis and Straus
ANN INTERN MED 2007;147:273-274.
FULL TEXT  

Measurement of long-term outcomes in observational and randomised controlled trials
Hodgson et al.
Br. J. Psychiatry 2007;191:s78-s84.
ABSTRACT | FULL TEXT  

Stopping at Nothing? Some Dilemmas of Data Monitoring in Clinical Trials
Goodman
ANN INTERN MED 2007;146:882-887.
ABSTRACT | FULL TEXT  

A survey of inclusion of the time element when reporting adverse effects in randomised controlled trials of cyclo-oxygenase-2 and tumour necrosis factor {alpha} inhibitors
Yazici and Yazici
Ann Rheum Dis 2007;66:124-127.
ABSTRACT | FULL TEXT  

Adverse Events Associated With Pediatric Spinal Manipulation: A Systematic Review
Vohra et al.
Pediatrics 2007;119:e275-e283.
ABSTRACT | FULL TEXT  

Documenting research in scientific articles: guidelines for authors: reporting research designs and activities.
Lang
Chest 2006;130:1263-1268.
FULL TEXT  

An educational intervention to improve physician reporting of adverse drug reactions: a cluster-randomized controlled trial.
Figueiras et al.
JAMA 2006;296:1086-1093.
ABSTRACT | FULL TEXT  

On the Toxicity of Chemotherapy for Breast Cancer--the Need for Vigilance.
Erban and Lau
JNCI J Natl Cancer Inst 2006;98:1096-1097.
FULL TEXT  

Frequency and cost of chemotherapy-related serious adverse effects in a population sample of women with breast cancer.
Hassett et al.
JNCI J Natl Cancer Inst 2006;98:1108-1117.
ABSTRACT | FULL TEXT  

Denosumab in postmenopausal women with low bone mineral density.
Schwartzman et al.
NEJM 2006;354:2390-2391.
FULL TEXT  

Systematic review and meta-analysis of ethnic differences in risks of adverse reactions to drugs used in cardiovascular medicine
McDowell et al.
BMJ 2006;332:1177-1181.
ABSTRACT | FULL TEXT  

Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies
Papanikolaou et al.
CMAJ 2006;174:635-641.
ABSTRACT | FULL TEXT  

Adverse events: the more you search, the more you find.
Ioannidis et al.
ANN INTERN MED 2006;144:298-300.
FULL TEXT  

Does melatonin help people sleep?
Herxheimer
BMJ 2006;332:373-374.
FULL TEXT  

Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis
Lee et al.
BMJ 2006;332:328-336.
ABSTRACT | FULL TEXT  

Dealing With a Deluge of Data: An Assessment of Adverse Event Data on North Central Cancer Treatment Group Trials
Mahoney et al.
JCO 2005;23:9275-9281.
ABSTRACT | FULL TEXT  

Effects of Adding Ribavirin to Interferon to Treat Chronic Hepatitis C Infection: A Systematic Review and Meta-analysis of Randomized Trials
Brok et al.
Arch Intern Med 2005;165:2206-2212.
ABSTRACT | FULL TEXT  

Reporting of Harm in Randomized, Controlled Trials of Nonpharmacologic Treatment for Rheumatic Disease
Ethgen et al.
ANN INTERN MED 2005;143:20-25.
ABSTRACT | FULL TEXT  

Challenges in Systematic Reviews That Assess Treatment Harms
Chou and Helfand
ANN INTERN MED 2005;142:1090-1099.
ABSTRACT | FULL TEXT  

Challenges in Systematic Reviews of Therapeutic Devices and Procedures
Hartling et al.
ANN INTERN MED 2005;142:1100-1111.
ABSTRACT | FULL TEXT  

Expectant, Medical, or Surgical Management of First-Trimester Miscarriage: A Meta-Analysis
Sotiriadis et al.
Obstet Gynecol 2005;105:1104-1113.
ABSTRACT | FULL TEXT  

A Prescribing Cascade Involving Cholinesterase Inhibitors and Anticholinergic Drugs
Gill et al.
Arch Intern Med 2005;165:808-813.
ABSTRACT | FULL TEXT  

Extended-Interval Aminoglycosides in Children: More Guidance Is Needed
Best et al.
Pediatrics 2005;115:827-828.
FULL TEXT  

Potential Pitfalls of Disease-Specific Guidelines for Patients with Multiple Conditions
Tinetti et al.
NEJM 2004;351:2870-2874.
FULL TEXT  

Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement
Ioannidis et al.
ANN INTERN MED 2004;141:781-788.
ABSTRACT | FULL TEXT  

Safety Reporting in Randomized Trials of Mental Health Interventions
Papanikolaou et al.
Am. J. Psychiatry 2004;161:1692-1697.
ABSTRACT | FULL TEXT  

Opportunities and challenges for improving the quality of reporting clinical research: CONSORT and beyond
Moher et al.
CMAJ 2004;171:349-350.
FULL TEXT  

Open access to industry's clinically relevant data
Herxheimer
BMJ 2004;329:64-65.
FULL TEXT  

Evidence Report on the Treatment of Pain in Cancer Patients
Carr et al.
J Natl Cancer Inst Monogr 2004;2004:23-31.
ABSTRACT | FULL TEXT  

Antidepressants and adverse effects in young patients: uncovering the evidence
Herxheimer and Mintzes
CMAJ 2004;170:487-489.
FULL TEXT  

The Need for Adverse Effects Reporting Standards in Oncology Clinical Trials
Trotti and Bentzen
JCO 2004;22:19-22.
FULL TEXT  

Informed Consent And The Psychiatric Drugging Of Children
Breeding and Baughman
Journal of Humanistic Psychology 2003;43:50-64.
ABSTRACT  

The STARD Statement for Reporting Studies of Diagnostic Accuracy: Explanation and Elaboration
Bossuyt et al.
ANN INTERN MED 2003;138:W1-W12.
ABSTRACT | FULL TEXT  

The STARD Statement for Reporting Studies of Diagnostic Accuracy: Explanation and Elaboration
Bossuyt et al.
Clin. Chem. 2003;49:7-18.
ABSTRACT | FULL TEXT  

Population-Based Assessment of Hospitalizations for Toxicity From Chemotherapy in Older Women With Breast Cancer
Du et al.
JCO 2002;20:4636-4642.
ABSTRACT | FULL TEXT  

Risk of myelotoxicity with intravenous cyclophosphamide in patients with systemic lupus erythematosus
Katsifis et al.
Rheumatology (Oxford) 2002;41:780-786.
ABSTRACT | FULL TEXT  

Survey of Modalities of Toxicity Assessment and Reporting in Noncomparative Prospective Studies of Chemotherapy in Breast Cancer
Perrone et al.
JCO 2002;20:52-57.
ABSTRACT | FULL TEXT  

Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for upper respiratory tract infections
Ioannidis et al.
J Antimicrob Chemother 2001;48:677-689.
ABSTRACT | FULL TEXT  

Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for lower respiratory tract infections
Contopoulos-Ioannidis et al.
J Antimicrob Chemother 2001;48:691-703.
ABSTRACT | FULL TEXT  

How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis
Schachter et al.
CMAJ 2001;165:1475-1488.
ABSTRACT | FULL TEXT  

Safety Reporting in Clinical Trials
Calis et al.
JAMA 2001;285:2076-2078.
FULL TEXT