You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Size is everything – large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects
Abstract 1:
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


Title 2:
Alleviation of wound pain after surgeries for obstructive sleep apnea.
Abstract 2:
OBJECTIVES There has been growing awareness that alleviation of wound pain and associated symptoms after obstructive sleep apnea ( OSA ) surgeries may improve the quality of care . We performed a hospital-based study to compare the effectiveness and safety of two different regimens in the treatment of postoperative pain . STUDY DESIGN A prospect i ve , r and omized , and parallel-group study . METHODS Ninety OSA patients were enrolled for surgical treatments in this study . Forty-five patients ( group 1 ) were r and omized to receive intravenous ketorolac and another 45 patients ( group 2 ) were given the conventional regimen of oral mefenamic acid and intramuscular meperidine after  OSA surgeries for 3 days at hospital . Postoperative discomfort was measured by a self- assessment question naire on the 1st and 3rd days after surgery . Any adverse effect of pain treatment was carefully monitored . Patients ' satisfaction with postoperative pain treatment was evaluated 1 month postoperatively . RESULTS On the 1st postoperative day , group 1 patients had a significantly lower mean score in six out of eight pain-related symptoms than group 2 patients had ( P<.05 ) . At the 3rd postoperative day , significant differences remained for two symptoms . Group 1 patients were generally more satisfied with their pain treatment than were group 2 patients ( P=.01 ) . Increased risk of postoperative bleeding for group 1 was not observed in this study . CONCLUSIONS A short-term administration of intravenous ketorolac is noninferior to the conventional regimen and represents a safe and effective treatment for wound pain , particularly in the 1st day , after OSA surgeries in selected patients


Title 3:
Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics: verification from independent data
Abstract 3:
Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score  ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . 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 in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form


Title 4:
Analgesic Effect of Aspirin, Mefenamic Acid and Their Combination in Post-Operative Oral Surgery Pain
Abstract 4:
A double-blind r and omized single dose study of the analgesic effects of 650 mg aspirin , 250 mg mefenamic acid , the combination of 650 mg aspirin and 250 mg mefenamic acid and placebo on 120 patients with pain following oral surgery was conducted . Patients evaluated their pain intensity and extent of pain relief at 1 , 2 , 3 and 4 h after drug administration . For most parameters , including the sum of the pain intensity differences and the sum of the hourly pain relief scores , each of the drugs was more effective than placebo . Aspirin – mefenamic acid in combination was more effective than both drugs alone , and aspirin and mefenamic acid alone were equally effective for most of the analgesic variables


Title 5:
Double-blind comparison of piroxicam and mefenamic acid in the treatment of oral surgical pain.
Abstract 5:
Single doses of piroxicam ( 20 mg ) and mefenamic acid ( 500 mg ) were compared , double-blind , for analgesic effectiveness in the treatment of oral surgical pain in out- patients . Excluding placebo responders and patients with mild or no baseline pain , 118 cases ( 57 piroxicam , 61 mefenamic acid )  were analyzed for efficacy . The treatments were statistically equivalent and highly effective ; over 75 % of patients in both groups reported a reduction of 2 points or more in pain severity . The percentage of patients reporting complete relief of severe pain was slightly higher for piroxicam , the onset of analgesic activity was equivalent , and side effects were infrequent ( 5 % ) and mild with both medications . Piroxicam was clearly efficacious in relieving  post-exodontic pain .  If these findings are confirmed in other painful conditions and safety on extended use is established , piroxicam should prove quite useful as a general analgesic for the treatment of a wide variety of painful conditions


Title 6:
Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics
Abstract 6:
& 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


Title 7:
Control of pain resulting from endodontic therapy: a double-blind, placebo-controlled study.
Abstract 7:
The efficacy of mefenamic acid , aspirin , and a placebo for control of  postendodontic pain  was compared in a double-blind , r and omized study of 150 patients . Medication was begun immediately prior to the endodontic therapy and continued for a total of eight doses . The results were analyzed in terms of the patients ' assessment s of postendodontic pain , the need for additional analgesic medication , and the patients ' and investigator 's evaluations of drug efficacy . The results indicate that mefenamic acid was well tolerated .  Mefenamic acid was equal to , or exceeded , aspirin in ability to control postendodontic pain in every comparison made . The converse was never true . Mefenamic acid was statistically superior to placebo in every comparison made . Aspirin was not consistently superior to the placebo . Under the conditions of this trial , it can be stated that , for control of pain following simple endodontic therapy , mefenamic acid rather than aspirin is the drug of choice


Title 8:
Developing a database of published reports of randomised clinical trials in pain research 
Abstract 8:
& 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


Title 9:
The visual analogue pain intensity scale: what is moderate pain in millimetres?
Abstract 9:
Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics .  Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain .  The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale


Title 10:
Comparison of two formulations of lignocaine spray with mefenamic acid in the relief of post-episiotomy pain: a placebo-controlled study.
Abstract 10:
The analgesic effectiveness of aqueous and alcoholic formulations of lignocaine ( 5 % ) spray was compared with that of mefenamic acid ( 500 mg ) or placebo in a double-blind study in 103 primiparous patients complaining of moderate or severe perineal pain associated with episiotomy . The results , assessed after a single dose , showed that the aqueous lignocaine formulation provided a level of pain relief superior to that obtained with the alcoholic formulation or placebo , and similar to that obtained with mefenamic acid


Title 11:
Control of pain by mefenamic acid following removal of impacted molar. A double-blind, placebo-controlled study.
Abstract 11:
The efficacy of mefenamic acid , aspirin , and placebo in the control of  postsurgical pain  was compared in a double-blind , r and omized study of forty-seven patients . Medication was begun as soon as the anesthetic began to wear off and was continued as needed to a maximum of eight doses over a 48-hour period . The results were analyzed in terms of the patient 's assessment of postsurgical pain , and the patient 's and the investigator 's evaluation of drug efficacy . In the population studied , mefenamic acid was well tolerated .  Mefenamic acid was clearly superior to placebo and equalled or exceeded the ability of aspirin to control postsurgical pain in the parameters measured
Oral mefenamic acid 500 mg was effective at treating moderate to severe acute postoperative pain , based on limited data .