***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 OBJECTIVE To evaluate the efficacy and tolerability of aceclofenac , 200 mg/day , and paracetamol , 3000 mg/day , in the treatment of osteoarthritis ( OA ) of the knee . METHODS This was a double-blind , parallel-group , multicentre clinical trial involving patients with symptomatic OA of the knee , conducted in Spain . Patients were r and omly allocated to aceclofenac 100 mg twice daily ( n=82 ) or paracetamol 1000 mg three times daily ( n=86 ) . Patients were assessed at baseline and 6 weeks . Primary efficacy measures were severity of pain ( visual analogue scale , VAS ) , Lequesne OA knee index , and patient 's and physician 's global assessment of disease activity . Severity of knee pain at rest or walking , stiffness , knee swelling and tenderness , and assessment of health-related quality of life ( Health Assessment Question naire , Western Ontario and McMaster Universities Osteoarthritis Index , and Short Form 36 ) were included as secondary endpoints . RESULTS Both treatment groups showed significant improvement compared with their baseline values in the four primary endpoints . Mean between-treatment differences favoured aceclofenac over paracetamol on pain ( VAS , 7.64 mm [ 95 % confidence interval ( CI ) , 0.44 - 14.85 mm ] ) , Lequesne OA index ( 1.41 [ 95 % CI , 0.45 - 2.36 ] ) , and patient 's ( 0.33 [ 95 % CI , 0.06 - 0.61 ] ) and physician 's ( 0.23 [ 95 % CI , 0.01 - 0.47 ] ) global assessment s. Adverse events were similar for both drugs ( paracetamol , 29 % patients vs aceclofenac , 32 % ; P=0.71 ) . Four patients withdrew in each group due to adverse events . Patients tended to prefer aceclofenac to paracetamol ( P=0.001 ) , and more treated with paracetamol withdrew from the study due to lack of efficacy ( n=8 vs n=1 , P=0.035 , for paracetamol and aceclofenac , respectively ) . CONCLUSION At 6 weeks , patients with symptomatic OA of the knee showed a greater improvement in pain and functional capacity with aceclofenac than paracetamol with no difference in tolerability & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with  placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics .  Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data OBJECTIVE To determine the analgesic efficacy and safety of a single oral dose of aceclofenac 100 mg and compare that with placebo and naproxen 500 mg in women with primary dysmenorrhoea . STUDY DESIGN In this double-blind , prospect i ve , multicentre , r and omised , three-way , crossover study , women were r and omly assigned to receive one of six treatment sequences , comprising single oral doses of aceclofenac 100 mg , naproxen 500 mg or placebo , when menstrual pain reached a predetermined level of severity . A single dose of the assigned study medication was taken on three menstrual periods ; a different medication was taken on each treatment day . Analgesic efficacy was determined by self-reported analgesia scoring and participants ' and investigators ' global evaluation of treatment effectiveness . Measurements also included physical examination and adverse events . RESULTS Total pain relief scores were not statistically significantly different for aceclofenac and naproxen , and both were statistically significantly more effective than placebo ( p = 0.019 and 0.002 , respectively ) . This finding was supported by secondary endpoints including sum of pain intensity differences ( SPID/8 ) , peak analgesia ( peak pain intensity and peak pain relief ) , and participants ' and investigators ' overall evaluation of effectiveness . Both aceclofenac and naproxen were well tolerated . CONCLUSIONS Aceclofenac ( 100 mg ) and naproxen ( 500 mg ) effectively treated the pain associated with primary dysmenorrhoea , and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria The aim of the present placebo-controlled , double-blind study was to evaluate the comparative efficacy of single doses of aceclofenac 150 mg and ibuprofen 400 mg in 217 patients with postoperative pain after third molar surgery . Outcome of primary efficacy was judged by overall assessment of the area under the curve ( AUC ) of graphs for pain intensity ( AUC pain ) pain relief ( AUC relief ) , both measured from serial visual analogue scales over a 6 h investigation period . Other measures of efficacy included the rate of pain reduction in the first hour , the number of patients who took ' escape ' analgesics and the time before they did , and an overall assessment of pain relief score on a five-point categorical scale . Ibuprofen 400 mg was significantly superior to placebo for pain relief ( P < 0.01 ) , degree of pain reduction in the first hour ( P = 0.005 ) , and the number of patients who required escape analgesia ( P < 0.001 ) , and the time before they did ( P < 0.001 ) . The outcome for patients treated with aceclofenac 150 mg was not significantly different from that of patients treated with placebo ( P > 0.05 ) . A single dose of ibuprofen 400 mg provided significant pain relief in the early postoperative period after third molar surgery , whereas a single dose of aceclofenac 150 mg was not effective in the management of postoperative pain after this operation The analgesic efficacy and safety of a single oral dose of 100 mg of aceclofenac was compared in a double-blind study with a single dose of 650 mg of paracetamol in patients with severe episiotomal pain . The patients were question ed after 30 min and then at hourly intervals for 6 h after medication . A st and ard format ( Huskisson 's test ) was used to investigate the intensity of the pain throughout the study . The statistically significant results show that the analgesic effect of aceclofenac is superior to that of paracetamol . The tolerance of both compounds is excellent & NA ; A data base of r and omised  clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed ABSTRACT Objective : Osteoarthritis is one of the most common forms of arthritis seen in primary care . Non-steroidal anti-inflammatory drugs ( NSAIDs ) play an important role in the management of osteoarthritis . However , gastrointestinal ( GI ) side effects limit their use . Cyclooxygenase-2 ( COX‐2 ) selective inhibitors exhibit better GI tolerability than conventional NSAIDs , but their cardiovascular safety is controversial . An NSAID with high efficacy , high GI tolerability and devoid of adverse cardiovascular effects is therefore a profile preferred by physicians . Aceclofenac is an anti-inflammatory and analgesic drug with preferential COX-2 inhibition . The objective of this study was to assess the efficacy and safety of aceclofenac in the treatment of osteoarthritis in an Indian population . Research design and methods : The trial was controlled , comparative , r and omized , and double-blind . The study included 247 patients ( 82 males and 165 females , 40–82 years ) , suffering from osteoarthritis . Patients were r and omized to receive either aceclofenac ( 100 mg twice daily ) or diclofenac ( 75 mg twice daily ) . Main outcome measures : Clinical assessment was done at screening , r and omization , and at 2 weeks , 4 weeks and 8 weeks of treatment by calculating Western Ontario MacMaster ( WOMAC ) scores , time taken to walk 100 feet , visual analogue scores for pain , investigator 's assessment on a Likert scale and joint tenderness . 
    Output:
    
AUTHORS ' CONCLUSIONS In the absence of evidence of efficacy for oral aceclofenac in acute postoperative pain ( at least at 150 mg single dose ) , its use in this indication is not justified .