Trial Exclusion Criteria Research Articles

Decision Making in Lung Cancer – How Applicable are the Guidelines?

Modelling demand for radiotherapy is contingent on the uniform application of clinical practice guidelines. However, decision making in lung cancer is a complex process requiring the integration of multimodality treatment in patients who frequently have underlying comorbidities. Population studies have shown that guideline adherence in lung cancer is modest, ranging from 44 to 52%. The application of guideline treatment decreases with increasing age and the presence of comorbidities. Patient and clinician attitudes also impact on this. In some regions, sociodemographic factors, such as lower income and non-White race, have been associated with a lack of guideline treatment. One of the major barriers in treating lung cancer patients according to guidelines is the mismatch between the clinic population and those enrolled in clinical trials from which evidence is derived. The lung cancer clinic population often consists of patients who are older, have multiple comorbidities and are of borderline performance status, all characteristics that are usually exclusion criteria for clinical trials. Hence, there is uncertainty not only about the magnitude of benefit, but also potential toxicities of guideline treatment. Further research is necessary in order to define the best treatment in these patients and thus increase the applicability of guidelines to the general lung cancer population. Lung cancer is an extreme example of the difficulties in translating evidence into clinical practice. The applicability of guidelines to specific cancer populations will affect the modelling of demand for radiotherapy and other treatment modalities.

A polypeptide drug carrier for maternal delivery and prevention of fetal exposure

Background: Pregnant females are largely overlooked in drug development due to concerns for fetal health. Additionally, pregnancy is often an exclusion criterion in clinical trials, so the safety of many drugs during pregnancy is unknown.Purpose: The goal of this study was to evaluate Elastin-like Polypeptide (ELP), a synthetic protein derived from human elastin, for maternally sequestered drug delivery. ELP is a versatile drug carrier with a long plasma half-life, low immunogenicity, and the ability to be fused to nearly any small molecule or protein-based therapeutic.Methods: We determined the pharmacokinetics, biodistribution, and fetal exposure to the ELP drug carrier using quantitative fluorescence techniques in a rat pregnancy model.Results: After either bolus IV administration or continuous infusion over five days, ELPs accumulated strongly in the kidneys, liver, and placenta, but importantly, little to no ELPs were detectable in the fetus. Within the placenta, ELPs were localized to the chorionic plate and broadly distributed within the labyrinth, but were excluded from the fetal portion of the chorionic villi.Conclusion: These data indicate that ELP does not cross the placenta, and they suggest that this adaptable drug delivery system is a promising platform for prevention of fetal drug exposure.

Tools For Decision-Making In Older Cancer Patients. Role Of The Comprehensive Geriatric Assessment

Approximately 60% of cancer incidence and 70% of cancer mortality occurs in individuals older than 65 years. The optimal approach to cancer therapy in older adults is often unclear. Historically, advanced age has been an exclusion criterion in clinical cancer trials, and older adults have been consistently underrepresented. As a result, there is a lack of information about treatment efficacy and tolerability in this population. Comprehensive Geriatric Assessment (CGA) is one of the most useful tools for the oncologist to make decisions related to older patients diagnosed with cancer. This tool has proved to be very useful to detect many deficits, tolerance to chemotherapy and survival in such patients. In this review, we analyze the role of CGA in decision making in geriatric oncology.

TAVI with the self-expandable 29 mm core valve prosthesis in a patient with a metallic mitral valve

Transcatheter aortic valve implantation (TAVI) has been developed as a treatment solution to conventional open-heart surgery for patients with severe symptomatic aortic stenosis, but high perioperative risk. The history of mitral valve replacement was an exclusion criterion in the initial TAVI trials due to the risk of interference and subsequent functional impairment of the mechanical prosthesis. Such cases in the literature are rare, especially with the tube-like 55 mm long Medtronic CoreValve (MCV) prosthesis. We report a patient that underwent transfemoral TAVI using the MCV. The patient had undergone mechanical mitral valve replacement using a 23 mm St. Jude medical double tilting-disc prosthesis 20 years ago due to rheumatic mitral valve disease.

Why do GPs exclude patients from participating in research? An exploration of adherence to and divergence from trial criteria

The role of GPs in recruiting or excluding participants critically underpins the feasibility, external validity and generalizability of primary care research. A better understanding of this role is needed. To investigate why GPs excluded potentially eligible participants from a large scale randomized controlled trial (RCT), to determine the proportion of patients excluded on account of trial eligibility compared with other reasons, and to explore the impact of such exclusions on the management and generalizability of RCTs. Secondary analysis of data from the CoBalT study, a multi-centre general-practice-based RCT investigating cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression. GPs were asked to screen patient lists generated from computerized record searches for trial eligibility and to provide narrative reasons for excluding patients. These reasons were coded independently by two researchers, with a third researcher resolving discrepancies. Thirty-one percent (4750/15,379) of patients were excluded at the GP screening stage, including 663 on patient lists that remained unscreened. Of the 4087 actively excluded patients, 67% were excluded on account of trial exclusion criteria, 20% for other criteria (half of which were comorbid conditions) and 13% without reason. Clear, comprehensive criteria, particularly with regards to comorbidities, are required for GPs to confidently screen patients for potential participation in research. Future studies should promote inclusivity and encourage GPs to adopt a liberal approach when screening patient lists. This would enhance the validity and generalizability of primary care research and encourage greater patient autonomy.

Recruitment to trials of late thrombolysis: Lessons from the EXTEND study

To increase the percentage of acute stroke patients benefiting from thrombolysis, the utility of expanding the time window of treatment beyond 4.5hours after stroke onset needs to be investigated. We aimed to identify the target population and the challenges of recruitment of patients for the time window beyond 4.5hours. Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND), a multicentre randomised controlled trial testing the efficacy of thrombolytic therapy in patients with clinically significant ischaemic penumbra between 4.5 to 9hours after stroke onset, was used as a model to evaluate inclusion and exclusion criteria for late thrombolysis trials. Data from all stroke patients admitted to Austin Health over a 1year period were retrospectively analysed. Case notes were examined to determine potential trial eligibility. Of 556 patients assessed, 95 (17%) presented during the EXTEND time window. Sixty-seven of these (70.5%) were wake-up strokes (WUS) and 28 (29.5%) arrived between 4.5 and 9hours after symptoms onset. At least one exclusion criterion was found for 78 (82%) of them. Hence, 17 (3%) patients arrived within an appropriate time frame for the study without any exclusion criteria. Most of these (13) arrived outside routine MRI hours. The number of patients recruited would have increased more than three-fold if imaging had been available 24hours, 7days a week. A significant proportion (17%) of ischaemic stroke patients presented between 4.5 and 9hours after stroke onset. The majority of these were WUS. The major challenge identified for patient recruitment was imaging availability.

Prognostic factors for 60-day mortality in first-line treatment of metastatic colorectal cancer (mCRC): individual patient analysis of four randomised, controlled trials by the AIO colorectal cancer study group

BackgroundThe 60 day mortality is an established parameter for chemotherapy-related safety in randomised trials for metastatic colorectal cancer (mCRC). Prognostic factors associated with 60-day mortality would be helpful to identify high-risk patients in advance. Patients and methodsIndividual baseline patient data from four randomised, controlled trials from the Arbeitsgemeinschaft Internistische Onkologie (AIO) study group were retrospectively analysed. Chemotherapy consisted of fluoropyrimidine (5-FU/capecitabine), irinotecan, oxaliplatin with or without bevacizumab or cetuximab. Prognostic factors were identified by univariate and multivariate logistic regression models in two cohorts: one limited to ECOG PS 0 and 1 and one including ECOG PS 2 patients. ResultsA total of 1377 patients were evaluated. The analysis of ECOG PS 0, 1 and 2 patients consisted of 898 patients where a total of 33 deaths within the first 60 days of treatment (3.7%) occurred. In multivariate analysis, 60-day mortality was significantly associated with ECOG PS 2 and high leucocyte count (white blood cell, WBC). Odds ratio was 6.28 for WBC and 12.92 for ECOG PS 2. Exclusion of ECOG PS 2 patients but inclusion of one trial limited to ECOG PS 0 and 1 patients resulted in 1302 assessable patients and 44 early deaths (3.4%). In both cohorts, around 50% of deaths were disease related. WBC was confirmed as a significant risk factor for early death (OR 7.60). A combined score using ECOG PS 2 and WBC ≥8.000/µl is able to identify high-risk patients with a sensitivity of 18% and specificity of 98%. ConclusionsIn this large retrospective analysis of individual patient data, around 50% of early deaths were disease related. Elevated WBC was found strongly associated with increased 60-day mortality in first-line treatment of mCRC. The proposed AIO-60-Day-Mortality score serves as an additional trial exclusion criterion.

Representativeness of Patients Enrolled in Influential Clinical Trials: A Comparison of Substance Dependence With Other Medical Disorders

The purpose of this study was to determine whether randomized trials of treatments for substance dependence differ from those for other medical disorders on quality of enrollment information reporting and sample representativeness. Twenty highly cited clinical trials (publication date 2002-2010) of treatments for each of 14 prevalent disorders were identified by structured literature search. The disorders were alcohol dependence, drug dependence, nicotine dependence, Alzheimer's disease, breast cancer, colorectal cancer, chronic obstructive pulmonary disease, depression, diabetes, HIV/AIDS, hypertension, ischemic heart disease, lung cancer, and schizophrenia. The 280 clinical trials were coded for number of individuals screened for eligibility, number of screened individuals meeting eligibility criteria, and number of eligible individuals refusing to participate. Substance-dependence treatment trials were significantly more likely to track and report enrollment information (75% vs. 45% of clinical trials for other disorders, p < .001). Substance-dependence trials did not differ from trials focused on other disorders on mean rate of non-enrollment. Across disorders, the primary driver of non-enrollment appeared to be clinical trial exclusion criteria rather than eligible patients refusing to enroll. Relative to other disorders, trials in the substance-dependence field do a better (although imperfect) job of tracking and reporting enrollment information. Low enrollment rates and unrepresentative samples are not challenges unique to treatment outcome studies in the substance-dependence field. Across a range of disorders, clinical trials that use eligibility criteria judiciously are more likely to produce findings that generalize to front-line clinical practice than are trials that restrict enrollment to a small and unrepresentative subset of patients.

Analysis of docetaxel therapy in elderly (⩾70 years) castration resistant prostate cancer patients enrolled in the Netherlands Prostate Study

BackgroundProstate cancer truly is an age-associated disease. Due to the increased life expectancy and more sensitive diagnostic techniques in the Western world, prostate cancer is diagnosed more frequently and with rapidly increasing incidence and prevalence rates. However, age above 65 or 70years has been an exclusion criterion in clinical trials for decades and the knowledge about chemotherapy tolerance in elderly is limited. MethodsWe performed a retrospective analysis of data acquired from the recently published Netherlands Prostate Study (NePro) to evaluate the influence of advanced age on docetaxel therapy in elderly men (>70years) with castration resistant prostate cancer (CRPC) and bone metastases. Statistical analyses were performed stratified for age into four categories: <70 (n=315), 70–74 (n=150), 75–79 (n=85), and ⩾80years old (n=18). ResultsWe analysed 568 patients (median age 68.1years, range 46–89years, 44.5% aged ⩾70years). There was no relation between dosage and age (p=0.60). We found no significant differences between the number of dose reductions, time to progression (TTP), overall survival, chemotherapy tolerance and toxicity up to the age of 80years. However, when compared to younger men, men aged 80years or above more frequently experienced grade 3/4 toxicity and were five times less likely to complete the first three treatment cycles at the intended dose (Odds ratio (OR) 5.34, p=0.0052) and showed decreased overall survival (15.3months versus 24.5months in <80years group, p=0.020). ConclusionIn CRPC patients up to the age of 80years, docetaxel chemotherapy is well tolerated, with toxicity levels and TTP comparable to those of younger patients. For chemotherapeutic treatment of patients above the age of 80years an individual assessment should be made.

Analysis of docetaxel therapy in elderly (≥70yrs) castration resistant prostate cancer (CRPC) patients enrolled in the Netherlands Prostate Study (NePro).

e16059 Background: Prostate cancer truly is an age-associated disease, approximately half of prostate cancer patients in the Netherlands are aged 70 years or older at the time of diagnosis. However, age above 70 years has been an exclusion criterion in many clinical trials. Hence the knowledge about chemotherapy tolerance and toxicity in patients aged 70 years and above is limited. In this study we evaluated the influence of age on docetaxel chemotherapy in elderly (≥70yrs) castration resistant prostate cancer (CRPC) patients. Methods: Prostate cancer truly is an age-associated disease, approximately half of prostate cancer patients in the Netherlands are aged 70 years or older at the time of diagnosis. However, age above 70 years has been an exclusion criterion in many clinical trials. Hence the knowledge about chemotherapy tolerance and toxicity in patients aged 70 years and above is limited. In this study we evaluated the influence of age on docetaxel chemotherapy in elderly (≥70yrs) castration resistant prostate cancer (CRPC) patients. Results: We analyzed 568 patients (median age 68.1yrs, range 46-89yrs, 44.5% aged ≥70yrs). There was no relation between dosage and age (p=0.60). We found no significant differences between the number of dose reductions, TTP, overall survival, chemotherapy tolerance and toxicity up to the age of 80 years. However, when compared to younger men, men aged 80 years or above more frequently experienced grade 3/4 toxicity, were five times less likely to complete the first three treatment cycles at the intended dose (OR5.34, p=0.0052) and showed decreased overall survival (15.3mos versus 24.5mos in &lt;80yrs group, p=0.020). Conclusions: In mCRPC, and possibly other cancer patients, up to the age of 80 years docetaxel chemotherapy is well tolerated with toxicity levels, tolerance and TTP comparable to that of younger patients. However, for chemotherapeutic treatment of patients aged 80 years and above an individual assessment should be made.

Field practice studies on sorafenib: Lessons in systemic treatment of hepatocellular carcinoma

Since 2008 systemic therapy with Sorafenib became the tandard of care for patients with hepatocellular carcinoma (HCC) n the advanced (BCLC-C) or earlier stages (BCLC-B or -A), who were on-eligible or refractory to surgical or locoregional therapies [1]. vidence for this indication came from two registration trials, one un in Western countries and prematurely stopped for excess of enefit [2]. The question of whether the survival and safety findngs reported by the registration trials could be reproduced in real ife practice, where patients more often suffer from comorbidities nd may be significantly less fit than those matching the inclusion nd exclusion criteria of trials, was immediately raised. Given the thical unacceptability to run further placebo-controlled randomzed trials at present, such information could come only from field ractice studies. Indeed, the regulatory agencies requested obserational data from clinical practice to confirm safety, corresponding o the still unpublished worldwide GIDEON study (NCT00812175). hile awaiting for the results of this huge dataset to be released, arious smaller field practice study investigated efficacy of HCC reatment with Sorafenib. The study by Woerms and coworkers published in the present ssue of Digestive and Liver Disease [3] reports a single centre large xperience of consecutive patients treated with Sorafenib for HCC. hen considering the group of patients with a condition similar o those included in the registration trials (Child-Pugh A, most in dvanced stage), overall survival in real life (10.5 months) was pracically superimposable to that reported in the Western registration rial (10.7 months) [2] and in line with a few other studies, includng a couple of recent large Italian multicenter experiences (293 atients, 88% Child-Pugh A patients, 10.5 months; [4] 116 patients, 3% in Child-Pugh A, 13.0 months) [5]. Not only was overall surival almost superimposable in German and Italian field practice ata for Child-Pugh A patients; also the time on Sorafenib treatment respectively 4.0 and 4.2 months) when reported, was similar [3,4]. espite such confirmations highlight the overall beneficial role of orafenib, it is also well known from daily clinical experience, that ome patients benefit enormously from treatment with Sorafenib,

Hospitalized patients with atrial fibrillation compared to those included in recent trials on novel oral anticoagulants: A population-based study

BackgroundNonvalvular atrial fibrillation is associated with a substantial risk of stroke. Novel oral anticoagulants (NOACs) with predictable anticoagulant effect and no need for routine coagulation monitoring have recently shown good results when compared with warfarin in phase III clinical trials. ObjectiveTo describe clinical features and pharmacological treatments of a population-based cohort of patients with nonvalvular atrial fibrillation and ascertain whether they are comparable with those included in the three main phase III clinical trials on NOACs. ResultsOf the 2,862,264 subjects considered for this study 13,360 patients (0.47%) were recently discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation. Mean age was 76.3 (SD 10.7), 49.8% were men and 64.6% were ≥75years of age. 50% of patients were treated with warfarin and 44.1% with antiplatelet agents. The proportion of patients on antiplatelet therapy increased with age up to a rate of 54.3% in subjects ≥85years. 92.9% of the studied cohort was on polypharmacy (mean 8 drugs/patient). Around 20% of the entire cohort was treated with amiodarone, a drug potentially interfering with NOACs, and 3.6% from a subgroup analysis had renal failure, which is an exclusion criterion in trials on NOACs. ConclusionIn patients recently discharged from the hospital with the diagnosis of nonvalvular AF, warfarin use decreases and aspirin treatment increases with patients' age. These patients are older, more frequently female, and on multiple medications. The benefit of NOACs in these subjects needs to be confirmed in phase IV clinical studies.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Adherence of non-pharmaceutically sponsored oncology trial protocols to the International Conference on Harmonization (ICH) guidelines in an academic institution outside the ICH jurisdictions and the impact of IRB implementation on this adherence

PurposeTo assess adherence of non-pharmaceutically sponsored trials (non-PSTs) to ICH protocol structure guidelines and to estimate the effect of implementing Institutional Review Board’s (IRB) review on this adherence. MethodsThis is a retrospective exploratory study where 60 non-PST clinical trial protocols (CTPs) were reviewed and halved to IRB-reviewed CTPs (IRCTPs) and non-IRB-reviewed CTPs (non-IRCTPs). Adherence score (AS) was calculated as the number of fulfilled items or sub-items divided by their total number. ResultsThree adherence patterns were encountered: (1) items consistently present in both groups e.g. general and background information, objectives, inclusion criteria and intervention details, (2) items consistently absent in both groups and included contact information of investigators and trial sites, product accountability, randomization codes’ management, interim analyses and many other statistical aspects, and (3) items variably present in both groups where the effect of IRB was verifiable. Trial site details, potential benefits, discontinuation and exclusion criteria, and follow up for adverse events were more encountered in IRCTPs than non-IRCTPs. Withdrawal criteria and monitoring of treatment compliance showed a reverse pattern (p<0.05 for all). The total AS, administrative AS and ethics AS for IRCTPs was 43%, 22% and 70% compared to 38%, 16% and 33% for non-IRCTPs (p<0.003, <0.001, 0.004), respectively. The scientific AS was 54% for both groups (p=0.87). ConclusionsIRB-implementation at NCI-Egypt improved ethical and administrative sections of academic protocols. However, this improvement is modest and needs further actions including adoption of protocol templates. Scientific sections were as good after IRB-implementation as they were before that.

How to generalize efficacy results of randomized trials: recommendations based on a systematic review of possible approaches

Randomized controlled trials (RCTs) are the preferred source for evidence for the effect of treatment. However, patients participating in RCTs often manifest important differences from patients seen in practice. Therefore, guideline developers have to decide whether the results are generalizable to the target population not represented in RCTs. A systematic review of the literature was undertaken to identify methods to decide whether to generalize the results from RCTs to patients who were not represented in these trials. One approach is to examine the in- and exclusion criteria of trials and infer from these whether the trial population was sufficiently representative. Other authors suggest, because of the inclusion of a broader range of patients, reliance on observational studies if no direct evidence for the target population is available. Another approach is to apply the relative effect of treatment found in trials to patients in practice unless there is a compelling reason to believe the results would differ substantially as a function of particular characteristics of those patients. Although there are exceptions, this approach is supported by empirical evidence that, in general, relative effect of treatment on benefit outcomes seldom differs to an important extent across subgroups of patients. We propose this last approach: focusing on RCTs unless there is a compelling reason not to do so. Compelling reasons will most often be found with respect to issues of rare adverse effects, for which observational studies are likely to provide the best estimates.

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles. A Cochrane review †

Several systematic reviews compared recombinant gonadotrophin with urinary gonadotrophins (HMG, purified FSH and highly purified FSH) for ovarian hyperstimulation in IVF and ICSI cycles and these reported conflicting results. Each of these reviews used different inclusion and exclusion criteria for trials. Our aim in producing this review was to bring together all randomized studies in this field under common inclusion criteria with consistent and valid statistical methods.

Methods report on the development of the European S3 guidelines for the treatment of acne

Methods report on the development of the European S3 guidelines for the treatment of acne

Safety and Outcomes following Thrombolytic Treatment in Stroke Patients Who Had Received Prior Treatment with Anticoagulants

Background: Information is scare regarding the safety of intravenous thrombolysis in patients under anticoagulant treatment, given that this is an exclusion criterion in clinical trials. We analyzed the risk of hemorrhagic complications following thrombolysis in patients under treatment with low-molecular-weight heparins (LMWH) and oral anticoagulants (OA). Methods: In a multicentered prospective study of consecutive acute stroke patients treated with intravenous alteplase we recorded age, gender, baseline NIHSS score, treatment delay, risk factors, etiology and previous therapy. The neurological progress (National Institutes of Health Stroke Scale at 7 days) and functional evolution at 3 months (modified Rankin Scale score), mortality and symptomatic intracerebral hemorrhage (SICH) were compared between patients with LMWH or OA and those without prior anticoagulant therapy. Results: Of the 1,482 patients, 21 (1.4%) had received LMWH and 70 (4.7%) OA (international normalized ratio, INR, 0.9-2.0). Patients on OA were older, presented higher basal glucose levels, had been treated later and had a higher prevalence of hypertension, dyslipidemia, prior stroke, atrial fibrillation and cardioembolic pathologies. The severity of stroke on admission was similar in the different groups. The percentages of patients achieving independence (mRS 0-2) at 3 months were 33, 44 and 58 (LMWH, OA and no prior anticoagulant treatment, respectively; p = 0.02 for both comparisons of LMWH vs. no treatment and OA vs. no treatment); the mortality rates were 30, 25 and 12% (p = 0.010, p = 0.001, respectively) and the SICH were 14, 3 and 2% (p < 0.0001 for comparison of LMWH vs. no treatment). In the case of treatment with OA, the outcomes were independent of the INR value. Following adjustment for confounding variables, the prior use of OA was associated with higher mortality (OR: 2.15, 95% CI: 1.1-4.2; p = 0.026) but not with SICH transformation or lower probability of independence. The use of LMWH was associated with higher mortality (OR: 5.3, 95% CI: 1.8-15.5; p = 0.002), risk of SICH (OR: 8.4, 95% CI: 2.2-32.2; p = 0.002) and lower probability of achieving independence (OR: 0.3, 95% CI: 0.1-0.97; p = 0.043). Conclusions: The use of intravenous thrombolysis appears to be safe in patients previously treated with OA with INR levels <2 since there is no increase in SICH. The prior use of LMWH appears to increase the risk of SICH, death and dependence and, as such, the decision for systemic treatment with thrombolytic agents needs to be taken with caution in these cases. Larger case series are necessary to confirm these findings.

Transcatheter aortic valve implantation in bicuspid aortic valve: never say never

Transcatheter aortic valve implantation (TAVI) is an emerging alternative technique that has shown promise in the treatment of severe aortic stenosis in patient populations at high risk with conventional surgery. The presence of a bicuspid aortic valve (BAV) has been considered an exclusion criterion for TAVI, because of the presumed risk for poor seating or paravalvular regurgitation due to severe distortion of the native valve leaflets. For this reason, BAV disease has generally been an exclusion criterion in major trials of TAVI and there is little clinical experience available. We report a case of transcatheter valve replacement in a poor surgical candidate with BAV stenosis using a new 29 mm Edwards Sapien prosthesis.

Impact of renal dysfunction on the prognostic value of the TIMI risk score in patients with non-ST elevation acute coronary syndrome

The thrombolysis-in-myocardial-infarction risk score (TRS) is a validated risk-assessment tool based on randomized clinical trials. Its applicability to an unselected group of patients seen in general clinical practice may be limited as renal dysfunction was an exclusion criteria in the original trials upon which the TRS was determined. Consecutive patients with non-ST elevation acute coronary syndrome were stratified based on renal function. Normal renal function was defined as a creatinine clearance (CrCl) of more than 60 ml/min, moderate renal dysfunction was defined as a CrCl of at least 30 ml/min but 60 ml/min or less, and severe renal dysfunction was defined as a CrCl of less than 30 ml/min. A TRS was calculated using the original seven criteria (TRS-7) which did not consider renal function. A second TRS was calculated using the original seven criteria plus the addition of renal dysfunction if the CrCl was 60 ml/min or less (TRS-8 ≤ 60). A third TRS was calculated using the original seven criteria plus renal dysfunction if the CrCl was less than 30 ml/min (TRS-8<30). In the calculation of both of the TRS-8, the presence of renal dysfunction was given weight equal to each of the original seven criteria. Comparisons between groups stratified by renal function were made using Pearson's χ² test or Fisher's exact test for categorical variables (presented as counts and percentages) and the unpaired t-test for continuous variables (presented as the mean ± standard deviation). The χ² test was used to compare the statistical differences between each of the three TRS and the percentage of patients achieving the primary composite outcome during the index hospitalization. The primary outcome was the composite of cardiovascular death, nonfatal myocardial infarction, or urgent coronary revascularization for documented myocardial ischemia. Of the 798 patients included in the analysis, 281 (35%) patients had renal dysfunction (26% had moderate dysfunction and 9% had severe dysfunction). When considered categorically, patients with moderate or severe renal dysfunction had significantly higher rates of the primary composite outcome. The three TRS (TRS-7, TRS-8 ≤ 60, and TRS-8<30) were significantly correlated with the primary composite outcome. With a calculated TRS of 5 or less, the TRS-8 ≤ 60 and the TRS<30 were not associated with a significantly higher prevalence of the composite outcome (all comparisons P>0.05). At a calculated TRS of 6 or 7, the TRS-8<30 was associated with a significantly greater prevalence of the composite outcome compared with the TRS-7 (P=0.02) and the TRS-8 ≤ 60 (P=0.02). There was no significant difference in the frequency of the composite outcome with a calculated TRS of 6 or 7 using the TRS-7 compared with the TRS-8 ≤ 60 (P=0.79). At a calculated TRS of 8, both the TRS-8<30 and TRS-8 ≤ 60 had a significantly higher prevalence of the composite outcome compared with a calculated TRS of 7 using the TRS-7 (P=0.002 for the TRS-8<30 and P=0.045 for the TRS-8 ≤ 60). At a TRS of 8, the TRS-8<30 was associated with a significantly higher composite outcome compared with the TRS-8 ≤ 60 (P=0.035). The addition of renal dysfunction to the TRS-7 as an eighth clinical criterion was associated with a higher prevalence of the primary composite outcome primarily at scores of 6 or more. When considered in the context of clinical practice, the use of the TRS-8 ≤ 60 and TRS-8<30 rather than the TRS-7 would not be expected to substantially change the management strategy for patients presenting with non-ST elevation acute coronary syndrome.