Sunday, 26 April 2015

Research Day DrArie Blows the lid on Statitistics

As we have seen there are lies damn lies and statistics. Very few understand statistics properly and with a bit of statistical magic you can make a bland study look interesting. Today Dr.Arie explains some of the intricacies of the clinical trial



Medical cannabis not yet the the Apirin of the 21St Centuary

Belendiuk KA, Baldini LL, Bonn-Miller MO. Narrative review of the safety and efficacy of marijuana for the treatment of commonly state-approved medical and psychiatric disorders.
Addict Sci Clin Pract. 2015 21;10(1):10. [Epub ahead of print]


The present investigation aimed to provide an objective narrative review of the existing literature pertaining to the benefits and harms of marijuana use for the treatment of the most common medical and psychological conditions for which it has been allowed at the state level. Common medical conditions for which marijuana is allowed (i.e., those conditions shared by at least 80 percent of medical marijuana states) were identified as: Alzheimer's disease, amyotrophic lateral sclerosis, cachexia/wasting syndrome, cancer, Crohn's disease, epilepsy and seizures, glaucoma, hepatitis C virus, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis and muscle spasticity, severe and chronic pain, and severe nausea. Post-traumatic stress disorder was also included in the review, as it is the sole psychological disorder for which medical marijuana has been allowed. Studies for this narrative review were included based on a literature search in PsycINFO, MEDLINE, and Google Scholar. Findings indicate that, for the majority of these conditions, there is insufficient evidence to support the recommendation of medical marijuana at this time. A significant amount of rigorous research is needed to definitively ascertain the potential implications of marijuana for these conditions. It is important for such work to not only examine the effects of smoked marijuana preparations, but also to compare its safety, tolerability, and efficacy in relation to existing pharmacological treatments.
There is simply not the definitive evidence that cannabis does this or that, yet there are many pot docs and pot heads claiming it does everything. This is then used as part of the legalise recreational cannabis campaign. It is very strange that medical cannabis has been approved in so many States in the USA, whilst the FDA are making companies including GW pharma jump through hoops to demonstrate that their drugs do something. I am sure that compounds in cannabis can have medical benefit and work on biology that is useful in the control of MS symptoms and progression. To address the later it is most likely to be trials with medical marijuana to show this but how do you control a trial with cannabis, because if you don't know you are getting it, you are not getting enough to be useful....It's the biology

Baker D, Pryce G, Jackson SJ, Bolton C, Giovannoni G.The biology that underpins the therapeutic potential of cannabis-based medicines for the control of spasticity in multiple sclerosis.
Mult Scler Relat Disord. 2012;1(2):64-75.

Cannabis-based medicines have recently been approved for the treatment of pain and spasticity in multiple sclerosis (MS). This supports the original perceptions of people with MS, who were using illegal street cannabis for symptom control and pre-clinical testing in animal models of MS. This activity is supported both by the biology of the disease and the biology of the cannabis plant and the endocannabinoid system. MS results from disease that impairs neurotransmission and this is controlled by cannabinoid receptors and endogenous cannabinoid ligands. This can limit spasticity and may also influence the processes that drive the accumulation of progressive disability.

AAN 2015: conference highlight

Good news for Alzheimer's Disease underscores the principle of treating early in neurodegeneration. #AAN2015 #MSBlog #MSResearch

"Many people have asked me what was my highlight of the AAN 2015 meeting. To be honest it was not MS-related data, but early data from a phase 1b/2a study of a new monoclonal antibody, aducanumab, that targets the so called A-beta protein in early Alzheimer's Disease (AD). The study was a safety and dose finding study of an antibody that targets a specific protein aggregate that is found in AD and is hypothesised to cause the disease. The study showed a dose response (see figure below) and, despite its small size, had an effect on cognition. Other studies using this approach have failed. Why? This study was in ADers with very early or asymptomatic disease; targeting the pathology before you have frank dementia may be the secret to why this study was positive. Another reason may be that aducanumab is simply better at neutralising toxic species of the A-beta protein, the so called oligomers, than the other similar antibodies studied to date."

"Why is this study important to MSers? It reinforces the therapeutic principle in neurodegenerative diseases, MS included, that if want to target the neurodegenerative diseases you need to do so in the so called presymptomatic phase. In other words we should be targeting progressive MS before it becomes clinically apparent. The other reason it is important to MSers is that if we do our jobs properly and look after you brain you may be susceptible to the development of AD in the future. It is estimated  that 1 in 3 of us who live long enough will get AD. Therefore you may need to be treated for AD in  the future. I have scoured the literature and I am not sure if anyone has described AD pathology in MS. I suspect it is because nobody has done a systematic look."

"It is early days and it is clear that this data will now form the basis of a large clinical development programme in AD."

Click here to download poster

Sevigny et al. RANDOMIZED, DOUBLE‐BLIND, PLACEBO‐CONTROLLED, PHASE IB STUDY OF ADUCANUMAB (BIIB037), AN ANTI‐AB MONOCLONAL ANTIBODY, IN PATIENTS WITH PRODROMAL OR MILD ALZHEIMER’S DISEASE: INTERIM RESULTS BY DISEASE STAGE AND APOE4 STATUS. AAN 2015

Objective: Aducanumab (BIIB037) is a human monoclonal antibody selective for aggregated forms of beta‐amyloid peptide being investigated as a disease‐modifying treatment for AD.

Background: This Phase 1b study is evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of aducanumab in patients with prodromal or mild AD.

Design/Methods: Patients included in this multicenter, randomized, double‐blind, placebo‐controlled, multiple‐dose study (PRIME; NCT01677572) were aged 50‐90 years, had a positive florbetapir (18F‐AV‐45) PET scan, and met clinical criteria for prodromal or mild AD. During the double‐blind, placebo‐controlled phase, patients received aducanumab or placebo once every 4 weeks for 52 weeks. In a staggered, ascending‐dose design, patients were randomized to 1 of 7 treatment arms stratified by ApoE4 status (carrier/non‐carrier). We present results from an interim analysis (after subjects in all arms completed at least the Week 26 visit) on safety and change in florbetapir PET signal by disease stage and ApoE4 status.

Results: Patients (N=166) were randomized to placebo (n=40), 1 (n=31), 3 (n=33), 6 (n=30) or 10 (n=32) mg/kg aducanumab. Of 165 patients dosed, 65% were ApoE4 carriers (35% non‐carriers) and 41% had prodromal AD (59% mild). The incidence (based on MRI) of the most common AE (amyloid‐related imaging abnormalities [ARIA]) was dose‐ and ApoE4‐status?dependent (for ARIA‐edema or ‐microhemorrhage or ‐hemosiderosis: ApoE4 carriers, 11%, 14%, 43% and 65% for 1, 3, 6 and 10 mg/kg aducanumab, respectively, versus 8% for placebo; ApoE4 non‐carriers, 8%, 18%, 11%, and 17% versus 0%). Treatment‐related dose‐ and time‐dependent reductions in brain beta‐amyloid plaque (shown by SUVR reduction) at Weeks 26 and 54 were consistent across mild and prodromal subgroups and across ApoE4 carriers and non‐carriers within the doses tested.

Conclusions: ARIA was the main safety and tolerability finding and was dose‐and ApoE4‐dependent. Aducanumab reduced beta‐amyloid plaque across mild and prodromal stages, and ApoE4 carriers and non‐carriers. 

 Study Supported By: Biogen Idec Inc and Neurimmune Holding AG