***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract  Variability  in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Anti-inflammatory drugs should impair wound healing , which may explain why they have been used to only a limited extent to relieve pain . If they are to have maximal effect they must be started before the operation . In the present study , single doses of the non-steroidal anti-inflammatory agent diclofenac or of diclofenac and the corticosteroid methylprednisolone were given before operation , and the effects on wound healing after operative extraction of third molars were recorded . Patients developed 18 postoperative complications ( 5 % ) , the most common of which was alveolar osteitis ( n = 14 ) , followed by bleeding ( n = 3 ) and infection ( n = 1 ) . Pretreatment with diclofenac alone or in combination with methylprednisolone did not result in a notable increase in the incidence of complications as compared to placebo BACKGROUND Rofecoxib is a selective cyclooxygenase-2 inhibitor indicated for the treatment of acute pain , with similar analgesic efficacy to ibuprofen and naproxen sodium . Diclofenac sodium is the most commonly prescribed nonsteroidal anti-inflammatory drug worldwide ; it is effective for the treatment of pain as well as the signs and symptoms associated with the painful conditions of osteoarthritis and rheumatoid arthritis . OBJECTIVE The aim of this study was to compare the analgesic efficacy and tolerability of a single dose of rofecoxib 50 mg , 3 doses of enteric-coated diclofenac sodium 50 mg , and placebo over 8-hour and 24-hour periods in patients with moderate to severe pain after oral surgery . METHODS In this double-blind , placebo- and active comparator-controlled , parallel-group study , patients experiencing moderate to severe pain after the surgical extraction of > or = 2 third molars were r and omized to receive a single dose of rofecoxib 50 mg , 3 doses of enteric-coated diclofenac sodium 50 mg ( 50 mg given every 8 hours ) , or placebo . Patients rated pain intensity , pain relief , and global assessment s at prespecified times throughout the 24-hour period after initial dosing . Overall analgesic efficacy was determined by total pain relief over 8 hours ( TOPAR8 ) and 24 hours ( TOPAR24 ) and patient global assessment s at 8 and 24 hours . Onset of analgesic effect was determined by using the 2-stopwatch method for confirmed perceptible pain relief . Peak analgesic effect was the maximum pain relief attained during the first 8 hours . The duration of analgesic effect was determined by median time to rescue analgesia use . RESULTS A total of 305 patients were r and omized to treatment : 121 received rofecoxib , 121 received diclofenac sodium , and 63 received placebo . The baseline demographics were similar among the groups . Overall , 61.3 % experienced moderate pain and 38.7 % experienced severe pain ; 53.1 % were female ; and the mean age was 23.4 years . The overall analgesic efficacy , as assessed by TOPAR8 , of a single dose of rofecoxib 50 mg was significantly greater than a single dose of enteric-coated diclofenac sodium 50 mg ( 20.5 vs 8.2 ) and placebo ( 20.5 vs 5.9 ) . Patient global assessment at 8 hours was also significantly better for rofecoxib compared with enteric-coated diclofenac sodium and placebo . TOPAR24 was significantly greater for a single dose of rofecoxib 50 mg compared with 3 doses of enteric-coated diclofenac sodium 50 mg ( 64.1 vs 25.1 ) and placebo ( 64.1 vs 19.2 ) . At 24 hours , the patient global assessment for rofecoxib was significantly better than that achieved with enteric-coated diclofenac sodium and placebo . The onset of analgesic effect was significantly more rapid for rofecoxib than for enteric-coated diclofenac sodium and placebo ( median times : 31 minutes , > 4 hours , and > 4 hours , respectively ) . The peak analgesic effect was significantly greater for rofecoxib compared with enteric-coated diclofenac sodium ( 3.2 vs 1.5 ) and placebo ( 3.2 vs 1.1 ) . The duration of analgesia was significantly longer for rofecoxib than enteric-coated diclofenac sodium ( median times : > 24 hours vs 1 hour and 37 minutes ) and placebo ( > 24 hours vs 1 hour and 37 minutes ) . Enteric-coated diclofenac sodium was numerically greater than placebo for the key end points measuring overall efficacy ( total pain relief and patient global assessment ) , but diclofenac sodium did not provide as much analgesic effect as expected for a drug effective for pain , osteoarthritis , and rheumatoid arthritis and did not differ significantly from placebo . Overall , both rofecoxib and enteric-coated diclofenac sodium were generally well tolerated , although the rofecoxib group had a significantly lower incidence of clinical and drug-related adverse events than the enteric-coated diclofenac sodium group . CONCLUSIONS A single 50-mg dose of rofecoxib provided greater overall analgesic efficacy over 8 hours , more rapid onset of analgesia , greater maximum analgesic effect , and longer duration of effect than a single 50-mg dose of enteric-coated diclofenac sodium in patients with moderate to severe pain associated with oral surgery . Compared with 3 doses of enteric-coated diclofenac sodium 50 mg ( 50 mg every 8 hours ) , a single dose of rofecoxib 50 mg provided greater overall analgesic efficacy over 24 hours BACKGROUND ProSorb diclofenac potassium ( K ) is a novel , liquid-filled rapid-dispersion formulation of the nonsteroidal anti-inflammatory drug diclofenac , placed into soft gelatin capsules . Its time to maximal plasma drug concentration has been shown to be approximately half , and its maximal plasma drug concentration nearly twice , that of immediate-release diclofenac K tablets . OBJECTIVE This study compared the analgesic dose-response relationship and tolerability of 3 doses of ProSorb diclofenac K and placebo in the treatment of pain after dental impaction surgery . METHODS This r and omized , double-blind , double-dummy , placebo-controlled parallel-group study was conducted at 6 centers across the United States . Patients aged 18 to 65 years with moderate or severe pain after the removal of > or = 1 impacted m and ibular third molar were r and omly assigned to receive a single dose of ProSorb diclofenac K 25 , 50 , or 100 mg or placebo .  Pain intensity and relief were assessed up to 6 hours after dosing . Rescue treatment was allowed after 1 hour . Efficacy end points included the summed pain intensity difference over 3 and 6 hours ( SPID3 and 6 ) ; total pain relief at 3 and 6 hours ( TOTPAR3 and 6 ) ; median times to onset of perceptible and meaningful relief ( analgesic onset ) and rescue medication use ( analgesic duration ) ; and cumulative percentage of patients using rescue medication . Tolerability was assessed using vital sign measurements and spontaneous reporting of adverse events . RESULTS A total of 265 patients ( 154 women , 111 men ; mean age , 23.3 years ) were enrolled . All 3 ProSorb diclofenac K groups showed higher SPID6 and TOTPAR6 scores and longer median times to rescue medication use than the placebo group ( all , P < 0.001 ) . For these end points , a dose-response relationship was evident between the 100-mg dose and the 25- and 50-mg doses ( P < or = 0.05 ) ; the 25- and 50-mg doses were similar . In the diclofenac groups , median onset times for first perceptible ( < or = 22.5 min ) and meaningful ( < or = 53.0 min ) relief were significantly more rapid than placebo ( P < or = 0.01 ) . Proportions of patients requiring rescue analgesic were < or = 50.8 % with diclofenac compared with 79.4 % with placebo . Proportions of patients assigning a global evaluation of good or better was > or = 68 % with diclofenac compared with 21 % for placebo . Tolerability was similar across all treatment groups . CONCLUSION In this study of patients treated for pain following dental impaction surgery , single doses of ProSorb diclofenac K 25 , 50 , and 100 mg were more efficacious than placebo with respect to reduction of pain . All 3 doses provided a rapid analgesic onset and were well tolerated Pre-emptive analgesic efficacy of the non-steroidal anti-inflammatory drug , diclofenac sodium , was tested in 21 young , fit , patients undergoing third molar extraction s in a double-blind , r and omised , cross-over , trial . Pain scores and mouth opening were observed for 1 week after the operation and these did not show any differences following pre- and postoperative oral administration of diclofenac sodium 100 mg ( P > 0.05 ) . There were no differences in the patients ' preference for the two methods of treatment ( P > 0.05 ) . The study suggests that the non-steroidal anti-inflammatory drug diclofenac sodium does not cause any significant pre-emptive analgesic effects in the dose administered BACKGROUND Safety concerns associated with nonsteroidal anti-inflammatory drugs ( NSAIDs ) have prompted the development of new formulations that minimize adverse events ( AEs ) and maintain efficacy . OBJECTIVES To determine the analgesic efficacy and safety of an investigational , proprietary , nano-formulated , oral diclofenac ( nano-formulated diclofenac ) compared with placebo in subjects with acute dental pain . METHODS A Phase 2 , multisite , r and omized , double-blind , single-dose , parallel-group , active- and placebo-controlled study was carried out in 202 subjects ( 18 - 50 years old ) who had extraction of ≥2 third molars ( ≥1 had to be a fully or partially impacted m and ibular third molar ) and experienced moderate to severe pain intensity ≤6 hours postsurgery ( NCT00985439 ) . Subjects received nano-formulated diclofenac 35 mg or 18 mg , celecoxib 400 mg , or placebo . The primary efficacy variable was the sum of total pain relief ( TOTPAR ) over 0 - 12 hours ( TOTPAR-12 ) after Time 0 . Secondary end points included TOTPAR over 0 - 4 hours ( TOTPAR-4 ) , TOTPAR over 0 - 8 hours ( TOTPAR-8 ) , and time to onset of analgesia . RESULTS Mean ± st and ard deviation TOTPAR-12 for nano-formulated diclofenac 35 mg and 18 mg , celecoxib , and placebo were 16.81 ± 12.76 , 17.76 ± 13.76 , 14.61 ± 15.05 , and 5.65 ± 11.53 , respectively ( P < 0.001 , nano-formulated diclofenac compared with 
    Output:
    
Diclofenac potassium provides good pain relief at 25 mg , 50 mg , and 100 mg doses .
Diclofenac sodium has limited efficacy and should probably not be used in acute pain