trial Alyssa Milano on why she went to Trump’s impeachment trial, and how Schiff’s presentation was like ‘watching a one-man show’ By www.washingtonpost.com Published On :: Fri, 24 Jan 2020 00:17:15 +0000 The actress and activist wants to encourage the public to get involved because “showing up is participating in how this all works.” Full Article
trial CBD Notification SCBD/IMS/JMF/NS/88541 (2020-002): Preparations for the trial phase of an Open-ended Forum for review of implementation to be held during the third meeting of the Subsidiary Body on Implementation, 27 May 2020 - Montreal, Canada By www.cbd.int Published On :: Mon, 06 Jan 2020 00:00:00 GMT Full Article
trial NIH clinical trial tests remdesivir plus anti-inflammatory drug baricitinib for COVID-19 By www.eurekalert.org Published On :: Fri, 08 May 2020 00:00:00 EDT (NIH/National Institute of Allergy and Infectious Diseases) A randomized, controlled clinical trial evaluating the safety and efficacy of a treatment regimen of the investigational antiviral remdesivir plus the anti-inflammatory drug baricitinib for COVID-19 has begun. The trial is now enrolling hospitalized adults with COVID-19 in the United States. The trial is expected to open at approximately 100 US and international sites. Investigators currently anticipate enrolling more than 1,000 participants. The National Institute of Allergy and Infectious Diseases is sponsoring the trial. Full Article
trial Addressing the ethical considerations of SARS-CoV-2 human challenge trials By www.eurekalert.org Published On :: Thu, 07 May 2020 00:00:00 EDT (American Association for the Advancement of Science) While an effective vaccine for the SARS-CoV-2 virus is likely many months away, development could be accelerated by conducting controlled human infection (CHI) studies -- which are increasingly being considered by the scientific community due to the urgent need. Full Article
trial Quantitative proteomics of human heart samples collected in vivo reveal the remodeled protein landscape of dilated left atrium without atrial fibrillation By feedproxy.google.com Published On :: 2020-04-14 Nora LinscheidApr 14, 2020; 0:RA119.001878v1-mcp.RA119.001878Research Full Article
trial 3-year freedom from progression following 68GaPSMA PET CT triaged management in men with biochemical recurrence post radical prostatectomy. Results of a prospective multi-center trial. By jnm.snmjournals.org Published On :: 2019-11-01T13:36:36-07:00 Background: 68Ga PSMA PET CT (PSMA) is increasingly used in men with biochemical recurrence (BCR) post radical prostatectomy (RP), but its longer term prognostic / predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for 3 year freedom from progression (FFP) in men with BCR post RP undergoing salvage radiotherapy (sRT). Methods: This prospective multi-center study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA with rising PSA following RP. Management following PSMA was recorded but not mandated. PSMA protocols were standardised across sites and reported prospectively. Clinical, pathological and surgical information, sRT, timing and duration of androgen deprivation (ADT), 3 year PSA results and clinical events were documented. FFP was defined as a PSA rise ≤ 0.2ng/mL above nadir post sRT, with no additional treatment. Results: The median PSA was 0.26ng/mL (IQR 0.15 - 0.59) and follow-up 38 months (IQR 31-43). PSMA was negative in 34.6% (90/260), confined to prostate fossa 21.5% (56/260), pelvic nodes 26.2% (68/260), and distant disease 17.7% (46/260). 71.5% (186/260) received sRT, 38.2% (71/186) to the fossa only, 49.4% (92/186) fossa + pelvic nodes and 12.4% (23/186) nodes alone/SBRT. PSMA was highly predictive of FFP at 3 years following sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative/fossa confined vs. 45% (39/86) for extra fossa disease (p<0.0001). On logistic regression PSMA was more independently predictive of FFP than established clinical predictors, including PSA, T-stage, surgical margin status or Gleason score (P < 0.002). 32% of men with a negative PSMA PET did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59ng/mL over the 3 years. Conclusion: PSMA PET result is highly predictive of FFP at 3 years in men undergoing sRT for BCR following RP. In particular, men with negative PSMA PET or disease identified as still confined to the prostate fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional ADT than those with extra fossa disease. Full Article
trial Long term follow-up and outcomes of re-treatment in an expanded 50 patient single-center phase II prospective trial of Lutetium-177 (177Lu) PSMA-617 theranostics in metastatic castrate-resistant prostate cancer By jnm.snmjournals.org Published On :: 2019-11-22T10:43:33-08:00 Objectives: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castrate-resistant prostate cancer (mCRPC). We now report their longer-term outcomes including a 20 patient extension cohort and outcomes of subsequent systemic treatments following completion of trial therapy. Methods: 50 patients with PSMA-avid mCRPC who had progressed after standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Endpoints included PSA response (PCWG2), toxicity (CTCAE v4.03), imaging response, patient-reported health-related quality of life (QoL), progression-free and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including LuPSMA. Results: 75 men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 months) and extensive prior treatment including prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). The mean administered radioactivity was 7.5 GBq/cycle. PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with ≥ 80% decrease. Of 27 patients with measurable soft tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to LuPSMA were self-limiting G1-2 dry mouth (66%), transient G1-2 nausea (48%), G3-4 thrombocytopenia (10%) and G3 anemia (10%). Brief pain inventory severity and interference scores decreased at all time points including at the 3 month follow-up with a decrease of -1.2 (95% CI -0.5 to -1.9, P = 0.001) and 1.0 (95% CI -0.2 to -0.18, P = 0.013), respectively. At a median follow-up of 31.4 months, median OS was 13.3 months (95% CI 10.5-18.7) with a significantly longer survival of 18.4 months (95% CI 13.8-23.8) in patients achieving a PSA decline ≥ 50%. At progression following prior response, further LuPSMA was administered to 15 (30%) patients (median 2 cycles commencing 359 days from enrolment) with PSA decline ≥ 50% in 11 patients (73%). 4 of 21 patients (19%) receiving other systemic therapies upon progression experienced PSA decline ≥ 50%. There were no unexpected adverse events with LuPSMA re-treatment. Conclusion: This expanded 50 patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity and improved QoL with LuPSMA radioligand therapy. Upon progression, re-challenge LuPSMA demonstrated higher response rates than other systemic therapies. Full Article
trial Positron lymphography via intracervical 18F-FDG injection for pre-surgical lymphatic mapping in cervical and endometrial malignancies By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Rationale: The presence of metastasis in local lymph nodes (LNs) is a key factor influencing choice of therapy and prognosis in cervical and endometrial cancers; therefore, the exploration of sentinel LNs (SLNs) is highly important. Currently, however, SLN mapping requires LN biopsy for pathologic evaluation, since there are no clinical imaging approaches that can identify tumor-positive LNs in early stages. Staging lymphadenectomy poses risks, such as leg lymphedema or lymphocyst formation. Furthermore, in 80% to 90% of patients, the explored LNs are ultimately tumor free, meaning the vast majority of patients are unnecessarily subjected to lymphadenectomy. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG except one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG, except for one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Conclusion: This first-in-human study of PLG in women with uterine and cervical cancer demonstrates its feasibility and its ability to identify patients with nodal metastases, and warrants further evaluation in additional studies. Full Article
trial 64Cu-DOTATATE PET/CT for Imaging Patients with Known or Suspected Somatostatin Receptor-Positive Neuroendocrine Tumors: Results of the First US Prospective, Reader-Blinded Clinical Trial By jnm.snmjournals.org Published On :: 2020-01-31T13:36:41-08:00 Studies demonstrate that the investigational 64Cu-DOTATATE radiopharmaceutical may provide diagnostic and logistical benefits over available imaging agents for patients with somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs). Accordingly, we aimed to prospectively determine the lowest dose of 64Cu-DOTATATE that facilitates diagnostic quality scans and evaluated the diagnostic performance and safety in a phase III study of patients with SSTR-expressing NETs. Methods: A dose-ranging study was conducted in 12 patients divided into 3 dose groups (111 MBq [3.0 mCi], 148 MBq [4.0 mCi], and 185 MBq [5.0 mCi] ± 10%) to determine the lowest dose of 64Cu-DOTATATE that produced diagnostic quality PET/CT images. Using the 64Cu-DOTATATE dose identified in the dose-ranging study, 3 independent nuclear medicine physicians who were blinded to all clinical information read PET/CT scans from 21 healthy volunteers and 42 NET-positive patients to determine those with "Disease" and "No Disease," as well as "Localized" versus "Metastatic" status. Blinded-reader evaluations were compared to a patient-specific standard of truth (SOT), which was established by an independent oncologist who used all previously available pathology, clinical, and conventional imaging data. Diagnostic performance calculated for 64Cu-DOTATATE included sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. Inter- and intra-reader reliability, as well as ability to differentiate between localized and metastatic disease, was also determined. Adverse events (AEs) were recorded from 64Cu-DOTATATE injection through 48 hours post-injection. Results: The dose-ranging study identified 148 MBq (4.0 mCi) as the optimal dose to obtain diagnostic quality PET/CT images. Following database lock, diagnostic performance from an initial majority read of the 3 independent readers showed a significant 90.9% sensitivity (P = 0.0042) and 96.6% specificity (P < 0.0001) for detecting NETs, which translated to a 100.0% sensitivity and 96.8% specificity after correcting for an initial SOT misread. Excellent inter- and intra-reader reliability, as well as ability to distinguish between localized and metastatic disease, was also noted. No AEs were related to 64Cu-DOTATATE, and no serious AEs were observed. Conclusion: 64Cu-DOTATATE PET/CT is a safe imaging technique that provides high-quality and accurate images at a dose of 148 MBq (4.0 mCi) for the detection of somatostatin-expressing NETs. Full Article
trial First-in-Human Trial of Dasatinib-Derivative Tracer for Tumor Kinase-Targeted Positron Emission Tomography By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 We developed a first-of-kind dasatinib-derivative imaging agent, 18F-SKI-249380 (18F-SKI), and validated its use for noninvasive in vivo tyrosine kinase-targeted tumor detection in preclinical models. In this study, we assess the feasibility of using 18F-SKI for PET imaging in patients with malignancies. Methods: Five patients with a prior diagnosis of breast cancer, renal cell cancer, or leukemia underwent whole-body PET/CT imaging 90 min post-injection of 18F-SKI (mean: 241.24 ± 116.36 MBq) as part of a prospective study. In addition, patients underwent either a 30-min dynamic scan of the upper abdomen including, at least partly, cardiac left ventricle, liver, spleen, and kidney (n = 2) or three 10-min whole-body PET/CT scans (n = 3) immediately post-injection and blood-based radioactivity measurements to determine the time course of tracer distribution and facilitate radiation dose estimates. A subset of three patients had a delayed whole-body PET/CT scan at 180 min. Biodistribution, dosimetry, and tumor uptake were quantified. Absorbed doses were calculated using OLINDA/EXM 1.0. Results: No adverse events occurred after injection of 18F-SKI. A total of 27 tumor lesions were analyzed with median SUVpeak 1.4 (range, 0.7–2.3) and tumor-to-blood ratios of 1.6 (range, 0.8–2.5) at 90 min post-injection. Intratumoral drug concentrations calculated for four reference lesions ranged from 0.03–0.07 nM. In all reference lesions, constant tracer accumulation was observed between 30–90 min post-injection. Blood radio-assay indicated that radiotracer clearance from blood and plasma was initially rapid (blood half-time 1.31 ± 0.81 min, plasma 1.07 ± 0.66 min; n = 4), followed variably by either a prolonged terminal phase (blood half-time 285 ± 148.49 min, plasma 240 ± 84.85 min; n = 2) or a small rise to plateau (n = 2). Like dasatinib, 18F-SKI underwent extensive metabolism post-administration, as evidenced by metabolite analysis. Radioactivity was predominantly cleared via the hepatobiliary route. The highest absorbed dose estimates (mGy/MBq) in normal tissues were to the right colon (0.167 ± 0.04) and small intestine (0.153 ± 0.03). The effective dose was 0.0258 (SD 0.0034) mSv/MBq. Conclusion: 18F-SKI demonstrated significant tumor uptake, distinct image contrast despite low injected doses, and rapid clearance from blood. Full Article
trial Moving towards multicenter therapeutic trials in ALS: feasibility of data pooling using different TSPO positron emission tomography (PET) radioligands. By jnm.snmjournals.org Published On :: 2020-04-03T15:14:37-07:00 Rationale: Neuroinflammation has been implicated in Amyotrophic Lateral Sclerosis (ALS) and can be visualized using translocator protein (TSPO) radioligands. To become a reliable pharmacodynamic biomarker for ALS multicenter trials, some challenges have to be overcome. We aimed to investigate whether multicenter data pooling of different TSPO tracers (11C-PBR28 and 18F-DPA714) is feasible, after validation of an established 11C-PBR28 PET pseudoreference analysis technique for 18F-DPA714. Methods: 7 ALS-Belgium (58.9±6.7 years,5M) and 8 HV-Belgium (52.1±15.2 years,3M); and 7 ALS-US (53.4±9.8 years,5M) and 7 HV-US (54.6±9.6 years,4M) from a previously published study (1) underwent dynamic 18F-DPA714 (Leuven, Belgium) or 11C-PBR28 (Boston, US) PET-MR scans. For 18F-DPA714, volume of distribution (VT) maps were compared to standardized uptake value ratios (SUVR)40-60 calculated using the pseudoreference regions (1)cerebellum, (2)occipital cortex, and (3)whole brain without ventricles (WB-ventricles). Also for 11C-PBR28, SUVR60-90 using WB-ventricles were calculated. Results: In line with previous studies, increased 18F-DPA714 uptake (17.0±5.6%) in primary motor cortices was observed in ALS, as measured by both VT and SUVR40-60 approaches. Highest sensitivity was found for SUVRWB-ventricles (average cluster 21.6±0.1%). 18F-DPA714 VT ratio and SUVR40-60 results were highly correlated (r>0.8, p<0.001). A similar pattern of increased uptake (average cluster 20.5±0.5%) in primary motor cortices was observed in ALS with 11C-PBR28 using the SUVRWB-ventricles. Analysis of the 18F-DPA714 and 11C-PBR28 data together, resulted in a more extensive pattern of significant increased glial activation in the bilateral primary motor cortices. Conclusion: The same pseudoreference region analysis technique for 11C-PBR28 PET imaging can be extended towards 18F-DPA714 PET. Therefore, in ALS, standardized analysis across these two tracers enables pooling of TSPO PET data across multiple centers and increase power of TSPO as biomarker for future therapeutic trials. Full Article
trial Impact of 68Ga-PSMA-11 PET on the Management of recurrent Prostate Cancer in a Prospective Single-Arm Clinical Trial By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 Introduction: Prostate-specific membrane antigen ligand positron emission tomography (PSMA PET) induces management changes in patients with prostate cancer. We aim to better characterize the impact of PSMA PET on management of recurrent prostate cancer in a large prospective cohort. Methods: We report management changes following PSMA PET, a secondary endpoint of a prospective multicenter trial in men with prostate cancer biochemical recurrence. Pre-PET (Q1), Post-PET (Q2) and Post-Treatment (Q3) questionnaires were sent to referring physicians recording site of recurrence, intended (Q1 to Q2 change) and implemented (Q3) therapeutic and diagnostic management. Results: Q1/Q2 response was collected for 382/635 (60%, intended cohort), Q1/Q2/Q3 for 206 patients (32%, implemented cohort). Intended management change (Q1/2) occurred in 260/382 (68%) patients. Intended change (Q1/2) was considered major in 176/382 (46%) patients. Major changes occurred most often for patients with PSA of 0.5 to <2.0 ng/mL (81/147, 55%). By analysis of stage-groups, management change was consistent with PET disease location, i.e. majority of major changes towards active surveillance (47%) for unknown disease site (103/382, 27%), towards local/focal therapy (56%) for locoregional disease (126/382, 33%), and towards systemic therapy (69% M1a; 43% M1b/c) for metastatic disease (153/382, 40%). According to Q3 responses, intended management was implemented in 160/206 (78%) patients. A total of 150 intended diagnostic tests, mostly CT (n = 43, 29%) and bone Scans/NaF-PET (n = 52, 35%), were prevented by PSMA PET; 73 tests, mostly biopsies (n = 44, 60%) as requested by the study protocol, were triggered (Q1/2). Conclusion: According to referring physicians, sites of recurrence were clarified by PSMA PET and disease localization translated into management changes in more than half of patients with biochemical recurrence of prostate cancer. Full Article
trial Quantitative proteomics of human heart samples collected in vivo reveal the remodeled protein landscape of dilated left atrium without atrial fibrillation [Research] By feedproxy.google.com Published On :: 2020-04-14T13:35:16-07:00 Genetic and genomic research has greatly advanced our understanding of heart disease. Yet, comprehensive, in-depth, quantitative maps of protein expression in hearts of living humans are still lacking. Using samples obtained during valve replacement surgery in patients with mitral valve prolapse (MVP), we set out to define inter-chamber differences, the intersect of proteomic data with genetic or genomic datasets, and the impact of left atrial dilation on the proteome of patients with no history of atrial fibrillation (AF). We collected biopsies from right atria (RA), left atria (LA) and left ventricle (LV) of seven male patients with mitral valve regurgitation with dilated LA but no history of AF. Biopsy samples were analyzed by high-resolution mass spectrometry (MS), where peptides were pre-fractionated by reverse phase high-pressure liquid chromatography prior to MS measurement on a Q-Exactive-HF Orbitrap instrument. We identified 7,314 proteins based on 130,728 peptides. Results were confirmed in an independent set of biopsies collected from three additional individuals. Comparative analysis against data from post-mortem samples showed enhanced quantitative power and confidence level in samples collected from living hearts. Our analysis, combined with data from genome wide association studies suggested candidate gene associations to MVP, identified higher abundance in ventricle for proteins associated with cardiomyopathies and revealed the dilated LA proteome, demonstrating differential representation of molecules previously associated with AF, in non-AF hearts. This is the largest dataset of cardiac protein expression from human samples collected in vivo. It provides a comprehensive resource that allows insight into molecular fingerprints of MVP and facilitates novel inferences between genomic data and disease mechanisms. We propose that over-representation of proteins in ventricle is consequent not to redundancy but to functional need, and conclude that changes in abundance of proteins known to associate with AF are not sufficient for arrhythmogenesis. Full Article
trial Risk Factors for Diabetic Peripheral Neuropathy and Cardiovascular Autonomic Neuropathy in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study By diabetes.diabetesjournals.org Published On :: 2020-05-01 Barbara H. BraffettMay 1, 2020; 69:1000-1010Complications Full Article
trial Widening the drug trial net has the potential to reduce respiratory failure By feeds.bmj.com Published On :: Friday, May 8, 2020 - 09:29 Full Article
trial Online CBT is trialled for children with chronic fatigue syndrome By feeds.bmj.com Published On :: Tuesday, November 1, 2016 - 06:30 Full Article
trial Trial of novel leukaemia drug is stopped for second time after two more deaths By feeds.bmj.com Published On :: Friday, November 25, 2016 - 10:46 Full Article
trial NICE recommends implantable monitor to identify atrial fibrillation after stroke By feeds.bmj.com Published On :: Tuesday, January 14, 2020 - 00:30 Full Article
trial The BMJ requires data sharing on request for all trials By feeds.bmj.com Published On :: Fri, 22 May 2015 13:22:11 +0000 The movement to make data from clinical trials widely accessible has achieved enormous success, and it is now time for medical journals to play their part. From 1 July The BMJ will extend its requirements for data sharing to apply to all submitted clinical trials, not just those that test drugs or devices. The BMJ's Elizabeth Loder explains what... Full Article
trial The evidence manifesto - better trials, better use of trial data By feeds.bmj.com Published On :: Fri, 21 Apr 2017 15:48:21 +0000 We're creating a manifesto for better evidence. The centre for Evidence Based Medicine at the University of Oxford, and the BMJ, are asking what are the problem with medical evidence, and how can we fix them? In this second discussion we went to Nottingham University, to find out what the people who create the bread and butter of EBM -... Full Article
trial MVA85A trial investigation - press conference. By feeds.bmj.com Published On :: Thu, 11 Jan 2018 18:34:38 +0000 Trial MVA85A - monkey trials for a booster vaccine for BCG, developed by researchers at Oxford University, is the subject of an investigation published on bmj.com. Experts warn that today’s investigation is just one example of “a systematic failure” afflicting preclinical research and call for urgent action “to make animal research more fit for... Full Article
trial Vinay Prasad - there is overdiagnosis in clinical trials By feeds.bmj.com Published On :: Wed, 03 Oct 2018 17:11:07 +0000 We want clinical trials to be thorough - but Vinay Prasad, assistant professor of medicine at Oregon Health Science University, argues that the problem of overdiagnosis may be as prevalent, in the way we measure disease in our research, as our practice. In this podcast he joins us to discuss the problem, and why he thinks what qualifies as... Full Article
trial Acceptable, tolerable, manageable - but not to patients. How drug trials report harms. By feeds.bmj.com Published On :: Mon, 19 Nov 2018 18:02:11 +0000 You’ll have read in a clinical trial “Most patients had an acceptable adverse-event profile.” Or that a drug “has a manageable and mostly reversible safety profile.” And that “the tolerability was good overall.” In this podcast, Bishal Gyawali (@oncology_bg) joins us to describe what events those terms were actually describing in cancer drug... Full Article
trial Cancer drug trials used for regulatory approval are at risk of bias By feeds.bmj.com Published On :: Thu, 19 Sep 2019 14:09:14 +0000 Around half of trials that supported new cancer drug approvals in Europe between 2014 and 2016 were judged to be at high risk of bias, in a new study. Huseyin Naci,assistant professor of health policy a the London School of Economics joins us to talk about why potential bias may mean potential exaggeration of treatment effects, and could be... Full Article
trial How Blockchain could improve clinical trial transparency By feeds.bmj.com Published On :: Sat, 12 Oct 2019 13:06:50 +0000 Blockchain is the digital technology that underpins cryptocurrencies such as bitcoin, and has been proposed as the digital panacea of our times. But Leeza Osipenko, from the London School of Economics, has thought about how it could actually be used in clinical trials, and what else would need to change in our regulatory environment to make that... Full Article
trial Hypoglycemia in the Diabetes Control and Complications Trial By diabetes.diabetesjournals.org Published On :: 1997-02-01 The Diabetes Control and Complications Trial Research GroupFeb 1, 1997; 46:271-286Original Article Full Article
trial The Relationship of Glycemic Exposure (HbA1c) to the Risk of Development and Progression of Retinopathy in the Diabetes Control and Complications Trial By diabetes.diabetesjournals.org Published On :: 1995-08-01 The Diabetes Control and Complications Trial Research GroupAug 1, 1995; 44:968-983Original Article Full Article
trial On Trial: Agricultural Biotechnology in Africa By feedproxy.google.com Published On :: Wed, 16 Jul 2014 10:58:30 +0000 21 July 2014 Download PDF Rob Bailey Former Research Director, Energy, Environment and Resources @ClimateRob Robin WilloughbyDavid Grzywacz Increasing agricultural productivity and adapting farming to climate change are central to Africa’s development prospects. There are important opportunities to enhance yields and increase resilience through the adoption of improved crop varieties. In some cases, biotechnology, and in particular genetic modification (GM), offers advantages over conventional plant-breeding approaches. Accordingly there are a various projects under way to develop new GM varieties for African farmers, ranging from drought-resistant maize to varieties of cassava, banana, sorghum, cowpea and sweet potato with resistance to pests and disease.In addition to government funds, these projects have also attracted the support of influential donor agencies and philanthropic foundations. However, despite the expenditure of considerable resources, the potential of GM in Africa is not being realized. So far no GM trait developed for African farmers has been put to use.Multiple barriers inhibit the development and adoption of pro-poor GM varieties in Africa. On the demand side, farmers may be reluctant to adopt GM varieties owing to a lack of export opportunities and distrust of the technology among local consumers. Farmers may also be concerned about exploitation by transnational seed companies (despite the fact that development of new GM technologies in Africa is dominated by the public sector). On the supply side, donor funding struggles to match the long timescales of research and development, while incentives among research scientists may be poorly aligned with farmer outcomes. Non-existent, poorly functioning or overly punitive regulatory regimes discourage investment.The most important barriers – such as regulatory constraints, consumer distrust and weak farmer demand – must be understood in the context of wider social and political dynamics surrounding GM, typified by misinformation, polarized public discourse, and dysfunctional and opportunistic politics. The result is most GM projects becoming ‘stuck’ at the field trial stage without ever progressing to release. This ‘convenient deadlock’ of continual field trials allows governments to manage political risks by effectively balancing the demands of pro-GM and anti-GM lobbies – proponents of GM have a pipeline of technologies, while opponents are appeased by the failure of any to gain approval. The disabling socio-political environment for GM development in Africa greatly reduces the efficacy of investment in this technology.This has two important implications. First, technology development needs to be located within a wider project of transformation that engages key actors – most notably politicians, policy-makers and farmers – as stakeholders from the outset, and includes strategies to address multiple demand- and supply-side barriers. Second, successful adoption is more likely in countries with less disabling political conditions, characterized by lower levels of consumer distrust and opposition, genuine farmer demand and demonstrable commitment from government. Focusing efforts and resources on a small number of ‘best bet’ countries will also allow donors and technology providers to support more ambitious, transformational projects led by national governments. Department/project Energy, Environment and Resources Programme Full Article
trial Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial By feeds.bmj.com Published On :: Wednesday, March 25, 2020 - 22:31 Full Article
trial Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials By feeds.bmj.com Published On :: Wednesday, April 1, 2020 - 22:31 Full Article
trial Prospective registration and reporting of trial number in randomised clinical trials: global cross sectional study of the adoption of ICMJE and Declaration of Helsinki recommendations By feeds.bmj.com Published On :: Tuesday, April 14, 2020 - 09:20 Full Article
trial Sex Difference in Effects of Low-Dose Aspirin on Prevention of Dementia in Patients With Type 2 Diabetes: A Long-term Follow-up Study of a Randomized Clinical Trial By care.diabetesjournals.org Published On :: 2020-01-20T12:00:30-08:00 OBJECTIVE To evaluate and compare the efficacy of long-term use of low-dose aspirin for the prevention of dementia in men and women. RESEARCH DESIGN AND METHODS This study is a follow-up cohort study of the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial, which was a randomized, open-label, standard care–controlled trial examining the effects of low-dose aspirin on cardiovascular events. We followed up 2,536 Japanese patients with type 2 diabetes (T2D) enrolled in the JPAD trial from 2002 to 2017. The primary outcome of this post hoc analysis was the incidence of dementia, which was defined by the prescription of antidementia drugs or admission due to dementia. RESULTS Among the originally enrolled patients, 2,121 (84%) retained their original allocation. During a median follow-up of 11.4 years, 128 patients developed dementia. The overall effect of low-dose aspirin on the prevention of dementia adjusted for age, sex, and other established risk factors was not significant (hazard ratio [HR] 0.82, 95% CI 0.58–1.16). However, a significant reduction was seen in the risk of dementia in women (HR 0.58, 95% CI 0.36–0.95), but not in men (HR 1.27, 95% CI 0.75–2.13) (Pinteraction = 0.03). CONCLUSIONS Long-term use of low-dose aspirin may reduce the risk for dementia in women with T2D. Full Article
trial Targeting CXCR1/2 Does Not Improve Insulin Secretion After Pancreatic Islet Transplantation: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Type 1 Diabetes By care.diabetesjournals.org Published On :: 2020-03-20T11:50:34-07:00 OBJECTIVE Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients. RESEARCH DESIGN AND METHODS A phase 3, multicenter, randomized, double-blind, parallel-assignment study (NCT01817959) was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 ± 5 after the first and day 365 ± 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control. RESULTS The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression. CONCLUSIONS In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage. Full Article
trial Within-Trial Evaluation of Medical Resources, Costs, and Quality of Life Among Patients With Type 2 Diabetes Participating in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) By care.diabetesjournals.org Published On :: 2020-01-20T12:00:30-08:00 OBJECTIVE To compare medical resource use, costs, and health utilities for 14,752 patients with type 2 diabetes who were randomized to once-weekly exenatide (EQW) or placebo in addition to usual diabetes care in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). RESEARCH DESIGN AND METHODS Medical resource use data and responses to the EuroQol 5-Dimension (EQ-5D) instrument were collected at baseline and throughout the trial. Medical resources and medications were assigned values by using U.S. Medicare payments and wholesale acquisition costs, respectively. Secondary analyses used English costs. RESULTS Patients were followed for an average of 3.3 years, during which time those randomized to EQW experienced 0.41 fewer inpatient days (7.05 vs. 7.46 days; relative rate ratio 0.91; P = 0.05). Rates of outpatient medical visits were similar, as were total inpatient and outpatient costs. Mean costs for nonstudy diabetes medications over the study period were ~$1,600 lower with EQW than with placebo (P = 0.01). Total within-study costs, excluding study medication, were lower in the EQW arm than in the placebo arm ($28,907 vs. $30,914; P ≤ 0.01). When including the estimated cost of EQW, total mean costs were significantly higher in the EQW group than in the placebo group ($42,697 vs. $30,914; P < 0.01). With English costs applied, mean total costs, including exenatide costs, were £1,670 higher in the EQW group than the placebo group (£10,874 vs. £9,204; P < 0.01). There were no significant differences in EQ-5D health utilities between arms over time. CONCLUSIONS Medical costs were lower in the EQW arm than the placebo arm, but total costs were significantly higher once the cost of branded exenatide was incorporated. Full Article
trial Lipid and Inflammatory Cardiovascular Risk Worsens Over 3 Years in Youth With Type 2 Diabetes: The TODAY clinical trial By care.diabetesjournals.org Published On :: 2013-06-01 TODAY Study GroupJun 1, 2013; 36:1758-1764TODAY Study Full Article
trial Kidney Disease and Related Findings in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study By care.diabetesjournals.org Published On :: 2014-01-01 Ian H. de BoerJan 1, 2014; 37:24-30DCCT/EDIC 30th Anniversary Summary Findings Full Article
trial New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Oral Agents and Basal Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 2) By care.diabetesjournals.org Published On :: 2014-12-01 Hannele Yki-JärvinenDec 1, 2014; 37:3235-3243Emerging Technologies and Therapeutics Full Article
trial Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia By care.diabetesjournals.org Published On :: 2016-07-01 Bernhard J. HeringJul 1, 2016; 39:1230-1240Emerging Technologies and Therapeutics Full Article
trial Overnight Closed-Loop Insulin Delivery in Young People With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial By care.diabetesjournals.org Published On :: 2014-05-01 Roman HovorkaMay 1, 2014; 37:1204-1211Advances in Artificial Pancreas Development Full Article
trial Empagliflozin as Add-On to Metformin in Patients With Type 2 Diabetes: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial By care.diabetesjournals.org Published On :: 2014-06-01 Hans-Ulrich HäringJun 1, 2014; 37:1650-1659Emerging Technologies and Therapeutics Full Article
trial Update on Cardiovascular Outcomes at 30 Years of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study By care.diabetesjournals.org Published On :: 2014-01-01 John M. LachinJan 1, 2014; 37:39-43DCCT/EDIC 30th Anniversary Summary Findings Full Article
trial A Low-Glycemic Load Diet Facilitates Greater Weight Loss in Overweight Adults With High Insulin Secretion but Not in Overweight Adults With Low Insulin Secretion in the CALERIE Trial By care.diabetesjournals.org Published On :: 2005-12-01 Anastassios G. PittasDec 1, 2005; 28:2939-2941BR Clinical Care/Education/Nutrition Full Article
trial New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Basal and Mealtime Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 1) By care.diabetesjournals.org Published On :: 2014-10-01 Matthew C. RiddleOct 1, 2014; 37:2755-2762Emerging Technologies and Therapeutics Full Article
trial Rapid Rise in Hypertension and Nephropathy in Youth With Type 2 Diabetes: The TODAY clinical trial By care.diabetesjournals.org Published On :: 2013-06-01 TODAY Study GroupJun 1, 2013; 36:1735-1741TODAY Study Full Article
trial Neuropathy and Related Findings in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study By care.diabetesjournals.org Published On :: 2014-01-01 Catherine L. MartinJan 1, 2014; 37:31-38DCCT/EDIC 30th Anniversary Summary Findings Full Article
trial Sodium-Glucose Cotransporter 2 Inhibition and Glycemic Control in Type 1 Diabetes: Results of an 8-Week Open-Label Proof-of-Concept Trial By care.diabetesjournals.org Published On :: 2014-05-01 Bruce A. PerkinsMay 1, 2014; 37:1480-1483Novel Communications in Diabetes Full Article
trial Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The Finnish Gestational Diabetes Prevention Study (RADIEL): A Randomized Controlled Trial By care.diabetesjournals.org Published On :: 2016-01-01 Saila B. KoivusaloJan 1, 2016; 39:24-30Considerations in the Management of Gestational Diabetes Mellitus Full Article
trial Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a Diabetes Care Editors Expert Forum By care.diabetesjournals.org Published On :: 2018-01-01 William T. CefaluJan 1, 2018; 41:14-31Diabetes Care Expert Forum Full Article
trial The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 Years: Overview By care.diabetesjournals.org Published On :: 2014-01-01 David M. NathanJan 1, 2014; 37:9-16DCCT/EDIC 30th Anniversary Summary Findings Full Article
trial CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis By care.diabetesjournals.org Published On :: 2016-07-01 Ele FerranniniJul 1, 2016; 39:1108-1114Diabetes Care Symposium Full Article