Clinical Trials in Schizophrenia with Results for the Real World

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S7) ◽  
pp. 9-13 ◽  
Author(s):  
Diana O. Perkins

AbstractMost clinical data for antipsychotics come from studies designed to test the efficacy and safety of the drugs under ideal conditions, in limited subgroups of patients. In contrast, practical clinical trials (PCTs) are designed to test the effectiveness of different treatment options under conditions that more accurately reflect actual clinical practice. Consequently, PCTs are able to provide information that can be utilized by healthcare providers and other decision makers. Characteristics of PCTs include a clinically relevant question, a representative sample of patients and practice settings, sufficient power to identify modest relevant effects, randomization to protect against bias, uncertainty regarding the outcome of treatment, assessment and treatment protocols that enact best clinical practices, simple and relevant outcomes, and limited subject and investigator burden. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) research program is an example of a PCT. The CATIE study illustrates how PCTs, when properly designed, might be helpful in informing clinical decision making. Because the CATIE study was designed to reflect the effectiveness of antipsychotics under naturalistic clinical conditions, its results should have particular applicability to the arena of clinical practice. This article provides a discussion of the differences between efficacy and effectiveness studies. In assessing the practical utility of results from the CATIE study, much can be learned on how to shape future studies of effectiveness so as to better generate data that are applicable to the “real world.”

2020 ◽  
Vol 14 ◽  
pp. 117954682095341 ◽  
Author(s):  
Todd C Villines ◽  
Mark J Cziraky ◽  
Alpesh N Amin

Real-world evidence (RWE) provides a potential rich source of additional information to the body of data available from randomized clinical trials (RCTs), but there is a need to understand the strengths and limitations of RWE before it can be applied to clinical practice. To gain insight into current thinking in clinical decision making and utility of different data sources, a representative sampling of US cardiologists selected from the current, active Fellows of the American College of Cardiology (ACC) were surveyed to evaluate their perceptions of findings from RCTs and RWE studies and their application in clinical practice. The survey was conducted online via the ACC web portal between 12 July and 11 August 2017. Of the 548 active ACC Fellows invited as panel members, 173 completed the survey (32% response), most of whom were board certified in general cardiology (n = 119, 69%) or interventional cardiology (n = 40, 23%). The survey results indicated a wide range of familiarity with and utilization of RWE amongst cardiologists. Most cardiologists were familiar with RWE and considered RWE in clinical practice at least some of the time. However, a significant minority of survey respondents had rarely or never applied RWE learnings in their clinical practice, and many did not feel confident in the results of RWE other than registry data. These survey findings suggest that additional education on how to assess and interpret RWE could help physicians to integrate data and learnings from RCTs and RWE to best guide clinical decision making.


2021 ◽  
Vol 15 (1) ◽  
pp. 5-21
Author(s):  
D. P. Kamilova ◽  
M. M. Ovchinnikova ◽  
E. Sh. Ablyaeva ◽  
M. M. Leviashvili ◽  
N. S. Stuleva ◽  
...  

Introduction. The efficacy and safety of biosimilar follitropin alpha have been demonstrated in randomized blinded prospective clinical trials of phases I and III. Unfortunately, there is a gap between the clinical trials and real clinical practice data. The real-world patient data helps to create an evidence-based background for successful implementation of medicine at everyday practice in a nonselected population.Aim: to investigate the efficacy of follitropin alpha biosimilar therapy (Primapur®) in nonselected real-world population.Materials and Methods. A retrospective observational anonymized cohort study of follitropin alpha biosimilar (Primapur®) as a pre-filled pen injector with a dose adjustment of 5 IU, aimed to investigate its efficacy and safety in a nonselected population with indications to assisted reproductive technologies (ART) was carried out. The ovarian stimulation (OS) protocols included: monotherapy protocols with using only Primapur®; mixed protocols (recombinant and urinary-derived gonadotropins); short protocols with using antagonists of gonadotropin-releasing hormone (GnRH) and long protocols with GnRH agonists. The stimulation protocols were analyzed with Primapur® application for at least 5 days.Results. The overall clinical efficacy of ovarian stimulation cycles (N = 5484) was: oocytes retrieved - 9.5 ± 7.2, mature (MII) - 6.8 ± 6.6, fertilized (2PN) - 6.1 ± 5.8, clinical pregnancy per ET (PR) - 38.4 %. Mixed gonadotropin protocols (N = 2625) vs. monotherapy with Primapur® (N = 2859): oocytes retrieved - 8.6 ± 6.8 vs. 10.3 ± 7.4 (p < 0.001), mature (MII) - 6.7 ± 6.2 vs. 7.7 ± 6.9 (p < 0.001), fertilized (2PN) - 5.8 ± 5.2 vs. 7.2 ± 6.2 (p < 0.001). There were statistically significant differences between oocyte yields in mixed vs. monotherapy protocols due to subgroup differences, including age, body mass index (BMI) and IVF/ICSI attempts. No statistically significant differences were found for PR: 39.3 % vs. 37.6 % (p = 0.314). Monotherapy protocols with GnRH antagonist OS (N = 2183) vs. GnRH agonist (N = 676) revealed: oocytes retrieved - 10.5 ± 7.5 vs. 9.6 ± 7.0 (p = 0.032), mature (MII) - 7.6 ± 6.9 vs. 6.7 ± 5.7 (p < 0.001), fertilized (2PN) - 7.3 ± 6.3 vs. 5.7 ± 5.0 (p < 0.001). There were statistically significant differences between BMI and IVF/ICSI attempts. No statistically significant differences were found for PR: 37.9 % vs. 35.9 % (p = 0.482). All medicines were well tolerated and no serious adverse reactions were reported.Conclusion. This was the largest retrospective observational study conducted in the field of fertility in Russia and involved 5484 ovarian stimulation protocols at 35 IVF clinics. The obtained results demonstrated similar clinical efficacy for follitropin alpha biosimilar Primapur® in different OS protocols in real clinical practice. 


2020 ◽  
Vol 24 (5) ◽  
pp. 468-473
Author(s):  
Christine E. Jo ◽  
Jorge R. Georgakopoulos ◽  
Matthew Ladda ◽  
Arvin Ighani ◽  
Asfandyar Mufti ◽  
...  

Background Systemic therapy for atopic dermatitis (AD) has been challenging with limited safe and efficacious long-term treatment options. In 2017, dupilumab was approved in the United States, Europe, and Canada as the first targeted therapy for patients with moderate-to-severe AD. Despite promising efficacy and safety results in clinical trials, our understanding of dupilumab in clinical practice remains limited with few studies outside clinical trials in literature. Objective The aim of this study is to evaluate the efficacy and safety of dupilumab in clinical practice and discuss any differences in results between clinical trials and real-world results. Methods A retrospective chart review was conducted of consecutive patients receiving dupilumab treatment at two tertiary hospitals in Toronto, Canada, between December 2017 and May 2019. The primary efficacy endpoint was measured by Investigator’s Global Assessment (IGA) score of 0/1 at 16 weeks and all adverse events (AEs) experienced by patients were recorded. Results Of the 93 patients included in the study, 51 (55%) reached IGA 0/1 and 38 (41%) experienced ≥1 AE. There were no severe AEs or discontinuation prior to 16 weeks due to an AE. Conclusions These findings suggest a higher IGA-based efficacy profile with no newly identified safety concerns in patients treated with dupilumab at two tertiary hospitals in Toronto, Canada, compared to those in randomized controlled trials.


2016 ◽  
Vol 116 (S 02) ◽  
pp. S13-S23 ◽  
Author(s):  
A. Camm ◽  
Craig Coleman ◽  
CAPT Tamayo ◽  
Jan Beyer-Westendorf

SummaryRandomised controlled trials (RCTs) are considered the gold standard of clinical research as they use rigorous methodologies, detailed protocols, pre-specified statistical analyses and well-defined patient cohorts. However, RCTs do not take into account the complexity of real-world clinical decision-making. To tackle this, real-world data are being increasingly used to evaluate the long-term safety and effectiveness of a given therapy in routine clinical practice and in patients who may not be represented in RCTs, addressing key clinical questions that may remain. Real-world evidence plays a substantial role in supporting the use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in clinical practice. By providing data on patient profiles and the use of anticoagulation therapies in routine clinical practice, real-world evidence expands the current awareness of NOACs, helping to ensure that clinicians are well-informed on their use to implement patient-tailored clinical decisions. There are various issues with current anticoagulation strategies, including under- or overtreatment and frequent monitoring with VKAs. Real-world studies have demonstrated that NOAC use is increasing (Dresden NOAC registry and Global Anticoagulant Registry in the FIELD-AF [GARFIELD-AF]), as well as reaffirming the safety and effectiveness of rivaroxaban previously observed in RCTs (XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation [XANTUS] and IMS Disease Analyzer). This article will describe the latest updates in real-world evidence across a variety of methodologies, such as non-interventional studies (NIS), registries and database analyses studies. It is anticipated that these studies will provide valuable clinical insights into the management of thromboembolism, and enhance the current knowledge on anticoagulant use and outcomes for patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rafael K. Alaiti ◽  
Bruno T. Saragiotto ◽  
Leandro Fukusawa ◽  
Nayra D.A. Rabelo ◽  
Anamaria S. de Oliveira

Abstract Background Clinicians commonly try to use mechanism-based knowledge to make sense of the complexity and uncertainty of chronic pain treatments to create a rationale for their clinical decision-making. Although this seems intuitive, there are some problems with this approach. Discussion The widespread use of mechanism-based knowledge in clinical practice can be a source of confusion for clinicians, especially when complex interventions with different proposed mechanisms of action are equally effective. Although the available mechanistic evidence is still of very poor quality, in choosing from various treatment options for people with chronic pain, an approach that correctly incorporates mechanistic reasoning might aid clinical thinking and practice. Conclusion By explaining that not all evidence of mechanism is the same and by making a proposal to start using mechanism-based knowledge in clinical practice properly, we hope to help clinicians to incorporate mechanistic reasoning to prioritize and start choosing what may best work for whom.


2009 ◽  
Vol 62 (3) ◽  
pp. 332-333
Author(s):  
Manuel F. Jiménez-Navarro ◽  
Fernando Cabrera-Bueno ◽  
Antonio J. Muñoz-García ◽  
Eduardo de Teresa-Galván

2019 ◽  
Vol 23 (1) ◽  
pp. 133-141 ◽  
Author(s):  
Ian Chau ◽  
Dung T. Le ◽  
Patrick A. Ott ◽  
Beata Korytowsky ◽  
Hannah Le ◽  
...  

Abstract Background There are few third-line or later (3L+) treatment options for advanced/metastatic (adv/met) gastric cancer/gastroesophageal junction cancers (GC/GEJC). 3L+ Nivolumab demonstrated encouraging results in Asian patients in the ATTRACTION-2 study compared with placebo (12-month survival, 26% vs 11%), and in Western patients in the single-arm CheckMate 032 study (12-month survival, 44%). This analysis aimed to establish comparator cohorts of US patients receiving routine care in real-world (RW) clinical practice. Methods A 2-step matching process generated RW cohorts from Flatiron Health’s oncology database (January 1, 2011–April 30, 2017), for comparison with each trial: (1) clinical trial eligibility criteria were applied; (2) patients were frequency-matched with trial arms for baseline variables significantly associated with survival. Median overall survival (OS) was calculated by Kaplan–Meier analysis from last treatment until death. Results Of 742 adv/met GC/GEJC patients with at least 2 prior lines of therapy, matching generated 90 US RW ATTRACTION-2-matched patients (median OS: 3.5 months) versus 163 ATTRACTION-2 placebo patients (median OS: 4.1 months), and 100 US RW CheckMate 032-matched patients (median OS: 2.9 months) versus 42 CheckMate 032 nivolumab-treated patients (median OS: 8.5 months). Baseline characteristics were generally similar between clinical trial arms and RW-matched cohorts. Conclusions We successfully developed RW cohorts for comparison with data from clinical trials, with comparable baseline characteristics. Survival in US patients receiving RW care was similar to that seen in Asian patients receiving placebo in ATTRACTION-2; survival with nivolumab in CheckMate 032 appeared favorable compared with US RW clinical practice.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3489-3489
Author(s):  
Lauren Willis ◽  
Pan Chen ◽  
Katie S Lucero

Introduction: Two surveys were conducted to understand the rationale for hematologists/oncologists (hem/oncs) to seek continuing medical education (CME) as well as how the information is applied to clinical practice. Additionally, we studied the clinical decision making of hem/oncs who treat patients with multiple myeloma (MM) in order to understand the areas to focus for future CME activities. Methods: We conducted two incentivized surveys where only hem/oncs in the US who treat patients were eligible: 1) MM decision-making survey (MM survey) in November 2018 where they were asked case-based questions to assess practice patterns and they were asked to rate their level of confidence in their decisions for the cases; and 2) Information seeking behaviors and preferences survey (behavior survey) in May and June 2019 where they responded to questions about what information informs practice and how often they need new information. Physicians were paid for their participation in the surveys. Results: 93 hem/oncs participated in the behavior survey with 56% from the community setting and 44% practicing exclusively in an academic setting. Community hem/oncs visit online CME more frequently than academic hem/oncs (daily or at least once a week: 67 vs 51%, respectively). The primary factors driving hem/oncs to access online CME include the need to learn about the latest developments (45%) and looking for an answer to a specific question (25%). Community hem/oncs are 2x more likely than academic hem/oncs to access online CME in order to earn credits. All of the hem/oncs surveyed have modified or implemented a new clinical practice in the last year, with the majority of the modified or new practices related to treatment (69%). Community hem/oncs are 174% more likely than academic hem/oncs to use CME as the source of the information leading to modified/new practice (27% vs 10%). The influence of CME on clinical practices is especially striking among hem/oncs practicing in a community vs academic setting on both gaining more confidence in their current practices (71% vs 59%) and modifying treatment practices (64% vs 54%). There were 101 hem/oncs who participated in the MM survey with 51% practicing in the community setting and 55% seeing between 1 to 10 patients with MM per month, whereas 22% saw more than 20 patients with MM per month. Case 1 highlights the lack of confidence among hem/oncs in making treatment decisions for patients with relapsed/refractory MM, with the majority, between 55% to 72%, only somewhat or not confident in their clinical decision. Although various options would be acceptable and not harmful, ideally treatment decisions would be made with a sense of confidence. In case 2, a striking 48% of hem/oncs would use a bortezomib-based regimen in a patient who has severe peripheral neuropathy, despite bortezomib's known side effect of peripheral neuropathy. For those who would use carfilzomib (52%) or a non-bortezomib regimen (13%), less than half (42% and 46%, respectively) were confident in their decision. Case 3 highlights the complexity of tailoring therapy for patients with MM as any of the answers could be appropriate, but between 37% and 67% of hem/oncs were only somewhat or not confident in their choices, indicating a need for additional education. Conclusions: Large Impact of CME on Community Hem/Oncs: A majority of hem/oncs access online CME at least once a week in order to learn about the latest developments and to find answers to specific questions, with the need for CME credits being a minor driver of CME consumption. The data show that CME has a high impact on clinical practices as the majority of hem/oncs surveyed modified or implemented new clinical practices in the last year as a result of what was learned in CME activities. The impact of CME on clinical practices is particularly striking among hem/oncs who practice in community-based settings. Additional Multiple Myeloma-Focused CME is Needed:The treatment paradigm for MM is rapidly evolving and this analysis shows that in order to improve the skills of hem/oncs as well as their confidence in their clinical decision making, additional CME is needed in the areas of (1) individualizing treatment for R/R MM, (2) managing adverse events, and (3) selecting maintenance therapy for high-risk MM. Table Disclosures No relevant conflicts of interest to declare.


VASA ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 163-176 ◽  
Author(s):  
Weidenhagen ◽  
Bombien ◽  
Meimarakis ◽  
Geisler ◽  
A. Koeppel

Open surgical repair of lesions of the descending thoracic aorta, such as aneurysm, dissection and traumatic rupture, has been the “state-of-the-art” treatment for many decades. However, in specialized cardiovascular centers, thoracic endovascular aortic repair and hybrid aortic procedures have been implemented as novel treatment options. The current clinical results show that these procedures can be performed with low morbidity and mortality rates. However, due to a lack of randomized trials, the level of reliability of these new treatment modalities remains a matter of discussion. Clinical decision-making is generally based on the experience of the vascular center as well as on individual factors, such as life expectancy, comorbidity, aneurysm aetiology, aortic diameter and morphology. This article will review and discuss recent publications of open surgical, hybrid thoracic aortic (in case of aortic arch involvement) and endovascular repair in complex pathologies of the descending thoracic aorta.


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