Evidence-Based Reviews

Dissecting clinical trials with ‘number needed to treat’

Current Psychiatry. 2007 March;6(3):66-71

References

1. Gray GE, Pinson LA. Evidence-based medicine and psychiatric practice. Psychiatr Q 2003;74(4):387-99.

2. Guyatt GH, Rennie D. Users’ guides to the medical literature [editorial]. JAMA 1993;270(17):2096-7.

3. Citrome L, Stroup TS. Schizophrenia, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and number needed to treat: how can CATIE inform clinicians? Int J Clin Pract 2006;60(8):933-40.

4. Leslie DL, Rosenheck RA. Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications. Am J Psychiatry 2004;161(9):1709-11.

5. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353(12):1209-23.

6. McEvoy JP, Lieberman JA, Stroup TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006;163(4):600-10.

7. Stroup TS, Lieberman JA, McEvoy JP, et al. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatry 2006;163(4):611-22.

8. Carey B. Little difference found in schizophrenia drugs. The New York Times. September 20, 2005.

9. Essock SM, Covell NH, Davis SM, et al. Effectiveness of switching antipsychotic medications. Am J Psychiatry 2006;163(12):2090-5.

10. Citrome L, Volavka J. Optimal dosing of atypical antipsychotics in adults: a review of the current evidence. Harv Rev Psychiatry 2002;10(5):280-91.

Potential pitfalls

Different studies can provide different estimates of outcomes such as response, remission, hospitalization, or adverse events. Two studies of the risk of new-onset diabetes with antipsychotics demonstrate that these differences can be difficult to interpret, particularly when populations and study designs differ.

A Department of Veterans Affairs study of data on 56,849 patients⁴ produced an NNH of 159 when olanzapine was compared with conventional antipsychotics, meaning 1 extra case of new-onset diabetes was encountered for every 159 patients treated with olanzapine compared to conventional antipsychotics.
In the CATIE study,⁵ examining new prescriptions of antidiabetic agents yields an NNH of 61 when olanzapine is compared with perphenazine, meaning that 1 extra case of a new prescription of an antidiabetic agent was encountered for every 61 patients treated with olanzapine versus perphenazine.

A statistically significant NNT or NNH should carry more weight than a result that is not statistically significant. Even so, make sure the study included patients similar to individuals in your practice before applying the results.

NNT and NNH are best calculated from well-controlled clinical trials. However, the underlying study design and potential biases may affect how NNT and NNH apply to clinical practice. A more complete discussion of the CATIE NNT and NNH secondary analysis can be found elsewhere,³ but issues to consider include the impact of differential switching⁹ and the possible effects of dosages.¹⁰

Related resources

Guyatt G, Rennie D. Users’ guides to the medical literature: a manual for evidence-based clinical practice. Chicago: AMA Press; 2001.
Straus SE, Richardson WS, Glasziou P, et al. Evidence-based medicine: how to practice and teach EBM, 3rd ed. Edinburgh, UK: Elsevier/Churchill Livingstone; 2005.

Drug brand names

Clozapine • Clozaril
Olanzapine • Zyprexa
Perphenazine • Trilafon
Quetiapine • Seroquel
Risperidone • Risperdal
Ziprasidone • Geodon

Disclosure

Dr. Citrome receives research support from AstraZeneca Pharmaceuticals, Barr Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly and Company, Forest Pharmaceuticals, Janssen Pharmaceutica, and Pfizer. He is a consultant to Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Jazz Pharmaceuticals, and Pfizer, and a speaker for Abbott Laboratories, AstraZeneca Pharmaceuticals, Eli Lilly and Company, and Pfizer.

Dissecting clinical trials with ‘number needed to treat’

References

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