scholarly journals The interaction between equipoise and logistics in clinical trials: A case study

2017 ◽  
Vol 14 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Meredith G Warshaw ◽  
Vincent J Carey ◽  
Elizabeth J McFarland ◽  
Liza Dawson ◽  
Elaine Abrams ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Specific Treatment ◽  
Standard Of Care ◽  
Design Stage ◽  
Ethical Review ◽  
Clinical Equipoise ◽  
Expert Clinician ◽  
Barriers To Enrollment

Introduction: Equipoise is usually discussed as an ethical issue in clinical trials. However, it also has practical implications. Background: Clinical equipoise is usually construed to mean uncertainty or disagreement among the expert clinician community. However, an individual physician’s sense of equipoise may vary by location, based on the local standard of care or availability of specific treatment options, and these differences can affect providers’ willingness to enroll participants into clinical trials. There are also logistical barriers to enrollment in international trials due to prolonged timelines for approvals by government agencies and ethical review boards. Case Study: A multinational clinical trial of bridging strategies for treatment of non-adherent HIV-infected youth, experienced differing perceptions of equipoise due to disparities in availability of treatment options by country. Unfortunately, the countries with most demand for the trial were those where the approval process was most delayed, and the study was closed early due to slow accrual. Discussion: When planning multicenter clinical trials, it is important to take into account heterogeneity among research sites and try to anticipate differences in equipoise and logistical factors between sites, in order to plan to address these issues at the design stage.

scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

scholarly journals New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy

2021 ◽  
Author(s):  
Suresh Victor ◽  
Eridan Rocha-Ferreira ◽  
Ahad Rahim ◽  
Henrik Hagberg ◽  
David Edwards
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Therapeutic Hypothermia ◽  
Treatment Options ◽  
Standard Of Care ◽  
High Income ◽  
Hypoxic Ischemic Encephalopathy ◽  
Pharmacodynamic Modelling ◽  
Dose Ranging ◽  
Ischemic Encephalopathy

AbstractAround 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade. Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments. What is Known:• Therapeutic hypothermia is beneficial in neonatal hypoxic-ischemic encephalopathy.• Neonates with moderate or severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia still experience severe sequelae. What is New:• Erythropoietin, allopurinol, melatonin, cannabidiol, and exendin-4/exenatide show promise in conjunction with therapeutic hypothermia.• There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials.

Is There a Precise Adjuvant Therapy for Esophagogastric Carcinoma?

2018 ◽  
pp. 280-291 ◽  
Author(s):  
Elizabeth Cartwright ◽  
Florence K. Keane ◽  
Peter C. Enzinger ◽  
Theodore Hong ◽  
Ian Chau
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Global Consensus ◽  
Esophagogastric Cancer ◽  
Genetic Features ◽  
Related Mortality ◽  
Optimal Treatment Strategy

Esophagogastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis for patients with locally advanced disease is poor and the majority of patients with operable tumors treated with surgery alone will have recurrent disease. A multimodal approach to treatment with adjunctive chemotherapy or chemoradiotherapy is therefore the standard of care for these patients. However, there is no global consensus on the optimal treatment strategy and international guidelines vary. National clinical trials inform local practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy combinations are all possible treatment options in the management of resectable esophagogastric cancer. A number of clinical trials are ongoing, which seek to directly compare multimodal treatment options and hope to provide clarity in this area. Furthermore, increased understanding of the molecular and genetic features of esophagogastric cancer may help to guide management of operable disease by determining optimal patient selection through identification of predictive biomarkers of response and the application of novel targeted agents.

CASTRATION-RESISTANT PROSTATE CANCER: NEW PERSPECTIVES IN PHARMACOLOGICAL TREATMENT

2019 ◽  
Vol 25 (1) ◽  
pp. 49-58
Author(s):  
Dmitry A. Andreev ◽  
A. A Zavyalov ◽  
A. V Govorov ◽  
K. A. Kokushkin ◽  
M. Y Davidovskaya
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Treatment Options ◽  
Specific Treatment ◽  
Cochrane Library ◽  
Cancer Drug ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Treatment Algorithms ◽  
Castration Resistant

Prostate cancer remains one of the most actual problems in oncourology due to its high prevalence and resistance to therapy. Within 5 years of active treatment and follow-up, the castration-resistant prostate cancer (CRPC) develops in 10-20% of patients. This type of disease course resists treatments and leads to death. Medical resources distinguish two different forms of CRPC: non-metastatic and metastatic. Such separation is critically important because each of two forms requires different treatment algorithms. This paper summarizes the main outlines of foreign clinical guidelines and reviews the new treatment options for non-metastatic and metastatic CRPC as wells as the design and results of key clinical trials on drug efficiency. To prepare the review, the comprehensive literature search was conducted using PubMed/Medline, the Cochrane Library, EMBASE, CyberLeninka, e-library databases. The search line included phrases containing the following words: prostate cancer, castration-resistant prostate cancer, drug therapy, treatment algorithms, clinical studies, etc. In accordance to foreign guidelines, it is essential to determine the high risk patients with non-metastatic CRPC and promptly apply new therapeutic options including apalutamide and enzalutamide, which have proven being effective in clinical trials as therapies that attenuate the transition of the non-metastatic CRPC to the metastatic stage. Foreign medical guidelines propose to apply a wider set of treatment algorithms for patients with metastatic CRPC, for instance: considerations on possibilities to use the cabazitaxel instead of docetaxel in the 1st line therapy in patients with pre-existing mild peripheral neuropathy, etc. as well as new therapies - pembrolizumab and sipuleucel-T. The issues regarding the selection of patients with CRPC for specific treatment algorithms and defining the optimal sequence of therapeutic regimens as well as combining various regimens with minimizing toxic effects and maximizing patient benefits remain unsolved.

scholarly journals Update on the Treatment of Metastatic Urothelial Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Nedal Bukhari ◽  
Humaid O. Al-Shamsi ◽  
Faisal Azam
Keyword(s):  
Clinical Trials ◽  
Urothelial Carcinoma ◽  
Treatment Options ◽  
Standard Of Care ◽  
Line Treatment ◽  
First Line ◽  
Metastatic Urothelial Carcinoma ◽  
Unfit Patients ◽  
Review Reports ◽  
First Line Treatment

Platinum-based combination chemotherapy has been the standard of care in the first-line treatment of metastatic urothelial carcinoma (mUC). Treatment of metastatic disease following progression on platinum-based regimens has evolved significantly in the last few years. Clinical trials are currently ongoing to determine how best to use and sequence these treatments. In this minireview, we will review current first-line treatment options in both cisplatin fit and cisplatin unfit patients and advances in first- and second-line treatments including chemotherapy and immunotherapy. This review reports key findings from the clinical trials especially highlighting the importance of PD-1 and PD-L1 inhibitors in the treatment of bladder/urothelial carcinomas.

The Potential for Therapeutic Misconception in Pulmonary Arterial Hypertension Clinical Trials: A Case-Based Discussion

2010 ◽  
Vol 9 (4) ◽  
pp. 220-222
Author(s):  
David B. Badesch ◽  
Marilyn E. Coors ◽  
Deborah H. McCollister ◽  
Todd Bull ◽  
Alison Lakin
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Conflicts Of Interest ◽  
Medical Knowledge ◽  
Study Drug ◽  
Clinical Equipoise ◽  
Therapeutic Misconception ◽  
Pulmonary Arterial

This case study illustrates several of the potential challenges frequently encountered by clinical investigators working in the area of pulmonary arterial hypertension (PAH). It raises the issues of therapeutic misconception and clinical equipoise, and illustrates the importance of informing potential research participants of all their options in explicit detail.20 It also emphasizes the importance of explaining to patients that they are being asked to participate in a study to advance medical knowledge and develop therapies for the population of patients with PAH, and not for their own benefit. While they may benefit from the study drug, if they in fact receive it, this should not be offered as a reason for their potential participation. In addition, investigators should disclose any potential conflicts of interest to potential participants. During the past 2 decades, such clinical trials have advanced the treatment of patients with PAH and continue to offer the possibility of further improvements in our treatment of this devastating disease.

scholarly journals Immune checkpoint inhibitors in genitourinary malignancies

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
M. Thana ◽  
L. Wood
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Urothelial Carcinoma ◽  
Metastatic Disease ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Current Evidence ◽  
Testicular Germ Cell ◽  
Testicular Germ Cell Tumours

Although immune-mediated therapies have been used in genitourinary (gu) malignancies for decades, recent advances with monoclonal antibody checkpoint inhibitors (cpis) have led to a number of promising treatment options. In renal cell carcinoma (rcc), cpis have been shown to have benefit over conventional therapies in a number of settings, and they are the standard of care for many patients with metastatic disease. Based on recent data, combinations of cpis and antiangiogenic therapies are likely to become a new standard approach in rcc. In urothelial carcinoma, cpis have been shown to have a role in the second-line treatment of metastatic disease, and a number of clinical trials are actively investigating cpis for other indications. In other gu malignancies, such as prostate cancer, results to date have been less promising. Immunotherapies continue to be an area of active study for all gu disease sites, with several clinical trials ongoing. In this review, we summarize the current evidence for cpi use in rcc, urothelial carcinoma, prostate cancer, testicular germ-cell tumours, and penile carcinoma. Ongoing clinical trials of interest are highlighted, as are the challenges that clinicians and patients will potentially face as immune cpis become a prominent feature in the treatment of gu cancers.

Usefulness and applicability of next generation sequencing in neuroendocrine neoplasms.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 626-626
Author(s):  
Sorrapong Manyanont ◽  
Kyle Winter ◽  
Nikolaos Trikalinos
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Genetic Counseling ◽  
Treatment Options ◽  
Standard Of Care ◽  
The Body ◽  
Neuroendocrine Neoplasms ◽  
Mutational Status ◽  
Investigational Treatment ◽  
Metastatic Setting

626 Background: Neuroendocrine neoplasms (NENs) are rare tumors that can arise anywhere in the body and treatment options are limited due to their rarity. Knowledge of their mutational status might allow for tumor agnostic treatments or aid in enrollment in clinical trials, especially in the metastatic setting. Methods: Eligible NEN patients on an institutional, IRB approved protocol, who had NGS as standard of care and were treated in the past 24 months were included. Tumors were categorized by location and histologic grade. We explored the actual and theoretical eligibility for tumor agnostic treatments and enrollment in clinical trials as available on clinicaltrials.gov. Results: Between August 2017 and July 2019 a total of 107 patients were eligible. Globally 102 clinical trials included patients with NEN and specific mutations.NGS detected one (1%) case of MSI high and one (1) TRK fusion positive tumor, eligible for checkpoint inhibitor and TRK inhibitor therapy respectively. Moreover, NGS identified 16 (15%) cases of MEN1, 1 (1%) of RET, 2 (2%) of NF1 and 3 (2.8%) of MUTYH, 2 (2%) TSC or TSC2, BRCA in 1(1%). These patients were appropriately referred to genetic counseling. About 51.5% of patients would in theory be eligible for an investigational treatment based on mutations and clinical trial availability. Fifty two of 107 patients (48.5%) would not have been eligible for a clinical trial with reasons varying between no mutations (24%), sample failure (8.4%) or nonactionable mutations (15.9%). Conclusions: NGS can point to clinical trial eligibility and guide genetic counseling and should probably be a standard approach in the evaluation of new metastatic NEN patients.

scholarly journals Fibroelastolytic Papulosis in a Middle-Age Female: Presentation and Review of Treatment

2019 ◽  
Vol 3 (3) ◽  
pp. 215-218
Author(s):  
Carl Barrick ◽  
An Guo Michael Chin ◽  
Veronica Rutt ◽  
Nektarios Lountzis ◽  
Cynthia Bartus
Keyword(s):  
Treatment Guidelines ◽  
Treatment Options ◽  
Specific Treatment ◽  
Standard Of Care ◽  
Additional Treatment ◽  
Left Shoulder ◽  
Management Options ◽  
Clinical Presentations ◽  
Topical Retinoids ◽  
Previously Treated

Introduction:Fibroelastolytic papulosis (FEP) is a rare, benign, acquired cutaneous disease with a histopathology that shows variable fibrosis and elastolysis of the papillary dermis. FEP clinically presents as white-ivory to yellow papules and plaques commonly occurring on the neck. Prior to this date there have been no specific treatment guidelines for FEP, thus various management options are explored in this case report. Case Report:We present a 62-year-old female with an isolated ivory, cobblestoned plaque with open comedones on the left shoulder since childhood. The histopathology confirmed the diagnosis of FEP. The patient had been previously treated with topical clindamycin, salicylic acid, tretinoin, and tazarotene without success.Conclusion: This case demonstrates the importance of recognizing FEP, as clinical presentations can vary. FEP can be distressing to patients, and it is important to explore additional treatment options. Treatment options including topical retinoids and ablative lasers have been reported, but with limited and inconsistent success. However, due to the rarity of the disease there is currently no standard of care for the treatment of FEP and additional successful treatment options are needed.

Using real-world cohorts to assess the generalizability and relevance of randomized clinical trials (RCTs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6540-6540 ◽  
Author(s):  
Caroline Savage Bennette ◽  
Nathan Coleman Nussbaum ◽  
Melissa D. Curtis ◽  
Neal J. Meropol
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Real World Data ◽  
Eligibility Criteria ◽  
Relevance Score ◽  
World Data

6540 Background: RCTs are the gold standard for understanding the efficacy of new treatments, however, patients (pts) in RCTs often differ from those treated in the real-world. Further, selecting a standard of care (SOC) arm is challenging as treatment options may evolve during the course of a RCT. Our objective was to assess the generalizability and relevance of RCTs supporting recent FDA approvals of anticancer therapies. Methods: RCTs were identified that supported FDA approvals of anticancer therapies (1/1/2016 - 4/30/2018). Relevant pts were selected from the Flatiron Health longitudinal, EHR-derived database, where available. Two metrics were calculated: 1) a trial’s pt generalizability score (% of real-world pts receiving treatment consistent with the control arm therapy for the relevant indication who actually met the trial's eligibility criteria) and 2) a trial’s SOC relevance score (% of real-world pts with the relevant indication and meeting the trial's eligibility criteria who actually received treatment consistent with the control arm therapy). All analyses excluded real-world pts treated after the relevant trial’s enrollment ended. Results: 14 RCTs across 5 cancer types (metastatic breast, advanced non-small cell lung cancer, metastatic renal cell carcinoma, multiple myeloma, and advanced urothelial) were included. There was wide variation in the SOC relevance and pt generalizability scores. The median pt generalizability score was 63% (range 35% - 88%), indicating that most real-world pts would have met the RCT eligibility criteria. The median SOC relevance score was 37% (range 15% - 74%), indicating that most RCT control arms did not reflect the way trial-eligible real-world pts in the US were actually treated. Conclusions: There is great variability across recent RCTs in terms of pt generalizability and relevance of SOC arms. Real-world data can be used to inform selection of control arms, predict impact of inclusion/exclusion criteria, and also assess the generalizability of the results of completed trials. Incorporating real-world data in planning and interpretation of prospective clinical trials could improve accrual and enhance relevance of RCT outcomes.

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