A sequential enriched design for target patient population in psychiatric clinical trials

2014 ◽  
Vol 33 (17) ◽  
pp. 2953-2967 ◽  
Author(s):  
Yeh-Fong Chen ◽  
Xiangmin Zhang ◽  
Roy N. Tamura ◽  
Chiung M. Chen
Keyword(s):  
Clinical Trials ◽  
Patient Population ◽  
Target Patient Population

scholarly journals Is there a role for adjuvant therapy after surgery in “high risk for recurrence” kidney cancer? An update on current concepts

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
T. Sharma ◽  
C. Tajzler ◽  
A. Kapoor
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Patient Population ◽  
Treatment Options ◽  
Significant Proportion ◽  
High Risk Patient ◽  
Disease Free Survival ◽  
Cochrane Reviews

BackgroundAlthough surgical resection remains the standard of care for localized kidney cancers, a significant proportion of patients experience systemic recurrence after surgery and hence might benefit from effective adjuvant therapy. So far, several treatment options have been evaluated in adjuvant clinical trials, but only a few have provided promising results. Nevertheless, with the recent development of targeted therapy and immunomodulatory therapy, a series of clinical trials are in progress to evaluate the potential of those novel agents in the adjuvant setting. In this paper, we provide a narrative review of the progress in this field, and we summarize the results from recent adjuvant trials that have been completed.MethodsA literature search was conducted. The primary search strategy at the medline, Cochrane reviews, and http://ClinicalTrials.gov/ databases included the keywords “adjuvant therapy,” “renal cell carcinoma,” and “targeted therapy or/and immunotherapy.”ConclusionsData from the s-trac study indicated that, in the “highest risk for recurrence” patient population, disease-free survival was increased with the use of adjuvant sunitinib compared with placebo. The assure trial showed no benefit for adjuvant sunitinib or sorafenib in the “intermediate- to high-risk” patient population. The ariser (adjuvant girentuximab) and protect (adjuvant pazopanib) trials indicated no survival benefit, but subgroup analyses in both trials recommended further investigation. The inconsistency in some of the current results can be attributed to a variety of factors pertaining to the lack of standardization across the trials. Nevertheless, patients in the “high risk of recurrence” category after surgery for their disease would benefit from a discussion about the potential benefits of adjuvant treatment and enrolment in ongoing adjuvant trials.

scholarly journals Heterogeneity of Recent Phase 3 Complicated Urinary Tract Infection Clinical Trials

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Simon Portsmouth ◽  
Almasa Bass ◽  
Roger Echols ◽  
Glenn Tillotson
Keyword(s):  
Clinical Trials ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Study Design ◽  
Patient Population ◽  
Complicated Urinary Tract Infection ◽  
Gram Negative ◽  
Regulatory Guidelines ◽  
New Antibiotics

Abstract Background For new antibiotics developed to treat antibiotic-resistant Gram-negative infections, the US Food and Drug Administration (FDA) regulatory pathway includes complicated urinary tract infection (cUTI) clinical trials in which the clinical isolates are susceptible to the active control. This allows for inferential testing in a noninferiority study design. Although complying with regulatory guidelines, individual clinical trials may differ substantially in design and patient population. To determine variables that impacted patient selection and outcome parameters, 6 recent cUTI trials that were pivotal to an new drug application (NDA) submission were reviewed. Methods This selective descriptive analysis utilized cUTI trial data, obtained from publicly disclosed information including FDA documents and peer-reviewed publications, from 6 new antibiotics developed to treat multidrug-resistant Gram-negative infections: ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol, plazomicin, and fosfomycin. Eravacycline was not approved for cUTI and is not included. Results Microbiologic modified intent-to-treat sample size, age, proportions of female patients, acute pyelonephritis (AP), Escherichia coli and other pathogens at baseline, protocol-specified switch to oral antibiotic, and the noninferiority margin were compared. Outcome data included clinical response, microbiologic eradication, and composite outcomes, including a subset of patients with AP. Conclusions A study design can follow regulatory guidelines but still have variable populations. The proportion of AP within a study varied greatly and influenced population demographics (age, gender) and baseline microbiology. A smaller proportion of AP resulted in an older patient population, fewer females, less E coli, and lower proportions of patients achieving success. Fluoroquinolones and piperacillin/tazobactam should be reconsidered as active comparators given the high rates of resistance to these antibiotics.

scholarly journals Evolution of psoriatic arthritis study patient population characteristics in the era of biological treatments

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000779 ◽  
Author(s):  
Ann-Sophie Vandendorpe ◽  
Kurt de Vlam ◽  
Rik Lories
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Patient Population ◽  
Patient Characteristics ◽  
Chronic Inflammatory Disease ◽  
Population Characteristics ◽  
Phase Iii ◽  
Study Patient

ObjectivesPsoriatic arthritis is a chronic inflammatory disease that affects the musculoskeletal system. It can include arthritis, spondylitis, dactylitis and enthesitis, and is strongly associated with the presence of psoriasis. The introduction of biological therapies as a treatment option has brought a significant improvement in disease control for patients with psoriatic arthritis. Here, we aimed to detect emerging differences in demographic and clinical characteristics of the psoriatic arthritis patient study population since the introduction of biologicals. We hypothesised that evolving views on control of disease activity and increased experience in the management of psoriatic arthritis have affected the patient population considered for clinical trials and that this may serve as a proxy for changes in clinical practice.MethodsWe systematically searched for and selected 12 phase II and phase III trials and divided them into three treatment periods based on different time periods and working mechanisms of the particular biologicals. We made a selection of patient and disease parameters for which data were available in all three periods, calculated those data per period and looked for statistically significant differences between the treatment periods.ResultsStatistical analysis showed significant differences in patient characteristics, disease characteristics, disease activity, disease effects and use of prior treatments between the patient populations of the three periods.ConclusionThis study shows a clear evolution of the patient population considered for clinical trials since the introduction of biologicals. Further research is needed to see if those changes can be detected in the daily clinical practice.

Molecular prescreening to select patient population in early clinical trials

2012 ◽  
Vol 9 (6) ◽  
pp. 359-366 ◽  
Author(s):  
Jordi Rodón ◽  
Cristina Saura ◽  
Rodrigo Dienstmann ◽  
Ana Vivancos ◽  
Santiago Ramón y Cajal ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Patient Population ◽  
Select Patient

Fluconazole and Amphotericin B for Cryptococcal Meningitis

1996 ◽  
Vol 30 (12) ◽  
pp. 1408-1410 ◽  
Author(s):  
Amy B Clark ◽  
Bob L Lobo ◽  
Michael S Gelfand
Keyword(s):  
Clinical Trials ◽  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Patient Population ◽  
Standard Therapy ◽  
Alternative Therapy ◽  
Poor Response ◽  
Case Summary

OBJECTIVE: To describe a patient with cryptococcal meningitis treated with the combination of amphotericin B and fluconazole. CASE SUMMARY: A 41-year-old woman with cryptococcal meningitis who was not infected with HIV was treated with a combination of amphotericin B and fluconazole because she did not respond to amphotericin B alone and could not tolerate amphotericin B with flucytosine. She improved clinically, but it is unclear whether the combination was beneficial. DISCUSSION: Standard therapy for cryptococcal meningitis is amphotericin B with or without flucytosine. Fluconazole is an alternative therapy, but its efficacy has not been documented in the patient population not infected with HIV. Theoretically, the combination of amphotericin B and fluconazole is antagonistic, but in vitro and in vivo data suggest that antagonism may not occur. The combination of amphotericin B and fluconazole in cryptococcal meningitis has not been evaluated in clinical trials, and its use is not recommended. CONCLUSIONS: A patient with cryptococcal meningitis was treated with the combination of amphotericin B and fluconazole because of a poor response to amphotericin B monotherapy and intolerance to flucytosine. It is unclear whether her clinical response was a result of the combination.

Efficacy of Yttrium-90 Zevalin Outside of Clinical Trials: Preliminary Results of a Retrospective Bi-Center Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5015-5015
Author(s):  
Francesco Cicone ◽  
Francesco Scopinaro ◽  
Sebastien Baechler ◽  
Nicolas Ketterer ◽  
Franz Buchegger ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Setting ◽  
Patient Population ◽  
Statistical Significance ◽  
University Hospital ◽  
Low Grade ◽  
Number Of Patients ◽  
Significant Difference ◽  
Routine Clinical Setting

Abstract Background and Aim: Due to limited data regarding the efficacy of Radioimmunotherapy with 90Y-Zevalin (RIT-Z) outside of controlled clinical trials, we carried out a biinstitutional, international retrospective study to assess the efficacy of RIT-Z in a routine clinical setting. The relationship between the number of previous therapies and outcomes as well as the response to the last therapy was assessed. Possible differences in outcomes for patients treated in the two different centers were also analyzed. Materials and Methods: Forty-three consecutive patients treated at the University Hospital of Lausanne (CHUV, Switzerland) and at S. Andrea University Hospital of Rome (Italy) were evaluated, none of which had been previously included in clinical trials. Only 31 patients entered the final analysis: patients lost at follow up, undergoing autologous transplantation (ASCT), or treated within the last 3 months were excluded. Efficacy of therapy was evaluated in terms of Overall Survival (OS), Progression Free Survival (PFS), and Time to Next Treatment (TTNT). Survival curves were obtained with the Kaplan- Meier method (statistical significance = p<0.05). Results: Characteristics of the patient population are listed in Table 1. Although 50% of the patients had aggressive histologies, patients treated at S. Andrea had slightly more favorable features than those treated at CHUV. Fourteen patients (45%) had received at least 4 previous treatments, and all had received Rituximab. Fourteen patients (45%) had not responded to the last therapy, while 6 (19%), all treated at S.Andrea, were considered disease-free at the time of RIT-Z, which was administered for consolidation. Median follow up time was 20 months (11.5 vs. 25 months for S.Andrea and CHUV, respectively). Median PFS and TTNT were similar. After achieving a partial response, 2 patients were referred to Rituximab maintenance after RIT-Z and remain progression-free. Median OS was still not attained. Although not statistically significant, a trend towards better outcomes for S. Andrea patients was found. In comparing patients with indolent and aggressive lymphoma, only PFS was found to be significantly different (median PFS: 10 vs. 5 months, p<0.05). In patients with <4 and ≥ 4 previous therapies, twenty month OS was 88% vs. 53.6% (p=0.02), respectively; median TTNT was 22 vs. 5 months (p=0.013), while differences in PFS did not attain statistical significance. The duration of response in non-responders to their last therapy was shorter than in responders: 20-month OS- 44% vs. 94% (p=0.0015), median PFS and TTNT- 3.5 vs. 15 months (p=0.0002) and 4 vs. 15 months (p=0.0001), respectively. Median PFS and TTNT after RIT-Z did not differ from those found after the last therapy. A significant difference in outcomes for heavily pretreated or refractory patients was found in those with low grade follicular lymphoma. Conclusions: Poorer outcomes were found in our patient population treated in a routine clinical setting compared to those enrolled in clinical trials. This may be related to greater heterogeneity of our study cohort which included more patients with unfavorable conditions (e.g. aggressive NHL, ≥4 treatment courses including rituximab in all, and ASCT in 25%). Our results suggest that the best benefit may be expected with RIT-Z either for consolidation or relatively earlier in the course of NHL treatment. Table 1. Total CHUV S. Andrea Population Analyzed (72%) Number of patients 43 23 20 31 Median Age 61 63 58,5 62 Aggressive Histology (FL grade 3 or DLBCL) 18 (41,8%) 8 (34,7%) 10 (50%) 11 (35,5%) Indolent Histology (FL grade 1 or 2) (%) 25 (58,2%) 15 (65,3%) 10 (50%) 20 (64,5%) Patients with ≥4 previous treatments 19 (44,2%) 12 (52,1%) 7 (35%) 14 (45,2%) Patients with previous ASCT 11 (25,6%) 6 (26%) 5 (25%) 8 (25%)

Ineligibility of prostate cancer patients in the VA Connecticut Healthcare System (VACHS) to participate in clinical trials due to comorbidities

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5169-5169
Author(s):  
T. M. Mayer ◽  
W. K. Kelly ◽  
J. Concato ◽  
H. Chao
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Healthcare System ◽  
Patient Population ◽  
Performance Status ◽  
Phase Iii ◽  
Medical Conditions ◽  
Eligibility Criteria ◽  
Major Phase

5169 Background: A large proportion of prostate cancer patients receive their care within the VA Healthcare System. As this is a population affected by complex comorbidities, they may be underrepresented in oncology clinical trials. Our objective was to quantify the frequency with which castrate resistant prostate cancer (CRPC) patients in VACHS would be excluded from major phase III randomized controlled trials. Methods: We reviewed records of all prostate cancer patients at the VACHS between 2004–2007 and identified patients with CRPC. We reviewed eligibility criteria of 24 major phase III clinical trials, from 2006 onwards, studying investigational drugs for CRPC and created a “master list” (ML) of the most pertinent criteria. We analyzed our patient population according to both the ML criteria and to the TAX327 study criteria. Results: We identified 106 patients with CRPC, excluded 7 patients with insufficient medical records, and analyzed 99 patients. Performance status and life expectancy could not be accurately assessed from most charts and were excluded as specific criteria (though reflected in other serious medical condition). Major reasons for exclusion according to ML/TAX327 criteria include: 10/10 other malignancy within 5 years; 11/14 abnormal laboratory parameters; 27/30 other serious medical conditions; 3/4 abnormal cardiac function. ML list only exclusions: 5 active angina; 1 unstable DM; 1 major GI surgery; 1 contraindication to steroids. Serious medical conditions included: active cardiac disease, dementia, serious neurologic, psychiatric, vascular, pulmonary or hematologic disease, and poor performance status or compliance. Overall, 45% (45/99) of patients were excluded when using both the ML and TAX327 criteria. Conclusions: Approximately half of CRPC patients in the VACHS between 2004–2007 did not meet eligibility criteria for major therapeutic trials for CRPC. This retrospective review demonstrates that VA patients are underrepresented in randomized clinical trials for CRPC and are a special population due to their complex comorbidities. These findings underscore the importance of designing better clinical trials for CRPC with less barriers for this underrepresented but common patient population. No significant financial relationships to disclose.

Clinical trial feasibility assessment and start-up tool (CTFAST).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14089-e14089
Author(s):  
Amanda Tice ◽  
Richard Dima ◽  
Wasif M. Saif ◽  
Melissa Panzo ◽  
Sarah R. Vaiselbuh
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Patient Population ◽  
Feasibility Analysis ◽  
Pharmacokinetic Studies ◽  
Research Experience ◽  
Team Members ◽  
Feasibility Assessment ◽  
Start Up ◽  
The Right

e14089 Background: Selecting the right clinical trials for patients remains a challenging job. The better the match between a clinical trial and the target patient population before conducting a study, the more likely the study will successfully reach the target goal of recruitment. We developed a feasibility assessment scoring system based on our vast clinical research experience, managing multiple sites across a large health system, applicable to oncology as well. Methods: Our feasibility team (FT) is responsible for identifying clinical trials and determining if they are an appropriate match for our institution and unique patient population. Once a potential trial is identified, FT performs a feasibility assessment of the research protocol to determine the resources required to conduct the trial. We developed a Clinical Trial Feasibility Assessment & Start-up Tool (CTFAST) to help sites streamline their feasibility assessments and track their trial through the start-up phase. With CTFAST a feasibility score is generated based on the cumulative value assigned to several items such as: sponsor, study type, pharmacokinetic studies, trial phase, etc. A feasibility scale is assigned as follows: > 25 – Accepted; 15-25 – On Hold; < 15- Rejected. Accepted studies are assigned a color coded priority track (fast, intermediate, routine), that allows team members to prioritize their studies accordingly. Once a study is accepted, the study is processed for enrollment. Results: CTFAST has increased productivity and clinical trial revenues by 40%. CTFAST allows for early identification of bottlenecks in workflow, thereby improving outcomes. By appropriately matching of clinical trials to our site, enrollments increased by 50% with an expanded clinical trial portfolio across 9 different departments. Study start-up times have been reduced to a minimum of 21 days and the use of time & effort has been optimized. Conclusions: CTFAST is replicable across all clinical trial sites and provides an expansive and critical feasibility analysis that is not attainable by traditional querying of investigators and questionnaires. It is an excellent work flow improvement tool as it critically analyzes all aspects of a study, prior to enrollment. When conducting an effective feasibility analysis the clinical trial site can optimize clinical trial outcomes.

Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group

2013 ◽  
Vol 14 (10) ◽  
pp. e396-e406 ◽  
Author(s):  
Nancy U Lin ◽  
Eudocia Q Lee ◽  
Hidefumi Aoyama ◽  
Igor J Barani ◽  
Brigitta G Baumert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Metastases ◽  
Patient Population ◽  
Solid Tumour ◽  
Population Response
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