scholarly journals Efficient Adaptive Randomization and Stopping Rules in Multi-arm Clinical Trials for Testing a New Treatment

2012 ◽  
Vol 31 (4) ◽  
pp. 441-457 ◽  
Author(s):  
Tze Leung Lai ◽  
Olivia Yueh-Wen Liao
Keyword(s):  
Clinical Trials ◽  
Stopping Rules ◽  
Adaptive Randomization ◽  
New Treatment

scholarly journals Treatment for mitochondrial diseases

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tongling Liufu ◽  
Zhaoxia Wang
Keyword(s):  
Clinical Trials ◽  
Nuclear Dna ◽  
Mitochondrial Diseases ◽  
Cochrane Collaboration ◽  
Potential Bias ◽  
Leber Hereditary Optic Neuropathy ◽  
Pharmacological Agents ◽  
Unpublished Studies ◽  
New Treatment ◽  
Allotopic Expression

AbstractMitochondrial diseases are predominantly caused by mutations of mitochondrial or nuclear DNA, resulting in multisystem defects. Current treatments are largely supportive, and the disorders progress relentlessly. Nutritional supplements, pharmacological agents and physical therapies have been used in different clinical trials, but the efficacy of these interventions need to be further evaluated. Several recent reviews discussed some of the interventions but ignored bias in those trials. This review was conducted to discover new studies and grade the original studies for potential bias with revised Cochrane Collaboration guidelines. We focused on seven published studies and three unpublished studies; eight of these studies showed improvement in outcome measurements. In particular, two of the interventions have been tested in studies with strict design, which we believe deserve further clinical trials with a large sample. Additionally, allotopic expression of the ND4 subunit seemed to be an effective new treatment for patients with Leber hereditary optic neuropathy.

Unified exact design with early stopping rules for single arm clinical trials with multiple endpoints

2021 ◽  
pp. 096228022110130
Author(s):  
Wei Wei ◽  
Denise Esserman ◽  
Michael Kane ◽  
Daniel Zelterman
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Decision Rules ◽  
Stopping Rules ◽  
Multiple Endpoints ◽  
Shiny App ◽  
R Shiny ◽  
Early Phase Clinical Trials ◽  
User Friendly ◽  
Exact Design

Adaptive designs are gaining popularity in early phase clinical trials because they enable investigators to change the course of a study in response to accumulating data. We propose a novel design to simultaneously monitor several endpoints. These include efficacy, futility, toxicity and other outcomes in early phase, single-arm studies. We construct a recursive relationship to compute the exact probabilities of stopping for any combination of endpoints without the need for simulation, given pre-specified decision rules. The proposed design is flexible in the number and timing of interim analyses. A R Shiny app with user-friendly web interface has been created to facilitate the implementation of the proposed design.

Dystrophinopathies and Limb-Girdle Muscular Dystrophies

2017 ◽  
Vol 48 (04) ◽  
pp. 262-272 ◽  
Author(s):  
Anna Sarkozy ◽  
Mariacristina Scoto ◽  
Francesco Muntoni ◽  
Joana Domingos
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Shoulder Girdle ◽  
Muscle Disease ◽  
Standards Of Care ◽  
Muscular Dystrophies ◽  
New Treatment ◽  
Shoulder Girdle Muscles ◽  
Independent Ambulation ◽  
Duchenne's Muscular Dystrophy

AbstractMuscular dystrophies are a heterogeneous group of inherited diseases. The natural history of these disorders along with their management have changed mainly due to a better understanding of their pathophysiology, the evolution of standards of care, and new treatment options. Dystrophinopathies include both Duchenne's and Becker's muscular dystrophies, but in reality they are a spectrum of muscle diseases caused by mutations in the gene that encodes the protein dystrophin. Duchenne's muscular dystrophy is the most common form of inherited muscle disease of childhood. The current standards of care considerably prolong independent ambulation and survival. Several therapeutic options either aiming at substituting/correcting the primary protein defect or limiting the progression of the dystrophic process are currently being explored in clinical trials.Limb-girdle muscular dystrophies (LGMDs) are rare and heterogeneous conditions, characterized by weakness and wasting of the pelvic and shoulder girdle muscles. Originally classified into dominant and recessive, > 30 genetic forms of LGMDs are currently recognized. Further understanding of the pathogenic mechanisms of LGMD will help identifying novel therapeutic approaches that can be tested in clinical trials.

A03 Powerspending in clinical trials using alpha-spending stopping rules

1993 ◽  
Vol 14 (5) ◽  
pp. 400
Author(s):  
Jim van Rossum ◽  
Gerrit-Anne van Es
Keyword(s):  
Clinical Trials ◽  
Stopping Rules

scholarly journals ALS Clinical Trials Review: 20 Years of Failure. Are We Any Closer to Registering a New Treatment?

2017 ◽  
Vol 9 ◽  
Author(s):  
Dmitry Petrov ◽  
Colin Mansfield ◽  
Alain Moussy ◽  
Olivier Hermine
Keyword(s):  
Clinical Trials ◽  
New Treatment

scholarly journals Hemophilia gene therapy: ushering in a new treatment paradigm?

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 226-233
Author(s):  
Lindsey A. George
Keyword(s):  
Clinical Trial ◽  
Gene Therapy ◽  
Clinical Trials ◽  
Hemophilia A ◽  
Full Potential ◽  
Proof Of Concept ◽  
Aav Vector ◽  
Treatment Paradigm ◽  
Clinical Trial Enrollment ◽  
New Treatment

Abstract After 3 decades of clinical trials, repeated proof-of-concept success has now been demonstrated in hemophilia A and B gene therapy. Current clinical hemophilia gene therapy efforts are largely focused on the use of systemically administered recombinant adeno-associated viral (rAAV) vectors for F8 or F9 gene addition. With multiple ongoing trials, including licensing studies in hemophilia A and B, many are cautiously optimistic that the first AAV vectors will obtain regulatory approval within approximately 1 year. While supported optimism suggests that the goal of gene therapy to alter the paradigm of hemophilia care may soon be realized, a number of outstanding questions have emerged from clinical trial that are in need of answers to harness the full potential of gene therapy for hemophilia patients. This article reviews the use of AAV vector gene addition approaches for hemophilia A and B, focusing specifically on information to review in the process of obtaining informed consent for hemophilia patients prior to clinical trial enrollment or administering a licensed AAV vector.

scholarly journals Perspectives on Immunotherapy of Metastatic Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yongjiu Dai ◽  
Wenhu Zhao ◽  
Lei Yue ◽  
Xinzheng Dai ◽  
Dawei Rong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Liver Metastasis ◽  
Experimental Design ◽  
Poor Prognosis ◽  
Response Rate ◽  
Traditional Treatment ◽  
The Poor ◽  
New Thinking ◽  
New Treatment

Colorectal cancer, especially liver metastasis, is still a challenge worldwide. Traditional treatment such as surgery, chemotherapy and radiotherapy have been difficult to be further advanced. We need to develop new treatment methods to further improve the poor prognosis of these patients. The emergence of immunotherapy has brought light to mCRC patients, especially those with dMMR. Based on several large trials, some drugs (pembrolizumab, nivolumab) have been approved by US Food and Drug Administration to treat the patients diagnosed with dMMR tumors. However, immunotherapy has reached a bottleneck for other MSS tumors, with low response rate and poor PFS and OS. Therefore, more clinical trials are underway toward mCRC patients, especially those with MSS. This review is intended to summarize the existing clinical trials to illustrate the development of immunotherapy in mCRC patients, and to provide a new thinking for the direction and experimental design of immunotherapy in the future.

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