title: Effect size comparison of ketorolac nasal spray and commonly prescribed oral combination opioids for pain relief after third molar extraction surgery.
abstract: OBJECTIVE
  Opioids are frequently used for treatment of moderate to severe short-term pain, but concerns exist about this treatment approach. Ketorolac tromethamine nasal spray, a nonsteroidal anti-inflammatory, is indicated for the short-term management of moderate to moderately severe pain requiring analgesia at the opioid level. However, there are no direct comparison studies between ketorolac nasal spray and opioids. The objective of this study was to use an effect size analysis to compare the effectiveness of ketorolac nasal spray with oral combination opioid formulations in treating moderate to severe short-term pain.
  
  
  METHODS
  An effect size analysis of three randomized, double-blind, placebo-controlled studies of third molar extraction surgery compared pain relief with ketorolac nasal spray and commonly prescribed combination opioids including hydrocodone/acetaminophen (APAP), oxycodone/APAP, oxycodone/ibuprofen and tramadol HCl/APAP. Effect size comparisons were made using total pain relief scores (TOTPAR6 or TOTPAR8; the weighted sum of pain relief scores through 6 or 8 h). Pain relief was measured using a five-point categorical rating scale (0 = none; 4 = complete). The effect size equivalent correlation, r, was determined using an online effect size calculator. The treatment effect size r compared with placebo was classified using established criteria (small = 0.20-0.49, moderate = 0.50-0.79 and large = ≥ 0.80).
  
  
  RESULTS
  TOTPAR6 data indicated a moderate effect size for ketorolac nasal spray 31.5 mg (0.51) and oxycodone/ibuprofen 5/400 mg (0.64) and a small effect size for hydrocodone/APAP 7.5/500 mg (0.24) and oxycodone/APAP 5/325 mg (0.32). TOTPAR8 data indicated small effect sizes for ketorolac nasal spray (0.48), hydrocodone/APAP 10/650 mg (0.43), tramadol HCl/APAP 75/650 mg (0.35) and tramadol HCl/APAP 37.5/325 mg (0.17).
  
  
  CONCLUSIONS
  The treatment effect sizes of ketorolac nasal spray were similar to or higher than the opioid comparators after third molar surgery, a well-accepted pain model. These results support ketorolac nasal spray as an effective treatment for moderate to moderately severe short-term pain.
authors.affiliation: a Egalet Corporation , Wayne , PA , USA.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Niebler
authors.affiliation: a Egalet Corporation , Wayne , PA , USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Dayno
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000627:therapeutic use; D007052:Ibuprofen / Q000627:therapeutic use; D020910:Ketorolac / Q000627:therapeutic use*; D008297:Male; D008964:Molar, Third / Q000601:surgery*; D059085:Nasal Sprays; D010098:Oxycodone / Q000627:therapeutic use; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D014081:Tooth Extraction; D014147:Tramadol / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D059085:Nasal Sprays; C083640:acetaminophen, hydrocodone drug combination; C514822:oxycodone-acetaminophen; D000082:Acetaminophen; D014147:Tramadol; D006853:Hydrocodone; D010098:Oxycodone; D007052:Ibuprofen; D020910:Ketorolac
keywords: Combination opioids; effect size; efficacy; ketorolac nasal spray; nonsteroidal anti-inflammatory drug (NSAID); pain