***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: To which groups of patients can the results of clinical trials be applied ? This question is often inappropriately answered by reference to the trial entry criteria . Instead , the benefit and harm ( adverse events , discomfort of treatment , etc ) of treatment could be assessed separately for individual patients . Patients at greatest risk of a disease will have the greatest net benefit as benefit to patients usually increases with risk while harm remains comparatively fixed . To assess net benefit , the relative risks should come from ( a meta- analysis of ) r and omised trials ; the risk in individual patients should come from multivariate risk equations derived from cohort studies . However , before making firm conclusions , the assumptions of fixed adverse effects and constant reduction in relative risk need to be checked OBJECTIVE --To determine the sociodemographic and motivational characteristics of  parents who volunteer their children for clinical research . DESIGN --A question naire was administered to parents who volunteered their children for a r and omised , double blind ,  placebo controlled trial of a drug to treat asthma and to a control group of parents whose children were eligible for the trial but had refused the invitation . SETTING --A children 's hospital in Australia . SUBJECTS--68 Parents who had volunteered their children and 42 who had not ; a response rate of 94 % and 70 % , respectively . MAIN OUTCOME MEASURES --Responses of parents to question naire design ed to assess their perceptions , attitudes , and health seeking behaviour as well as sociodemographic data . RESULTS --Volunteering parents were less well educated with only 15 % ( 10/68 ) of mothers and 16 % ( 11/68 ) and of fathers having had a tertiary or university education compared with 26 % ( 11/42 ) of mothers and 45 % ( 19/42 ) in the non-volunteering group . Fewer volunteering parents had professional or administrative jobs than did non-volunteering parents ( mothers 6 % ( 4/68 ) ; fathers 9 % ( 6/68 ) v mothers 14 % ( 6/42 ) ; fathers 31 % ( 13/42 ) ) . Volunteering parents had less social support , and they displayed greater health seeking behaviour and consumed more habit forming substances . They were motivated by a desire to help others and to contribute to medical research , but they were also search ing for more information and better ways to help their own children . CONCLUSION --Parents who volunteer their children for medical research are significantly more socially disadvantaged and emotionally vulnerable We studied the reasons surgical principal investigators chose not to enter patients in a large , multicenter trial sponsored by a cooperative group . In 1976 the National Surgical Adjuvant Project for Breast and Bowel Cancers ( NSABP ) initiated a clinical trial to compare  segmental mastectomy and postoperative radiation , or segmental mastectomy alone , with total mastectomy . Because the low rates of accrual were threatening to close the trial prematurely , we mailed a question naire to the 94 NSABP principal investigators , asking why they were not entering eligible patients in the trial . A response rate of 97 per cent was achieved . Physicians who did not enter all eligible patients offered the following explanations : ( 1 ) concern that the doctor-patient relationship would be affected by a r and omized clinical trial ( 73 per cent ) , ( 2 ) difficulty with informed consent ( 38 per cent ) , ( 3 ) dislike of open discussion s involving uncertainty ( 22 per cent ) , ( 4 ) perceived conflict between the roles of scientist and clinician ( 18 per cent ) , ( 5 ) practical difficulties in following procedures ( 9 per cent ) , and ( 6 ) feelings of personal responsibility if the treatments were found to be unequal ( 8 per cent ) . Further investigation into the behavioral aspects of the investigator-patient relationship is particularly pressing , since fear of change in this relationship was the most common reason given for not entering eligible patients in the trial OBJECTIVE To study characteristics of importance for participation in a diet and physical exercise prevention programme . SETTING Primary Health Care , Sollentuna , and the Karolinska Hospital , Stockholm , Sweden . SUBJECTS A sample of 187 men , aged 35 - 60 , with increased risk factors for CHD , were invited to a 6-month  prevention programme .  Participants ( n = 158 ) were r and omized into a  diet group , a physical exercise group , a diet and physical exercise group , and a control group . Twenty-seven men , who declined participation , formed the group of non participants . DESIGN Participants and non participants were compared with respect to health beliefs , health knowledge , CHD risk factors , demographic and personality factors . MAIN OUTCOME MEASURES Characteristics of men participating and not participating in the intervention trial . RESULTS Non participants , compared with participants , believed less in the benefits of dietary change  and perceived the health threat of stroke and myocardial infa rct ion as less serious . Non participants had a better knowledge of a number of risk factors for cardiovascular disease . CONCLUSION Belief in treatment efficacy and perceived health threat , rather than health knowledge , predicted initial participation in a non-pharmacological intervention trial The problem of generalisability in r and omised clinical trials was highlighted by studies that entered only 10 - 14 % of screened patients . To determine the magnitude and source of prer and omisation losses in clinical trials a survey was conducted of 41 trials listed in the 1979 inventory of the National Institute of Health . Two thirds of the trials maintained screening logs , but only half maintained any records of the number of patients who met the eligibility criteria but were not entered into the trial . Among 21 trials ( 51 % ) that kept data on the number of patients who were eligible but not entered , losses of eligible subjects were attributable to refusals by patients in 25 % and refusals by physicians in 29 % . Other protocol requirements accounted for the remaining losses of eligible patients . Only a few trials documented the characteristics of patients who were eligible but not entered ; in those trials the patients who were not entered were similar demographically but differed clinical ly from those enrolled . Thus minimising prer and omisation losses of eligible patients requires the use of less restrictive criteria for entering patients . Twenty four of the trials achieved 75 % or more of their recruitment goals , eight between 25 % and 74 % , and six less than 25 % . Among trials that screened less than twice their projected sample size , only three out of 13 ( 23 % ) achieved 75 % or more of their recruitment goal . By contrast , 12 out of 16 trials ( 75 % ) that screened more than twice their projected sample size achieved 75 % or more of their recruitment goal . Screening large numbers of patients appears to be a pragmatic requirement for success in achieving recruitment goals ; therefore , trials should not be criticised as lacking generalisability on that basis alone . The number and characteristics of eligible patients who were not entered , however , were documented by only a few trials ; these data are critical in the assessment of generalisability . Additionally , the number of patients with the index disease who did not meet the eligibility criteria should also be documented . Together , these two types of data characterise the population to whom the trial results may be applied This report presents baseline clinical and angiographic data from the Bypass Angioplasty Revascularization Investigation ( BARI ) , a multicenter international trial assessing the relative efficacy of percutaneous transluminal coronary angioplasty ( PTCA ) versus coronary artery bypass graft surgery ( CABG ) in selected patients with multivessel coronary artery disease .  PTCA is commonly performed in patients with multivessel coronary artery disease , yet its long-term efficacy in comparison to CABG is unknown . From August 1988 through August 1991 , 1,829 qualifying patients with multivessel disease suitable for either procedure were r and omized to PTCA or CABG ; sample size estimates were based on anticipated 5-year mortality . Two registry population s were also defined for follow-up : ( 1 ) 2,013 patients eligible for r and omization but not r and omized ; and ( 2 ) 422 patients considered by angiography as unsuitable for r and omization . Patients r and omized in BARI were at relatively high risk for subsequent cardiac events : 39 % were > or = 65 years old , 55 % had prior myocardial infa rct ion , 69 % presented with unstable angina or non-Q wave myocardial infa rct ion , and 43 % had 3-vessel coronary artery disease . Patients r and omized to PTCA and CABG were equally matched in all the important baseline variables . The r and omized and the eligible but not r and omized groups were similar in most respects . However , the nonr and omized group had a higher proportion with college education ; fewer with a history of myocardial infa rct ion , heart failure , diabetes , and smoking ; and a somewhat better average ejection fraction . At the 3-month follow-up , PTCA had been performed more commonly in the nonr and omized eligible patients , especially those with 2-vessel disease . ( ABSTRACT TRUNCATED AT 250 WORDS A r and omised trial of adjuvant chemotherapy vs placebo in operable stomach cancer recruited 249 patients from the West Midl and s Region between 1976 - 1980 . A Cancer Registry survey identified a further 1261 suitable concurrent cases . Trial patients were compared with the 960 non-trial cases from participating Districts . Only 493 ( 51 % ) non-trial cases passed all of the prospect i ve trial selection criteria for entry . Stage and fitness caused the majority of exclusions and were also highly prognostic . A univariate analysis comparing eligible patients with the trial showed the two groups to be balanced for the significant independent prognostic factors of the trial . However , differences in patient age and the surgery performed indicate that recruitment may have been influenced by unknown selection factors . This survey highlights the difficulty of retrospective selection and confirms the need for r and omised controls . Data available from specialist Registries may be used to help develop new protocol s and to verify and extend trial results We surveyed the 270 survivors of acute myocardial infa rct ion who refused to participate in the Warfarin Re-Infa rct ion Study ( WARIS ) . Information on medical variables were derived from registration forms completed by hospital staff upon discharge , whereas data on a variety of health conditions and reasons for refusal were gathered by mailed question naires , 178 ( 66 % ) of which were returned . Some disparities were found when comparing non-respondents and participants , the former showing more potential bad risk factors . The diversities between participants and non-respondents are of yet unknown prognostic importance . However , the presence of such differences imply that information on characteristics of non-respondents in clinical trials is desirable in terms of generalizability of the trial results . Reasons stated for non-participation reflect poor motivation , low mobility and saturation with focusing on disease . A slight co-variation between social status and reasons for refusal was noted The Sosium-Potassium Blood Pressure Trial in Children ( NaKS ) , is a clinical trial in a healthy , free living population of children and adolescents . It is design ed to test the hypotheses that a reduction in dietary sodium and /or an increase in potassium intake will decrease the rate of rise in blood pressure during normal maturation in children and adolescents with high normal blood pressure .  Screening was conducted in 19,452 students in grade s 5 - 8 in Minneapolis and St. Paul between January 1986 and May 1987 . After screening , 3,223 students were found to have blood pressures that fulfilled the initial eligibility criteria for the study , and of these , 643 ( 20.0 % ) attended the orientation meeting , i.e. , the first clinic visit . A total of four clinic visits , design ed to test the willingness and capability of the potential participants to comply with the study protocol were conducted prior to r and omization . At the conclusion of the four prer and omization visits , 243 children ( 7.5 % of the initially eligible children ) agreed to be r and omized to one of four trial groups : low-sodium diet ; potassium supplement administration ; placebo-treated control group ; and a no-treatment control group ( to test the effect of acclimatization on blood pressure measurements ) that will not be seen after r and omization until the 4-year termination of the study . The first participant was r and omized into the study on June 17 , 1986 , and the last on December 29 , 1987 . The potassium and placebo capsules are administered double-masked . Participants will be examined and receive intervention instruction four times yearly for 4 years counted from the date of their r and omization . All groups were comparable with regard to distribution of school district , sex , and race and with respect to baseline physical characteristics . Results from this study will provide information about the feasibility and effect of dietary intervention during childhood and adolescence on the prevention of essential hypertension In EORTC trial 10853 , patients with histologically confirmed surgical clearance of ductal carcinoma in situ ( DCIS ) are being r and omised to observation alone or to receive external radiation to the breast ( 50 Gy ) . So far , 190 patients have been entered from 27 centres . An analysis has been conducted of patients with DCIS presenting to 6 of the participating hospitals . Within these centres there was a total of 216 patients with biopsy confirmed DCIS , without invasion , between 1985 and 1989 . However only 77 ( 36 % ) were entered into the trial . The major reason for non-entry was that DCIS was too extensive ( 76/139 , 55 % ) , so that in situ disease extended to the margins of excision . Other reasons for exclusion included prior breast cancer ( 18 % ) , delay in histological diagnosis ( 
    Output:
    
The effect of patient non-participation appears to depend on whether the RCT is concerned with treatment of an existing condition or with disease prevention .
Participants in treatment trials tend to be more severely ill than those who do not participate .
In contrast , those who participate in prevention trials are more likely to have adopted a healthy lifestyle than those who decline .
Most evaluative studies fail to document adequately the characteristics of those who , while eligible , do not participate .
However , subjects included in RCTs ( i.e. eligible and participating ) tend to have a different prognosis than patients identified from clinical data bases .
Conclusions : Narrow inclusion criteria may offer benefits such as increased precision and reduced loss to follow-up , but there are important disadvantages , such as uncertainty about extrapolation of results , which may result in denial of effective treatment to groups who might benefit , and delay in obtaining definitive results because of reduced recruitment rate .
Selective participation by teaching centres and sicker patients in treatment RCTs may exaggerate the measured treatment effect .
Prevention trials , on the other h and , may underestimate effects as participants have less capacity to benefit