***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 BACKGROUND Genital warts are a common sexually transmitted disease caused by human papillomavirus . Imiquimod is a novel immune-response modifier capable of inducing a variety of cytokines , including interferon alfa , tumor necrosis factor-alpha , as well as interleukins 1 , 6 , and 8 . In animal models imiquimod has demonstrated antiviral , antitumor , and adjuvant activity . In vitro , imiquimod has no antiviral or antitumor activity . OBJECTIVE Our purpose was to determine the safety and efficacy of topical imiquimod for the treatment of external genital warts .  METHODS This prospect i ve double-blind , placebo-controlled , parallel design clinical trial was performed in three outpatient centers , a public health clinic , a university-based clinic , and a private practice . One hundred eight patients with external genital warts ( predominantly white men ) were entered into the trial . Fifty-one patients were r and omly selected to receive  5 % imiquimod cream ; 57 patients were r and omly chosen to receive placebo cream .  Study medication was applied three times weekly for up to 8 weeks . Patients whose warts cleared completely were observed for up to 10 weeks to determine recurrence rates . RESULTS In the intent-to-treat analysis , the warts of 37 % ( 19 of 51 ) of the imiquimod-treated patients and 0 % ( 0 of 57 ) of the placebo group cleared completely ( p < 0.001 ) . In addition , many patients experienced a partial response . A reduction in baseline wart area of 80 % or more was observed in 62 % of imiquimod-treated patients ( 28 of 45 ) and 4 % of the placebo group ( 2 of 50 ) ( p < 0.001 ) ; a 50 % reduction or more in wart area was noted in 76 % of imiquimod-treated patients ( 34 of 45 ) and 8 % of placebo recipients ( 4 of 50 ) ( p < 0.001 ) . Of imiquimod-treated patients whose warts cleared completely and who finished the 10-week follow-up period , 19 % ( 3 of 16 ) experienced recurrences of warts .  Imiquimod-treated patients experienced a significantly greater number of local inflammatory reactions than the placebo group . Symptoms and signs associated with the local inflammatory reactions included itching ( 54.2 % ) , erythema ( 33.3 % ) , burning ( 31.3 % ) , irritation ( 16.7 % ) , tenderness ( 12.5 % ) , ulceration ( 10.4 % ) , erosion ( 10.4 % ) , and pain ( 8.3 % ) . There were no differences in systemic reactions or laboratory abnormalities between treatment groups . CONCLUSION Topical 5 % imiquimod cream appears to have a significant therapeutic effect in the treatment of external genital warts BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences OBJECTIVE To compare the safety and effectiveness of 5 % and 1 % imiquimod cream with vehicle cream in the treatment of external anogenital warts . DESIGN R and omized , double-blind , placebo-controlled comparison that evaluated patients for total clearance of their warts . Patients who experienced total clearance were evaluated for recurrence in a 12-week follow-up . SETTING Eleven ambulatory offices , including both private physician offices and referral medical centers . PATIENTS Three hundred eleven healthy men and women aged 18 years or older with 2 to 50 external anogenital warts were recruited from the practice s of investigators , referring physicians , and advertisements . Eighty-two additional patients were screened but did not qualify . Four patients discontinued use of the medication because of adverse effects . INTERVENTIONS Five percent imiquimod ( Aldara ) cream , 1 % imiquimod cream , or vehicle cream was applied to all external warts overnight 3 times each week for 16 weeks , or until all treated warts disappeared , whichever occurred first . MAIN OUTCOME MEASUREMENTS The number of patients experiencing the elimination of all baseline warts and the recurrence rate of these warts . In addition , the reduction in baseline wart area the duration of therapy required to eliminate warts , and the frequency and severity of adverse reactions were principal measurements . RESULTS In the intent-to-treat analysis , 54 ( 50 % ) of 109 patients who received 5 % imiquimod cream , 21 ( 21 % ) of 102 of those who received 1 % imiquimod cream , and 11 ( 11 % ) of 100 patients treated with vehicle cream experienced eradication of all treated baseline warts . The difference between the effectiveness of 5 % imiquimod cream and the vehicle cream was statistically significant ( P < .001 ) . Of those patients whose warts cleared during therapy , 13 % of patients who received 5 % imiquimod experienced a recurrence of at least 1 wart . Recurrences occurred in none of the patients who used 1 % imiquimod cream and in 10 % of patients who used the vehicle cream .  Local erythema was the most common adverse reaction , but the majority of patients in each group experienced no or only mild local inflammatory reactions . There were no differences in incidences of flulike symptoms among treatment groups . CONCLUSIONS Five percent imiquimod cream is an effective and safe self-administered therapy for external anogenital warts when applied 3 times a week overnight for up to 16 weeks . The recurrence rate is low This dose-escalation study was performed to evaluate safety and efficacy of imiquimod 5 % cream in the treatment of uncircumcised men with penile warts associated with the foreskin . The cream was applied 3 times/week ( n=34 ) or once per day ( n=30 ) over 8 ± 2h . Imiquimod 5 % cream was safe in both treatment groups . However , the 3 times/week regimen was better tolerated with a lower incidence of local skin reactions . In both groups , the 2 most frequently reported local skin reactions were erythema and erosion ; they were more severe with the once-daily dosing . The most frequently reported application site reactions were burning , pruritus and irritation or pain ( once-daily patients only ) . Total clearance was achieved in 62 % of the patients in the 3 times/week group and by 57 % in the once-daily group . Thus , imiquimod 5 % cream administered 3 times/week was the optimal dosing regimen in the treatment of penile warts in uncircumcised men As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 
    Output:
    
Imiquimod is effective in home application , though not in patients with HIV infection with the evidence presently available