Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics

Ann Intern Med. 2004 Apr 6;140(7):518-27. doi: 10.7326/0003-4819-140-7-200404060-00011.


Background: A response to proton-pump inhibitors (PPIs) is commonly considered to support the diagnosis of gastroesophageal reflux disease (GERD). However, the accuracy of this diagnostic strategy has not been well established.

Objective: To estimate the diagnostic test characteristics of successful PPI treatment with objective measures of GERD by performing a meta-analysis based on the published literature.

Data sources: English-language studies were identified by searching the Cochrane Clinical Trial Register and MEDLINE from 1 January 1980 through 1 July 2003.

Study selection: Studies in which the clinical response to a short course (1 to 4 weeks) of normal- or high-dose PPI therapy could be compared with objective measures of GERD (24-hour pH monitoring, endoscopy findings, symptom questionnaires).

Data extraction: Studies were screened for inclusion by 1 author. Final decisions on exclusion were made by consensus with 2 of the other authors. Two investigators independently extracted the data. Information extracted included patient characteristics, study design, setting, specific type and dose of medication, duration of treatment, and definitions of outcomes.

Data synthesis: Sensitivity and specificity were determined by comparing a clinical response to PPIs with objective measures for GERD. The summary receiver-operating characteristic curve method was used to summarize test characteristics across studies. Sensitivity and specificity were also combined independently by using a random-effects model. Fifteen studies met the inclusion criteria and provided sufficient data. With 24-hour pH monitoring as the reference standard, the positive likelihood ratio ranged from 1.63 to 1.87, and combined estimates of sensitivity and specificity were 0.78 (95% CI, 0.66 to 0.86) and 0.54 (CI, 0.44 to 0.65), respectively. These values were lower with the other reference standards.

Limitations: Data were insufficient to determine the effect of various doses of PPIs and duration of therapy on test characteristics.

Conclusion: Successful short-term treatment with a PPI in patients suspected of having GERD does not confidently establish the diagnosis when GERD is defined by currently accepted reference standards.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Endoscopy, Gastrointestinal
  • Esophagitis, Peptic / etiology
  • Female
  • Gastroesophageal Reflux / complications
  • Gastroesophageal Reflux / diagnosis*
  • Gastroesophageal Reflux / drug therapy*
  • Heartburn / etiology
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Predictive Value of Tests
  • Proton Pump Inhibitors*
  • ROC Curve


  • Proton Pump Inhibitors