***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: We did a prospect i ve study of women with singleton viable pregnancies at 10 - 13 weeks ' gestation who requested first-trimester fetal karyotyping because of advanced maternal age , parental anxiety , or family history of chromosomal abnormality . Women were counselled as to the available options of non-invasive screening or invasive testing by mid-trimester amniocentesis , early amniocentesis ( EA ) , or chorionic villus sampling ( CVS ) , or r and omisation to EA or CVS at 10 - 13 weeks . EA was done in 731 patients ( 493 by choice and 238 by r and omisation ) and CVS in 570 ( 320 by choice and 250 by r and omisation ) . Both procedures were done by transabdominal ultrasound-guided insertion of a 20-gauge needle . The rate of successful sampling was the same for both procedures ( 97.5 % ) . Spontaneous loss ( intrauterine or neonatal death ) was significantly higher after EA ( total group mean = 5.3 % , 95 % CI 3.8 - 7.2 ; r and omised subgroup mean = 5.9 % , 3.3 - 9.7 ) than after CVS ( total group : mean = 2.3 % , 1.2 - 3.9 ; r and omised subgroup : mean = 1.2 % , 0.3 - 3.5 ) . The gestation at delivery and birthweight of the infants after EA and CVS were similar . In the EA group the incidence of talipes equinovarus ( 1.63 % ) , was higher than in the CVS group ( 0.56 % ) , but this difference was not significant The Emory Angioplasty versus Surgery Trial ( EAST ) showed that multivessel patients eligible for both percutaneous transluminal coronary angioplasty ( PTCA ) and coronary bypass surgery ( CABG )  had equivalent 3-year outcomes regarding survival , myocardial infa rct ion , and major myocardial ischemia .  Patients eligible for the trial who were not r and omized because of physician or patient refusal were followed in a registry . This study compares the outcomes of the r and omized and registry patients . Of the 842 eligible patients , 450 did not enter the trial . Their baseline features closely resembled those of the r and omized patients and follow up was performed using the same methods . In the registry there was a bias toward selecting CABG in patients with 3-vessel disease ( 84 % ) and PTCA in patients with 2-vessel disease ( 54 % ) . Three-year survival for the registry patients was 96.4 % , which was better than the r and omized patients , 93.4 % ( p = 0.044 ) . Angina relief in the registry was equal for CABG and PTCA patients and was better for the PTCA registry ( 12.4 % ) than PTCA r and omized patients ( 19.6 % ) ( p = 0.079 ) . Thus , the registry confirms that EAST is representative of all eligible patients and does not represent a low-risk subgroup . Since baseline differences were small , improved survival in the registry may be due to treatment selection . Physician judgment , even in patients judged appropriate for clinical trials , remains a potentially important predictor of outcomes The objective was to study the generalizability of trial results by comparing  r and omized patients to eligible but nonr and omized patients who received the same management .  Implementation of trial results is only justifiable when the results can be generalized to the total domain population . The design was a multicentre r and omized controlled trial on the effect of early screening and treatment with ventilation tubes on infants with otitis media with effusion . R and omized ( n = 187 ) and nonr and omized eligible patients ( n = 133 ) were followed up . The study population comprised children who were detected by auditory screening at the age of 9 - 12 months and who were subsequently diagnosed with persistent bilateral otitis media with effusion for 4 - 6 months . A significant difference was found in the distribution of some prognostic factors : more r and omized children had older siblings , did not attend day care and had mothers with a lower educational level than the nonr and omized children . These factors , however , did not modify the outcome . No differences were found in mean hearing levels between the r and omized and nonr and omized children : in both the r and omized and nonr and omized children ventilation tubes improved the hearing level , especially after 6 months . However , in the long term ( 12 months ) , the hearing levels were equal again . The results of the r and omized and nonr and omized patients were comparable . The results of this trial appear to be generalizable to the total domain population . The procedure of following up both r and omized and nonr and omized patients is recommended when there is concern about selective participation and reduced generalizability The primary goal of the Prostate , Lung , Colorectal and Ovarian ( PLCO ) Cancer Screening Trial is to learn whether widespread use of screening tests to detect these cancers will reduce associated mortality .  Blacks have the highest age-adjusted cancer incidence and mortality rates of any population group in the United States , but several barriers to their participation in clinical research such as the PLCO trial exist . These barriers involve sociocultural , economic , and individual factors , as well as factors inherent in trial design s. Population diversity in the PLCO trial is necessary to preserve scientific validity and generalizability of trial results . Therefore , the National Cancer Institute and the Centers for Disease Control and Prevention are collaborating to ensure adequate representation of blacks in the PLCO trial . For example , the agencies have funded several new activities design ed to better underst and and overcome barriers to participation in the trial . These activities include the African American Men Project , a r and omized trial design ed to evaluate the efficacy of three increasingly intensive recruitment interventions in recruiting black men ; the establishment of a minority-focused PLCO trial screening center , a study to identify factors that influenced the decisions of black women recruited to participate in the PLCO trial ; and a study to examine the psychosocial factors that influence blacks ' decision making to engage in cancer screening and participation in research similar to the PLCO trial . The results of these activities will allow for a more thorough examination of cancer-related issues of importance to blacks and will help shed light on factors that influence their decisions to participate in cancer screening and prevention clinical trials In clinical research , r and omized trials are widely accepted as the definitive method of evaluating the efficacy of therapies . R and om assignment of patients to treatment ensures internal validity of the comparison of new treatments with controls . An assessment of external validity can best be achieved by comparing the r and omized study sample to the population of patients who met the eligibility criteria but did not consent to r and omization . The Comprehensive Cohort Study ( CCS ) is design ed to recruit all patients fulfilling the clinical eligibility criteria regardless of their consent to r and omization .  The CCS concept was adopted in the major clinical trials of the German Breast Cancer Study Group ( GBSG ) conducted between 1983 and 1989 . In this period 124 centres recruited 2084 patients in three clinical trials . 734 ( 35 per cent ) of these patients accepted being r and omized , while 1350 ( 65 per cent ) chose one of the treatments under study ; the r and omization rates differed remarkably between trials . In this paper we examine the representativeness of the r and omized patients in the three trials . Based on a median follow-up of about 5 years we present results on the external validity of the treatment effects estimated in the r and omized patients by means of Cox 's proportional hazards model and compare them between trials . We discuss advantages and disadvantages of the CCS design and conclude that its use is only justified under extraordinary circumstances Of 90 patients with intermediate or high- grade sarcoma eligible for a r and omized trial of adjuvant doxorubicin ( Adriamycin , Adria Laboratories , Columbus , Ohio ) , 48 were not entered : 24 ( 27 % ) by physician 's choice and 24 refused r and omization . Sixty-five percent of lower stage patients were r and omized compared with 37 % of those with higher stage ( P = .02 ) . Patients with extremity lesions were more frequently offered participation in the study ( P = .07 ) . Patients with lower stage lesions accepted  r and omization  more readily than those with higher stage lesions ( P = .01 ) . As predicted by the higher stage and percentage of central lesions , the disease-free survival of nonr and omized patients was inferior to that of r and omized patients ( P = .15 ) . Thus , patients at high risk appeared to avoid r and omization and adjuvant doxorubicin in this trial , result ing in an inferior disease-free survival for the nonr and omized control group . Important questions generally require r and omized trials that reliably determine relative treatment differences . If , however , the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases , the generalizability of the results to the entire patient population may be compromised . For example , the prognosis of the general population can not necessarily be inferred from the selected group in the study . In this study , the r and omized and nonr and omized series yielded differing conclusions regarding treatment efficacy , even when an adjustment was made for known prognostic facts This paper reports on the reasons why patients agreed to or declined entry into r and omized trials of cancer following discussion s conducted by clinicians in both District General and University Hospitals . Two hundred and four patients completed a 16-item question naire following the consultation , of these 112 ( 55 % ) were women with breast cancer . Overall results showed that 147 ( 72.1 % ) patients accepted entry to a r and omized clinical trial ( RCT ) . The main reasons nominated for participating in a trial were that ‘ others will benefit ’ ( 23.1 % ) and ‘ trust in the doctor ’ ( 21.1 % ) . One of the main reasons for declining trial entry was that patients were ‘ worried about r and omization ’ ( 19.6 % ) . There was a significantly higher acceptance rate for trials providing active treatment in every arm 98 ( 80.6 % ) compared with those trials with a no treatment arm 46 ( 60.5 % ) , χ2test P = 0.003 . The study outlines a number of factors that appear to influence a patient ’s decision to accept or decline entry into an RCT of cancer therapy . An important factor is whether or not the trial offers active treatment in all arms of the study . Communication that promotes trust and confidence in the doctor is also a powerful motivating influence . © 2000 Cancer Research In the Antiarrhythmics Vs Implantable Defibrillators ( AVID ) trial , all patients who meet the study entry criteria are followed in a registry . During the period between June 1993 and June 1995 , of 1,117 patients who were enrolled in the registry and met the study entry criteria , 476 were r and omized to receive either implantable cardioverter-defibrillators ( ICDs ) or drug therapy ( amiodarone or sotalol ) , and 641 patients were not r and omized for a variety of reasons including : patient refusal ( 42 % ) ; physician refusal ( 43 % ) ; concerns about ability to maintain follow-up over several years ( 10 % ) , and others ( 6 % ) . There were no significant differences between the 476 r and omized and 641 nonr and omized patients with regard to clinical characteristics , left ventricular function , history of congestive heart failure , medical history , and previous cardiac procedures performed before the index event , except that r and omized patients were slightly older ( 65 vs 62 years ) and had a slightly higher prevalence of coronary artery disease and previous myocardial infa rct ion . The index event and location of the index event were not significantly different between the 2 groups . Although 14 % of registry patients received neither  ICD nor antiarrhythmic drug therapy , ICDs were no more frequently used in the registry patient than  antiarrhythmic drugs  ( 45 % for ICD vs 42 % for drugs ) . Thus , r and omized AVID patients have very similar clinical characteristics , cardiac history , and presenting arrhythmias as to nonr and omized eligible patients . Therefore , the results of the AVID trial may be generalized for all patients with AVID-eligible arrhythmias BACKGROUND In many countries , surgical uterine evacuation is the st and ard treatment for women with a miscarriage , but expectant management has been advocated as an alternative . The choice between the two options can not be based on published evidence alone , because r and omized clinical trials are scarce while generalizability of findings to patients with a strong preference for either management options is unclear . METHODS In a r and omized controlled trial , the complications and efficacy of either expectant or surgical management for miscarriages were compared , and the results in patients who refused r and omization and were managed according to their own preference were studied . In total , 122 patients were r and omized and 305 were managed according to their choice . RESULTS No differences were found in the number of emergency curettages and complications between expectant and surgical management .  Efficacy at 6 weeks was 30/64 ( 47 % ) in women allocated to expectant management , and 55/58 ( 95 % ) in women allocated to surgical evacuation . After 7 days , 37 % of expectantly managed women had a spontaneous complete miscarriage . After 6 weeks , intention-to-treat analysis including cross-overs showed similar effectiveness ( 92 % versus 100 % ) . Results in the preference groups were comparable with those in the r and omized groups . CONCLUSION In our experience a waiting period of 7 days after diagnosis may prevent 37 % of surgical procedures We studied the reasons surgical principal investigators chose 
    Output:
    
These findings suggest that r and omized treatment assignment as part of a clinical trial does not harm research participants