***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 
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    Input: Background : Information on major harms of medical interventions comes primarily from epidemiologic studies performed after licensing and marketing . Comparison with data from large-scale r and omized trials is occasionally feasible . We compared evidence from r and omized trials with that from epidemiologic studies to determine whether they give different estimates of risk for important harms of medical interventions . Methods : We targeted well-defined , specific harms of various medical interventions for which data were already available from large-scale r and omized trials ( > 4000 subjects ) . Nonr and omized studies involving at least 4000 subjects addressing these same harms were retrieved through a search of MEDLINE . We compared the relative risks and absolute risk differences for specific harms in the r and omized and nonr and omized studies . Results : Eligible nonr and omized studies were found for 15 harms for which data were available from r and omized trials addressing the same harms . Comparisons of relative risks between the study types were feasible for 13 of the 15 topics , and of absolute risk differences for 8 topics . The estimated increase in relative risk differed more than 2-fold between the r and omized and nonr and omized studies for 7 ( 54 % ) of the 13 topics ; the estimated increase in absolute risk differed more than 2-fold for 5 ( 62 % ) of the 8 topics . There was no clear predilection for r and omized or nonr and omized studies to estimate greater relative risks , but usually ( 75 % [ 6/8 ] ) the r and omized trials estimated larger absolute excess risks of harm than the nonr and omized studies did . Interpretation : Nonr and omized studies are often conservative in estimating absolute risks of harms . It would be useful to compare and scrutinize the evidence on harms obtained from both r and omized and nonr and omized studies Background We aim ed to determine the representation of elderly people in published reports of r and omized controlled trials ( RCTs ) . We focused on trials of 4 medications — pioglitazone , rosuvastatin , risedronate , and valsartan — frequently used by elderly patients with chronic medical conditions . Methods and Findings We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest . Estimates of the community-based “ on-treatment ” population were from a national health insurance data base ( SNIIR-AM ) covering approximately 86 % of the population in France . From this data base , we evaluated data cl aims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months . Of the 155 RCT reports selected , only 3 studies were exclusively of elderly patients ( 2 assessing valsartan ; 1 risedronate ) . In only 4 of 37 reports ( 10.8 % ) for pioglitazone , 4 of 22 ( 18.2 % ) for risedronate , 3 of 29 ( 10.3 % ) for rosuvastatine and 9 of 67 ( 13.4 % ) for valsartan , the proportion of patients aged 65 or older was within or above that treated in clinical practice . In 62.2 % of the reports for pioglitazone , 40.9 % for risedronate , 37.9 % for rosuvastatine , and 70.2 % for valsartan , the proportion of patients aged 65 or older was lower than half that in the treated population . The representation of elderly people did not differ by publication date or sample size . Conclusions Elderly patients are poorly represented in RCTs of drugs they are likely to receive Context Prescription and management of medications are important issues for older adults . Contribution Among elders enrolled in two managed care organizations , most quality problems were related to failure to prescribe indicated medications ; failure to monitor medications ; and failure to provide medication along with proper documentation and education in concert with other physicians . Implication s Prescribing inappropriate medications for older adults is less of an issue than other aspects of drug therapy . Quality improvement efforts should focus on avoiding errors of omission in prescribing indicated medications , monitoring , patient education , and follow-up . The Editors Pharmacotherapy is an essential component of medical treatment for older patients , but medications are also responsible for many adverse events in this group . Ninety percent of people 65 years of age or older take at least one medication ( 1 ) . This age group , which represents only 13 % of the population , accounts for one third of all prescription drug expenditures in the United States ( 2 ) . Many older persons take multiple drugs for the treatment of several conditions , which increases the chance of adverse drug reactions , drugdrug interactions , and drugdisease interactions . The frequency of adverse drug events in elderly out patients ranges from 10 % to 35 % , depending on the setting ( 3 - 5 ) . Recognizing the magnitude of medication-related issues , panels of geriatric experts rate medication problems among the most important quality -of-care problems for older patients ( 6 - 8 ) . Reflecting the severity and frequency of adverse drug events in older patients , many investigations have focused on the appropriateness of medication prescribing to elderly persons . Implicit review mechanisms include the Medication Appropriateness Index , which consists of 10 medication characteristics ( including indication , effectiveness , and dosage ) that a trained pharmacist review er can judge as appropriate , marginally appropriate , or inappropriate . An application of the Medication Appropriateness Index to elderly veterans taking 5 or more prescription medications found that 74 % had at least 1 inappropriate aspect to their prescriptions ( 9 , 10 ) . Review s using explicit criteria usually focus on medications that should be avoided in the care of older patients . The list of medications to avoid , which was developed by Beers and colleagues on the basis of a formal consensus of geriatric experts ( 11 - 13 ) , has been applied to various groups of patients , revealing a high prevalence of inappropriate drug use ( 14 - 20 ) . In addition , explicit criteria about drugdrug interactions , treatment duration , and drug contraindications were created by Tamblyn and colleagues and applied to medications prescribed to older patients in Canada ( 21 ) . They found that more than half of older patients took at least one high-risk medication . Health policy efforts , on the other h and , have focused predominantly on finding ways to pay for the medication needed by older patients . Proposals aim to improve access to pharmacologic care but do not strive to develop mechanisms to evaluate or improve the quality of medication management for older patients . Improvement in access to medications without quality assurance may result in a mere increase in care without change in outcomes . To provide a more comprehensive evaluation of the quality of pharmacologic care for older patients , we systematic ally evaluated medication management for a sample of older patients by taking advantage of a set of explicit process of care quality indicators developed and implemented in the Assessing Care of Vulnerable Elders ( ACOVE ) project ( 22 ) . Whereas the earlier ACOVE analysis described overall quality of care and compared care quality for geriatric and medical conditions , this study focuses on pharmacologic care and identifies improvement needs in medication management . Our quality evaluation covered the continuum of pharmacologic care , from recognizing the indications for medications to choosing medication , prescribing appropriately , educating and documenting , and monitoring after prescribing . Methods The ACOVE project developed a set of explicit quality indicators  to evaluate the care provided to vulnerable older persons ( 22 - 24 ) . The system focuses on processes of care within the domains of prevention , diagnosis , treatment , and follow-up and covers the spectrum of care contained in 22 conditions that are important in the care of older patients ( 7 ) . The methods for selecting conditions and developing the quality indicators are described in detail elsewhere ( 7 , 23 ) . Methods included systematic literature review s and multiple layers of expert judgment ( 23 ) . The literature review result ed in proposal of c and i date quality indicators , which were review ed by an expert panel that rated each of the proposed quality indicators for validity and feasibility . This set was modified and approved by a clinical committee of national geriatric experts and by the American College of Physicians Task Force on Aging ( 24 ) . From the final ACOVE set of quality indicators , 43 quality indicators ( Table 1 and Appendix Table ) that pertained to pharmacologic care and had more than 5 eligible patients are included in this analysis . Table 1 .  Medication Quality Indicators , Number of Eligible Patients , and Pass Rates Patients and Data Collection We assessed care provided to older persons who were enrolled in 2 managed care organizations . Each managed care organization , one in the U.S. Northeast and the other in the Southwest , had more than 20 000 senior enrollees and contracted with a network of providers to deliver care . A r and om sample of community-dwelling persons 65 years of age or older was drawn from enrollees in each managed care organization . Eligibility criteria included continuous enrollment in the managed care organization for at least 13 months , no out-of-plan care , and no active treatment for malignant conditions ( excluding nonmelanoma skin cancer ) during the period . In addition , persons who did not speak English were excluded because our interview instruments were not available in other language s. Among the enrollees , we targeted vulnerable elders , defined as persons 65 years of age and older who are at increased risk for death or functional decline . Vulnerable elders were identified on the basis of self-report ( or proxy report ) by using a brief screening survey ( the Vulnerable Elders-13 [ VE-13 ] Survey [ 25 ] ) administered by telephone . The R AND Institutional Review Board approved the study protocol . Data were derived mainly from abstract ing medical records . For participating patients , we identified all inpatient and outpatient medical records during the 13-month period of 1 July 1998 to 31 July 1999 . These medical records were abstract ed by trained nurses with experience in quality assessment . The abstract or considered all of a patient 's medical records when assessing whether a patient was eligible for and received the indicated care processes . Information on eligibility for a quality indicator could be derived from one medical record ( such as a primary care physician starting an appropriate antidepressant ) and the care process delivered and documented from records in another setting ( such as a psychiatric consultant escalating the antidepressant dosage in response to lack of improvement ) . A senior nurse- review er assessed each completed medical record abstract , and physician overreaders review ed quality indicators that required a clinical assessment , such as whether there was follow-up to newly started long-term therapy with a medication or whether newly started therapy with a highly anticholinergic drug had acceptable alternatives . We evaluated inter-rater reliability by re- abstract ing a r and om sample of 10 % of the medical records . These records contained 698 quality indicators ; 97 % had identical eligibility and 95 % demonstrated identical eligibility and score . Details of study enrollment and data collection can be found elsewhere ( 22 ) . Because some aspects of care might not be adequately captured in the medical record ( for example , patient education about medications ) , these data were supplemented by a quality -of-care interview with study participants ( or , if necessary , their proxies ) . During the interview , patients were asked to list all of their medications . On the basis of conditions and medications reported during the interview , patients were asked about specific processes of care they had received . The interview was conducted by telephone  between August and October 2000 . To minimize recall bias , we asked about most recent care when implementing quality indicators that may include multiple events ( for example , education about newly started therapy with a medication ) . Information was obtained from medical records for 37 quality indicators and from the patient interview for 6 quality indicators .  For 4 quality indicators reported previously by using medical record data ( 22 ) , we used interview data in this analysis because subsequent evaluation revealed that interview data on information transfer quality indicators yielded higher pass rates that were aligned with a priori hypotheses and provided more conservative estimates of quality of care . Statistical Analysis A  quality indicator  was scored for a patient if he or she met the eligibility criteria to receive the specified care process . The quality indicator was passed if the care process was implemented for the patient . If the medical record indicated that the patient declined the care process , the quality indicator was considered to be passed . On the other h and , if the patient had a prespecified contraindication to the care process ( such as a patient with asthma who otherwise was eligible to receive a -blocker after a myocardial infa rct ion ) , the patient was considered ineligible for the quality indicator . Quality scores were calculated as the proportion of eligible patients who received indicated care . Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Frail older people have been systematic ally excluded from r and omised controlled trials ( RCT ) . We aim to recruit older , frail hospitalised patients in an RCT and evaluate the frailty index ( FI ) as a measure to describe the types of people included in the study . We recruited 315 hospitalised patients aged 65 years ; age ranged from 60 to 102 years . Baseline assessment scores ranged as follow : Mini‐Mental Status Examination from 7 to 30 , Barthel index from 5 to 100 and FI from 2 to 24 . Total deaths were 20 ( 6 % ) . We demonstrated that it is feasible to recruit frail older people into RCTs . The FI does not show any ‘ floor ’ or ‘ ceiling ’ effects . We can measure frailty in an RCT cohort , and we believe that clinical trials should include more frail older people and that the use of an FI can facilitate such trials and generate reliable data to guide future medical practice in a rapidly ageing society CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , general 
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CONCLUSIONS The efficacy of pharmacologic treatments did not significantly differ , on average , between RCTs including older adults only and RCTs of all adults .