Kohkan Shamsi, MD, PhD Co-Authors "Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial"
November 17, 2016
Summary
Background
Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease.
Read More
 
Kohkan Shamsi, MD, PhD, presents "Imaging in Alzheimer's Disease Trials: Impact on Patient Recruitment, Retention and Logistics" at the 2016 Alzheimer's Association International Conference in Toronto, ON
September 13, 2016
 
JAMA Article on Gadolinium Exposure and Parkinson’s: A False Sense of Safety? ~Welk B, McArthur E, Marrow SA, et al. Association between Gadolinium contrast Exposure and the Risk of Parkinsonism. JAMA 2016;316:96-98
August 09, 2016
Dr. Welk and colleagues conducted a retrospective review of multiple linked administrative databases from Ontario, Canada to evaluate association between Gadolinium contrast agent exposure and the risk of Parkinsonism in patients who underwent contrast enhanced MRI (1). In this large population based study, the authors have concluded that the result does not support the hypothesis that gadolinium deposits in the Globus pallidus lead to neuronal damage manifesting as Parkinsonism. This conclusion might be overreaching and it may give a false sense of safety to the reader for all gadolinium contrast agents as inference appears to be based on large number of patient data (>99000 patients who received at least 1 dose of gadolinium contrast agent). There are already many commentaries and discussions articles on the web and in the medical community that cast doubt on clinical relevance of gadolinium deposits citing this paper without considering important limitations of the study (2). These limitations also mentioned by the authors, could significantly affect the study results and may not allow to reach the abovementioned conclusion.
One major limitation is number of injections that patients received in this study. Of the total patients included in the study 81.5% received single dose of contrast agent and only 2.5% of the patients underwent 4 or more contrast enhanced MRIs. Almost all published reports have shown that signal intensity increase in Globus Pallidus and Dentate Nucleus is observed only after multiple contrast enhanced MRI (>6 or more contrast enhanced MRIs) (3,4). Furthermore, the authors did not define type of gadolinium agents or the cumulative dose of the contrast agent administered in the studied population. This is extremely important as several studies have shown that gadolinium deposition is dependent the total cumulative dose of gadolinium as well as on chemical structure of contrast agent and thermodynamic and kinetic stability of the gadolinium molecule. Macrocyclic agents are more stable than linear agents (5,6). Signal intensity increase in the brain nuclei due to gadolinium deposits is not observed with macrocyclic agents (Dotarem, Prohance, Gadovist) as they are more stable as compared to the linear agents (Omniscan, Magnevist, Optimark, Multihance) (7,8). As 81.5% of the patients included in this study only received a single dose of gadolinium contrast agent, it is quite possible that patients receiving single dose may have received exclusively macrocyclic agents or small number of patients who received multiple doses, could have received both macrocyclic and linear agents. Based on published literature, even if all of them have received linear agents, the total administered dose is not sufficient to draw any definitive conclusion that gadolinium contrast agents are not related to Parkinsonism
References:
1. Welk B, McArthur E, Marrow SA, et al. Association between Gadolinium contrast Exposure and the Risk of Parkinsonism. JAMA 2016;316:96-98
2. https://www.lawsonresearch.ca/news/study-casts-doubt-clinical-significance-gadolinium-brain-deposits
3. Kanda T, Ishii K, Kawaguchi H, et al. High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-weighted MR Images: Relationship with Increasing Cumulative Dose of a Gadolinium-Based Contrast Material Radiology. 2014;270:834-841
4. Errante Y., Cirimele V, Mallio CA, et al. Progressive Increase of T1 Signal Intensity of the Dentate Nucleus on Unenhanced Magnetic Resonance Images is Associated with Cumulative Doses of Intravenously Administered Gadodiamide in Patients with Normal Renal Function, Suggesting Dechelation Invest Radiol. 2014;49:685-690.
5. Perazella MA. Current status of gadolinium toxicity in patients with kidney disease. Clin J Am Soc Nephrol. 2009;4:461-9
6. Frenzel T, Lengsfeld P, Schirmer H, et al. Stability of Gadolinium-Based Magnetic Resonance Imaging Contrast Agents in Human Serum at 37°C. Invest Radiol 2008;43:817-828
7. Kanda T, Osawa, M, Hiroshi O, et al. High Signal Intensity in Dentate Nucleus on Unenhanced T1-weighted MR Images: Association with Linear versus Macrocyclic Gadolinium Chelate Administration. Radiology 2015: 275: 803-809
8. Radbruch A, Weberling LD, Kieslich PJ, et al. Gadolinium Retention in the Dentate Nucleus and Globus Pallidus is Dependent on the Class of Contrast Agent. Radiology 2015;275:783-791.
 
"Deposition of Gadolinium in After Multiple GBCA Injections: Clinical Trial Prospective" by Kohkan Shamsi, MD, PhD
June 03, 2016
Gadolinium-based contrast agents (GBCAs) are indispensable adjuncts to MRI, with numerous studies showing their efficacy in improving the accuracy of MRI studies. Gadolinium deposition in the brains of patients who received multiple doses of GBCAs has recently been reported. Although it is not yet known if there is a clinical implication of brain deposition of gadolinium, concerns for patient safety are of paramount importance.
Free gadolinium is very toxic and suppression of the reticuloendothelial system, inhibition of phagocytosis, and interruption of the function of smooth and skeletal muscles, haave been documented in animal studies. Therefore, gadolinium in GBCAs, is bound to a chelating agent that should remain bound in vivo.
Based on the chelating agent, GBCAs can be classified as linear and macrocyclic. Macrocyclic GBCAs are more stable than linear agents in terms of in-vivo dissociation of gadolinium from gadolinium-chelate complex.
The highest degree of dissociation has been observed in nonionic linear chelates (e.g. Omniscan) followed by ionic linear (e.g. Magnevist). All 3 macrocyclic GBCAs (Dotarem, Gadovist and Prohance) remained stable in human serum (1).

Deposition of gadolinium in humans has been reported in the bones, liver, lung, kidney, heart, eye, and skin of NSF patients but recently, increased signal intensity in the globus pallidus and dentate nucleus associated with multiple GBCA injections (as few as three injections) has been reported. Autopsy studies have confirmed that this increase in signal intensity observed on MRI is due to gadolinium deposition (2). Almost all the publications showed that the increase in signal intensity is related to linear GBCAs and not associated with macrolyclic GBCAs. (3, 4)

In summary, repeated administration of linear GBCAs can lead to hyperintensity due to gadolinium deposition within the brain. The putative mechanism is the dissociation of the contrast agent into gadolinium and it’s chelate. To date, no consequences for patient health have been identified. However, this is a rapidly evolving topic.
Recognizing this, in 2015, the FDA issued a drug safety communications statement regarding the risk for brain deposits with repeated use of GBCAs for MRI. Although, it concluded that the available information does not identify any adverse health effects, caution should be exercised when using GBCAs. Subsequently, in 2016 the NIH has recommended that macrocyclic GBCA should be used instead of linear GBCAs (6).

Although the long-term impact of deposition of gadolinium in the brain remains unknown, it seems prudent to be careful about the use GBCAs, especially in patients who receive multiple GBCA injections like oncology, neurology and pediatric patients. This new safety concern should also be considered when designing imaging protocols of clinical trials. The protocols of clinical trials should specify type of GBCA that should be used as IRBs may not allow multiple injections of linear GBCAs.

References
1. Frenzel T et al. Stability of Gadolinium-based Magnetic Resonance Imaging Contrast Agents in Human Serum at 37 degrees C. Investigative Radiology 2008; 43:817-28.
2. McDonald RJ. et al. Intracranial Gadolinium Deposition after Contrast-Enhanced MR Imaging.. Radiology. 2015;275(3):772-782.
3. Kanda T, et al. High Signal Intensity in Dentate Nucleus on Unenhanced T1-weighted MR Images: Association with Linear versus Macrocyclic Gadolinium Chelate Administration. Radiology. 2014; 27:834-841.
4. Radbruch A, et al Gadolinium Retention in the Dentate Nucleus and Globus Pallidus is Dependent on the Class of Contrast Agent. Radiology. 2015;275(3):783-791
5. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm456012.htm
6. Malayeri A et al. National Institutes of Health Perspective on Reports of Gadolinium Deposition in the Brain. JACR; 2016; 13: 237-241.
 
Dr. Rick Patt Co-Chairs Main Session at CBI's Imaging in Clinical Trials Conference in Philadelphia, PA on March 28th-29th, 2016
March 29, 2016
Dr. Rick Patt will discuss how to improve reliability and reduce potential risks when implementing imaging endpoints in oncology trials. Read More
 
Kohkan Shamsi, MD, PhD, Co-Founder of BRITI, in collaboration with ICPME, develops an accredited course intended to educate on the potential implications of ordering and performing contrast-enhanced MRIs, especially in those patients who may require multiple scans.
November 04, 2015
Course Overview
The use of gadolinium-based contrast agents in MR imaging has been well-established for 25 years and is an extremely valuable tool for visualizing areas of interest.

However, recent publications have shown hyperintensities on MRI in the dentate nucleus and globus pallidus of patients who have received multiple gadolinium-based contrast injections and have no severe renal insufficiency. Gadolinium deposits have histopathologically been confirmed in the brain tissue of patients exhibiting these hyperintensities. While further research is needed to evaluate the clinical significance of these findings, radiologists, radiologic technologists, and referring physicians must be aware of the potential implications for ordering and performing contrast-enhanced MRI, especially in those patients who may require multiple scans.

Educational Objectives
At the conclusion of this activity, participants should be better able to:
•Explain the classification of GBCAs and clinical relevance of their molecular structures and other physicochemical properties and how these affect patient safety
•Discuss recent studies reporting hyperintensity in the dentate nucleus and globus pallidus on MRI and histopathologically confirmed gadolinium deposits in patients who have undergone multiple contrast-enhanced MRI scans
•Discuss the association of GBCA classification with hyperintensities and gadolinium deposits found in the brain
•Implement the current FDA, ACR, and EMA guidelines for GBCA usage
Read More
 
Kohkan Shamsi, M.D., Ph.D., Presents at CTAD 2015 in Barcelona, Spain - Abstract Title: Increased Utilization of Imaging in Alzheimer Disease (AD) Trials: Impact on Patient Recruitment, Retention and Logistics
June 29, 2015
 
Kohkan Shamsi, M.D., Ph.D., Presents at XXII World Congress of Neurology (WCN 2015) in Santiago, Chile - Abstract Title: Imaging in Alzheimer Disease (AD) Trials
June 29, 2015
 
RSNA 2014 Abstract: Evaluation of a New Manganese-based Orally-Administered Hepatobiliary MR Contrast Agent
March 10, 2015
 
RadMD Presents at ECR 2015: Comparison of a New Manganese-Based Orally-Administered Hepatobiliary MR Contrast Agent with Gd-Chelate-enhanced MR Images for the Evaluation of Focal Liver Lesions
March 09, 2015
 
Rick Patt, M.D. as Session Moderator at the 2014 Translational Imaging Symposium in Boston, MA
October 14, 2014
 
RadMD Presents at Society of Computed Body Tomography and Magnetic Resonance Annual Meeting in New Orleans, LA & RSNA Annual Meeting in Chicago, IL
September 24, 2014
CMC Contrast is developing a new oral Manganese based Liver MRI contrast agent and Dr. Shamsi is supporting the development of this agent. Two papers co-authored by Dr. Rendon Nelson, Department of Radiology, Duke University, and Dr. Shamsi featuring an independent read evaluating efficacy of this contrast agent will be presented at the following meetings: Society of Computed Body Tomography and Magnetic Resonance Annual Meeting in New Orleans, LA on September 30, 2014 during the 1:00-5:00pm session and RSNA Annual Meeting in Chicago, IL on December 2, 2014 at 3:10-3:20pm (Room 353A)
 
RadMD Presents with Theorem Clinical Research at the 7th Clinical Trials Conference on Alzheimer's Disease in Philadelphia, PA on November 22, 2014
September 24, 2014
Dr. Veronica Powell from Theorem Clinical Research and Dr. Kohkan Shamsi will present clinical and statistical considerations for developing training programs for Alzheimer diagnostic and therapeutic trials at CTAD 2014 in Philadelphia, PA on November 22, 2014. Training is a regulatory requirement and for some programs, e.g. amyloid imaging agents, FDA mandated the development and testing of training program as part of the approval process. Dr. Shamsi has been involved in multiple Alzheimer diagnostic and therapeutic clinical trials. Through Blinded Reader and Investigator Training Institute (BRITI), we have trained and tested more than 1,500 trial personnel in >350 sites (PIs, co-Pis, site coordinators etc) and CRO and sponsor personnel in 2013-2014. Read More
 
RadMD Presents at the 3rd Annual Patient Recruitment and Retention America Summit in San Francisco, CA on October 22, 2014 at 12:20-1:00pm
September 24, 2014
Drs. Rick Patt and Kohkan Shamsi will present "Utilizing Imaging Strategies to Improve Patient Recruitment & Retention" at the 3rd Annual Patient Recruitment and Retention America Summit in San Francisco, CA on October 22, 2014 at 12:20-1:00pm.

Presentation Highlights:
• Enhance applicable patient recruitment by confirming patient eligibility through imaging
• Rapid independent confirmation of disease progression reduces inappropriate patient dropout and informative censoring
• Patient management and imaging logistical considerations and their direct impact on patient retention– a case presentation
Read More
 
Dr. Shamsi is presenting ”Role of imaging in Alzheimer disease clinical trials” in 29th International Conference of Alzheimer’s Disease, Puerto Rico, 1-4 May 2014
April 23, 2014
 
RadMD Presents at the 6th Clinical Trials on Alzheimer's Disease Conference in San Diego
November 14, 2013
Thursday, November 14th, 2013. Founder and Co-Principle, Kohkan Shamsi, MD presented at the 6th Annual Conference for Clinical Trials on Alzheimer's Disease in San Diego, CA. His presentation titled: "Increasing Role of Imaging in Alzheimer Disease Trials: Issues and Risk Management Strategies" was presented to a large audience of researchers and industry personnel interested in the evolving field of medical imaging in Alzheimer's Disease clinical trials.

"Increasing Role of Imaging in Alzheimer Disease Trials: Issues and Risk Management Strategies"
Kohkan Shamsi, Founder and Principal, RadMD

Background:
Neuroimaging with magnetic resonance imaging (MRI) and positron emission tomography (PET) is now extensively utilized in Alzheimer disease (AD) clinical trials for patient eligibility, efficacy assessment efficacy, and safety evaluations. MRI is used for structural imaging and PET is used for functional and molecular imaging. The learning objectives of this symposium are:

• To understand role of current MRI and PET techniques utilized in clinical trials, including value of standardization across imaging centers, quality control of data, and qualitative and quantitative analysis strategies

• To outline newer techniques like diffusion tensor weighted MR imaging and amyloid imaging and their role in evaluation of therapeutic agents.

• To understand Amyloid Related Imaging abnormalities (ARIA) and FDA requirements for ARIA monitoring, assessment and patient management

• This symposium will include case studies and discuss issues related to use of imaging technologies. Comprehensive cost effective risk management strategies when using PET and MRI in AD clinical trials will also be presented.

Methods:
MRI and PET are commonly used in AD trials. In multi center trials, standardization of MRI methodology across the sites is essential to acquire consistent data across the sites. This requires prospective site qualification, evaluation of phantom data, training and continuous monitoring. Phantom imaging and standardization is especially important for estimation of brain volumes and comparison of pre and post therapy volumes.

The goals of MRI evaluation in AD trials are:

• To exclude a potentially reversible cause of dementia in subjects with possible Alzheimer’s disease

• To identify subjects at risk for Alzheimer’s disease

• To quantify stage of disease to enable tracking of treatment response

• To evaluate therapeutic response

• To assess presence or absence of Amyloid Related Imaging Abnormalities (ARIA)

In AD trials structural MR imaging is mainly used and in a few trials advance MR imaging techniques such as fMRI and DTI are also incorporated in MRI protocols. To get maximum benefit of MRI and to reduce variability, prospective site qualification, evaluation of phantom data, training and continuous monitoring are necessary. Phantom imaging and standardization is especially important for estimation of brain volumes and comparison of pre and post therapy volumes.

Similarly, PET imaging in AD trials with FDG PET and Amyloid PET has been utilized to evaluate both eligibility evaluations and therapeutic Recent Phase 2-3 anti-amyloid clinical therapeutic trials have extensively used amyloid PET imaging to assess both subject eligibility for enrollment and longitudinal changes in brain amyloid. This has occurred in the absence of full scientific understanding of the longitudinal course of amyloid accumulation as measured by PET over 1 to 2 years assessment periods of a typical therapeutic trial. Considering within-subject longitudinal quantitative assessment of brain amyloid burden with amyloid PET, variance in the imaging outcome is the result of both the subjects' biology and technical issues associated with the specific image analysis approach. Choice of volume of interest (VOI) definition, cortical regions used for the composite SUVr, reference region, spatial normalization approach, and other factors all influence the signal to noise properties of the outcome measure. Different strategies for determination of composite SUVrs may result in trade-offs between variance and signal size which may be optimized for the statistical requirements of the particular study.

As with the MRI site qualification including phantom imaging, image standardization and image acquisition is crucial for the success of efficacy evaluations and high quality poolable quantitative data.

Results and discussion:
Evaluation of Patient Eligibility: Many neurological diseases that could either have similar presentation as AD or could be confounding factors in the assessment of drug therapy have to be excluded to evaluate therapeutic effect of a drug on AD patient population. These include vascular dementia, multiple sclerosis, vascular pathology, neoplasms etc. Inclusion of wrong patients has serious ethical and legal issues. More importantly, these patients could be excluded from the final analysis thereby reducing the sample size and impacting the power of the study and the study results. Patient eligibility can be evaluated either at the site or at a central facility. In this symposium pros and cons of various strategies of eligibility evaluation and optimization of eligibility read process will be discussed including qualitative visual assessments vs. quantitative determination of the eligibility.

Evaluation of Amyloid Related Imaging Abnormalities (ARIA): Initially these abnormalities were observed in monoclonal antibody against amyloid-β (Aβ) trials. These MRI findings include vasogenic edema (ARIA E), micro and macro hemorrhages (ARIA H) and superficial siderosis. FDA has mandated that patients must frequently be followed by MRI in all AD trials and if ARIA is observed, the patient should be discontinued and should be followed by MRI more frequently till the finding is resolved or stabilized. This requirement has put additional burden on both sites and patients who have to undergo MRI every 3 months. These MRIs have to be evaluated in a standardized fashion with very quick turnaround time as patient status in the study is dependent on MRI findings. We will present our experience in conducting MRI evaluations for ARIA and suggest best practices to conduct ARIA evaluations

Efficacy evaluation:
MRI is utilized to evaluate total brain volume and/or hippocampal volume. FDG PET has been used to measure metabolic activity of brain. Recently Amyloid imaging agent has been approved and are being utilized for drug evaluations. In this symposium, we will share our experience regarding issues related to site read, central independent reads, we will also present risk management strategies including protocol development, site selection process, training of the sites and independent reader will be presented.

Conclusion:
In AD trials, utilization of MRI and PET continues to increase for patient eligibility evaluation and to assess efficacy and safety. All aspects of imaging must be prospectively planned including standardizing imaging methodologies across the sites, establishing a uniform site evaluation and site selection process, selecting eligibility and efficacy criteria. Site and independent reader training and testing should be planned and transparently conducted and documented. Knowledge of FDA guidance and relevant appropriateness criteria is essential for designing the imaging protocols and assessment criteria. Risk management strategies, presented in this symposium, should be considered to ensure quality of imaging and optimize results. Quality of imaging is critical not only to ensure that patients are not excluded due to interpretable data but also to get optimum data to evaluate safety and efficacy.

 
RadMD Presents at the 23rd Alzheimer Europe Conference
October 11, 2013
Friday, October 11, 2013 - RadMD Co-founder and Principal, Kohkan Shamsi, MD, PhD presented at the 23rd annual Alzheimer's Europe meeting in Malta. Dr. Shamsi's presentation, "Managing eligibility, amyloid related imaging abnormalities (ARIA), and efficacy evaluations in Alzheimer disease clinical trials: Points to consider" was the only discussion on this critically important topic.
 
RadMD Sponsors The 7th International Meeting on Replicating Oncolytic Virus Therapeutics
June 15, 2013
RadMD announces their Corporate Sponsorship of the 7th International Meeting on Replicating Oncolytic Virus Therapeutics held from June 15-18, 2013 in Quebec City, QC, Canada at the Chateau Frontenac.
 
RadMD to present at the 23rd Alzheimer Europe Conference - St. Julian’s, Malta October 2013
June 07, 2013
RadMD Principal, Kohkan Shamsi, MD, PhD will be presenting at this years Annual Alzheimer's Europe meeting in Malta on October 10 -12, 2013. The topic will be "Managing Eligibility, Amyloid Related Imaging Abnormalities (ARIA), and efficacy evaluations in Alzheimer disease clinical trials: Points to consider"

Alzheimer's disease is extensively being investigated in clinical trials and Imaging is being utilized for patient eligibility, efficacy and safety evaluations. Both Magnetic Resonance Imaging (MRI) and FDG-PET are being used extensively.

The evaluation of images for patient eligibility is critical: Many neurological diseases that could either have a similar presentation as Alzheimer disease or could present confounding factors in the assessment of drug therapy have to be excluded to evaluate therapeutic effect of a drug in an AD patient population. These include vascular dementia, multiple sclerosis, vascular pathology, neoplasms etc. Inclusion of the wrong patient has serious ethical and legal issues. More importantly, these patients could be excluded from the analysis thereby reducing the sample size and impacting the power of the study and the study results.

In this presentation, various strategies of eligibility evaluation will be presented and optimization of the eligibility read process will be discussed.

In the evaluation of Amyloid Related Imaging Abnormalities (ARIA)specialized knowledge is required: Initially these abnormalities were observed in monoclonal antibody anti-amyloid-β (Aβ) trials. These MRI findings include vasogenic edema (ARIA E), micro and macro hemorrhages (ARIA H) and superficial siderosis. The FDA has mandated that patients must frequently be followed by MRI in all AD trials and if ARIA is observed the patient should be discontinued and should be followed by MRI more frequently until the finding is resolved or stabilized. This requirement has put additional burden on both sites and patients who have to undergo MRI every 3 months. These MRIs have to be evaluated in a standardized fashion with a very quick turnaround time as the patient status in the study is dependent on the MRI findings. We will present our experience in conducting MRI evaluations for ARIA and suggest best practices to conduct ARIA evaluations.

Efficacy evaluation: MRI is utilized to evaluate total brain volume or hippocampal volume, while FDG-PET has been used to measure metabolic activity of the brain. Recently an Amyloid imaging agent has been approved and is being utilized for drug evaluations. Site qualification including phantom imaging, image standardization and image acquisition is crucial for the success of efficacy evaluations.

In this presentation we will share our experience regarding the issues related to site reads, central independent reads, technology and risk management strategies including protocol development, site selection process, core lab selection and training of the sites and reader management.

For more information or if you are planning on attending this meeting and would like to meet with Dr. Shamsi, please contact Gloria Mercado at gmercado@rad-md.net or by phone 212-228-6994








 
RadMD's Fifth Annual ASCO Breakfast Meeting
June 02, 2013
The Fifth Annual RadMD Breakfast Session was held at the 2013 ASCO meeting on June 2nd at the Trump International Hotel and Tower in Chicago. The presentation and Q & A on Audit Reads In Oncology Trials – ODAC, FDA, And What You Need To Know was hosted by RadMD Principals Richard Patt, MD and Kohkan Shamsi, MD, PhD.

These industry experts provided insight into the current issues regarding potential new image review paradigms for Cancer Trials that had been discussed at the ODAC Imaging meeting last year. The ongoing cost and quality implications of such reviews were discussed.

Drs. Patt and Shamsi are Founders and Principals in RadMD each with over 20 years pharmaceutical clinical development experience implementing imaging in global clinical trials.

RadMD provides imaging expertise, consulting, training and physician sourcing to the pharmaceutical and biotech industries.
 
RadMD Announces 2013 Webinar Series
April 30, 2013
RadMD Experts will conduct a series of Educational Webinars throughout 2013. The first in the series, "Current Issues and Role of Imaging in Alzheimer's Disease Trials" will be hosted by Dr. Kohkan Shamsi, Principal at RadMD, on April 30th.

All programs will include a 45 minute informative presentation followed by live Q&A.

The Alzheimer's presentation will include the following topics:

Defining and Developing Imaging Strategies to Optimize Imaging Endpoints - critical in Alzheimer’s studies since MRI and PET are commonly used in AD trials to support clinical efficacy by evaluating brain volume, metabolic activity and in some cases the measurement of amyloid plaque deposits.

The significant Role of MRI in Eligibility and Safety - defining appropriate patient populations to rule out concomitant diseases or age related cognitive decline, as well as monitoring patients throughout the trial due to Amyloid Related Imaging Abnormalities (ARIA) observed in beta-amyloid antibody studies. The FDA has strongly recommended that patients recruited in all AD trials (including therapeutics not directly related to amyloid removal) should be frequently scanned by MRI to monitor and manage patients due to the occurrence of vasogenic edema, micro/macro hemorrhages and superficial siderosis.

To accomplish this in a multicenter trial is very challenging and requires prospective planning, standardization of imaging parameters across the sites, timely submission of imaging data to central reader, fast turnaround time, and quality training and selection of sites and central readers.

In this presentation, methodologies of central evaluations for eligibility, safety and efficacy will be presented and risk management strategies discussed.

Upcoming Topics to be presented throughout 2013:

Site and Central Reads in Early Development

mRECIST Criteria

Imaging in Neurological Clinical Trials

Imaging in Early Development

Risk Management in Centralized Pathology Reviews

For more information please contact Gloria Mercado at gmercado@rad-md.net
 
RadMD Presents Poster at the 2013 Association of Clinical Research Professionals Conference - Orlando, FL April 2013
April 14, 2013
RadMD Presents Poster at the 2013 Association of Clinical Research Professionals Conference - Orlando, FL April 2013
RadMD Clinical Program Manager, Jennifer Brennan, MBA, presented a poster at this year’s annual ACRP meeting in Orlando, FL April 14 -16, 2013. The topic of the poster was " Training the Blinded Reader: Clinical Trial vs. Clinical Practice”. A copy of the poster abstract is provided below.

Abstract
Imaging data collected over the duration of a clinical trial can be the key determinant as to whether or not a drug makes it to the market. Many clinical trial sponsors fall victim to the perception that the practice of radiology differs little from clinical practice to clinical trials. As a result, very little time and expense is afforded to training radiologists reading images as a part of their clinical trials. However, the reality is that reading radiographic images for the purposes of clinical trial analyses differs significantly from reading for the purpose of a patient’s diagnoses and treatment. As part of a trial, radiologists are blinded to a patient’s demographic information and medical history. They also must adhere to specific guidelines and processes in order to reduce variability throughout the reads. Radiologists reading in a clinical practice setting have very few guidelines to follow and can make decisions based on radiographic findings, clinical symptoms, and medical history. In order to bridge the gap between clinical practice and clinical trials, sponsors should focus on the selection of experienced radiologists and a comprehensive reader training and management program. Training on disease process, reading criteria, and GCP regulations should be the minimum required training for participation in any clinical trial. Data show that even after an introductory seminar on imaging in clinical trials, attendees scored 64% better on pre and post-seminar evaluations. It is expected that with comprehensive, study-specific training, reader performance can be maximized to yield higher quality data and ultimately a more efficient clinical trial.

The Blinded Reader and Investigator Training Institute (BRITI), owned and operated by RadMD, offers comprehensive education and training for Radiologists and other Physicians involved in the Blinded Read Process for Clinical Trials. BRITI offers a broad range of accredited CME courses in the area of medical imaging for pharmaceutical, medical device and biotech clinical trials. For the last few years, BRITI has partnered with ICPME to develop high-quality, well-balanced educational programs of scientific rigor and integrity that are free from commercial bias. For more information on BRITI, training of clinical trial personnel and blinded readers, please contact Gloria Mercado at gmercado@rad-md.net or by phone 212-228-6994.
 
RadMD Principal publishes in Nature Medicine
March 15, 2013
RadMD Principal, Rick Patt, MD was recently published in Nature Medicine magazine. The article entitled "Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer" was published in March 2013.

Abstract:
Jeong Heo1,17, Tony Reid2,17, Leyo Ruo3, Caroline J Breitbach4, Steven Rose2, Mark Bloomston5,
Mong Cho1, Ho Yeong Lim6, Hyun Cheol Chung7, Chang Won Kim1, James Burke4, Riccardo Lencioni8,
Theresa Hickman4, Anne Moon4, Yeon Sook Lee9, Mi Kyeong Kim9, Manijeh Daneshmand10, Kara Dubois4,
Lara Longpre4, Minhtran Ngo11,12, Cliona Rooney11–13, John C Bell4,10, Byung-Geon Rhee14, Richard Patt15,
Tae-Ho Hwang9,16,18 & David H Kirn4,18

Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n = 30). Radiologists infused low- or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes. Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses. JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity. In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14.1 months compared to 6.7 months on the high and low dose, respectively; hazard ratio 0.39; P = 0.020). JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.

1. Department of Internal Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, South Korea.

2. Moores Cancer Center, University of California San Diego (UCSD), La Jolla, California, USA.

3. Department of Surgery, McMaster University Medical Centre, Hamilton, Ontario, Canada.

4. Jennerex Inc., San Francisco, California, USA.

5. Department of Surgery, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.

6. Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Ilwon-Dong, Gang Nam-Gu, Seoul, South Korea.

7. Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Yongdong Severance Hospital, Seoul, South Korea.

8. Division of Diagnostic Imaging and Intervention, Pisa University School of Medicine, Lungarno Pacinotti, Pisa, Italy.

9. SillaJen Inc., GeumJung-Gu, Busan, South Korea.

10. Centre for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

11. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.

12. Baylor College of Medicine, Houston, Texas, USA.

13. Texas Children’s Hospital, Houston, Texas, USA.

14. Green Cross Corporation, Giheung-gu, Yongin, South Korea.

15. RadMD, Doylestown, Pennsylvania, USA.

16. Department of Pharmacology, Pusan National University, Busan, South Korea.

17. These authors contributed equally to this work.

18. These authors jointly directed this work. Correspondence should be addressed to D.H.K. (dkirn@jennerex.com) or T.-H.H. (thhwang@pusan.ac.kr).
 
RadMD Receives Cum Laude Award at RSNA 2012
November 28, 2012
Dr. Richard Patt and Dr. Riccardo Lencioni were awarded the distinguished Cum Laude Award at the 98th Scientific Assembly and Annual Meeting of the RSNA 2012 in Chicago for its poster exhibit LL-GIE 4240: "Modified RECIST (mRECIST) for Hepatocellular Carcinoma: Guidance to Image Interpretation".
 
RadMD Expands Its Imaging Expertise Services with New European Office
May 23, 2012
RadMD, LLC announces the opening of its European office to expand services to EU pharma, biotech, and medical device companies.

The new location will provide:

• A base for EU operations of consulting, training, and expert resourcing services centered on the use of imaging in clinical trials.

• An accessible location for RadMD’s expanding EU pool of expert independent radiologists and clinician reviewers

The EU office is located in Lucca, Italy, approximately 20 minutes from Pisa airport. This is the third office for RadMD, with locations in Doylestown, PA and New York City.

Reader availability can be a rate-limiting step to complete independent image reviews in clinical trials. By adding an expanded EU reader pool, RadMD can complete blinded reads faster, reducing read time and cost while maintaining quality through our proprietary tool, Reader Performance Management (RPM). Global regulatory authorities emphasize the need for transparent and standardized training in clinical trials. As with RadMD’s existing reader pool, the new EU readers will also be certified through the company’s training program, BRITI (The Blinded Reader & Investigator Training Institute). In addition, by providing blinded reading locations in both the US and EU, RadMD can leverage readers to perform rapid reviews for trials requiring fast turn around time.

“Recognizing the importance of the expanding EU drug and device markets, we are very enthusiastic about the new location and value this will bring to new and existing clients. Our unique clinical, regulatory, and development expertise provides clients with both local EU experience as well as a global perspective on imaging in clinical trials”, says Kohkan Shamsi, MD, PhD, co-founder and Principal.
 
RadMD Principals Publish in Clinical Leader
January 25, 2012
Atychiphobia: A Fear That Makes Sense When Considering Independent Reader Performance In Clinical Trials

By Kohkan Shamsi, MD, PhD, Principal, RadMD and Rick Patt, MD, Principal, RadMD

Medical imaging in clinical trials has been used as a measure of efficacy for more than 20 years. It was recognized by the FDA (FDA’s 1994 Points to Consider for Developing Medical Imaging Drug and Biologic Products and Draft Guidance 2010) that variability in evaluating trial images necessitated a more standardized, controlled and independent review process. This independent review (“blinded read”) is meant to improve the quality of imaging data evaluations from clinical trials. The performance of the reader(s) is a, and sometimes the, critical component in establishing drug or device efficacy. In this review we will discuss factors that can influence reader performance and how to actively manage readers who are blinded to clinical data to reduce bias.

Clinical practice vs. pharmaceutical practice:
In the clinical practice of radiology, a radiologist’s image interpretation is designed for individual patient management, and uses subjective terms such as “improved” or “worsening” to describe a disease process. We refer to the pharmaceutical practice of radiology, whereby readers use standardized image evaluation criteria developed to evaluate drug efficacy. And as the images they review are blinded, these readers are not influenced in their review by medico-legal or insurance issues because these images are not impact patient management. Clinical practice rarely meets the requirements to enable selection, measurement, and tracking of lesions, and may use non-standard terminology. Moreover, this standard of care clinical practice varies geographically both within the US and globally. In addition, the pharmaceutical practice of radiology, using standardized imaging efficacy criteria used in trials (eg. RECIST, IWG, etc), is not taught in radiology residency training programs.

For the rest of the article, click here

For the article posted on Clinical Leader click: Read More
 
RadMD Principal publishes in Nature
September 01, 2011
RadMD Principal, Richard Patt, MD was recently published in Nature magazine. The article entitled "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans" was published in September 2011.


Abstract:

Caroline J. Breitbach1, James Burke2{, Derek Jonker3,4, Joe Stephenson5, Andrew R. Haas6, Laura Q. M. Chow3,4, Jorge Nieva2, Tae-Ho Hwang7, Anne Moon1, Richard Patt8, Adina Pelusio1, Fabrice Le Boeuf3, Joe Burns3,4, Laura Evgin3,4, Naomi De Silva3,4, Sara Cvancic3,4, Terri Robertson1, Ji-Eun Je7, Yeon-Sook Lee7, Kelley Parato3, Jean-Simon Diallo3, Aaron Fenster9, Manijeh Daneshmand3,4, John C. Bell3,4* & David H. Kirn1*

The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumor tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically.

This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans.

1Jennerex Inc., 450 Sansome Street, 16th floor, San Francisco, California 94111, USA. 2Department of Hematology/Oncology, 801 North 29th Street, Billings Clinic, Billings, Montana 59101, USA. 3Ottawa
Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. 4University of Ottawa, 75 Laurier Avenue East, Ottawa, Ontario K1N 6N5, Canada. 5Cancer Centers of the Carolinas, 3 Butternut Drive, Greenville, South Carolina 29605, USA. 6University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA. 7Pusan National University, Jangjeondong GeumJeong-gu, Busan 609-735, South Korea. 8RadMD,712 Hyde Park, Doylestown, Pennsylvania 18901, USA. 9Robarts Research Institute,100 Perth Drive, P.O. Box 5015, London, OntarioN6A5K8, Canada. {Present address: Jennerex Inc., 450 Sansome Street, 16th floor, San Francisco, California 94111, USA.

*These authors contributed equally to this work.
 
RadMD Presents at BIO International Convention 2011
July 19, 2011
 
Blinded Reader and Investigator Training Institute (BRITI) Announces Completion of First Accredited Course on Imaging in Cancer Clinical Trials
May 20, 2011
BRITI and the International Center for Postgraduate Medical Education (ICPME) successfully hosted the first CME course on Imaging in Cancer Clinical Trials on April 16th, 2011 at the Doubletree Hotel in Philadelphia. Speakers included various pharmaceutical industry and academic experts such as Wendy Hayes, DO (Bristol-Myers Squibb), David Raunig, PhD (Pfizer), Sanjay Saini, MD, MBA (Massachusetts General Hospital), James Conklin, MD (Pharma Imaging Group Consortium), and Andrew Buckler, MS (Buckler Biomedical, LLC). Those in attendance ranged from pharmaceutical clinical trial personnel, to imaging core laboratories and independent radiologists.

"We were extremely pleased with the greater than anticipated turnout for our first live CME course, due in large part to the distinguished faculty that we assembled. We're looking forward to future courses in the US, and also in Europe and Asia." said Dr. Rick Patt, Principal of BRITI/Course Co-Director.

The full day course included 7 lectures by industry and academic experts in addition to a panel discussion, where several of the key speakers discussed current topics in clinical trial imaging and answered additional questions from the audience. The course was certified for up to 8.0 AMA PRA Category 1 Credits™ and 8.0 hours for ARRT Category A continuing education credit.

Dr. James Burke, Vice President of Clinical Research at Jennerex Biotherapeutics said the following, "The BRITI seminar helped me better understand the technical aspects and limitations of clinical trial imaging as well as the critical role played by a central radiology review. The seminar will be invaluable in determining clinical trial design with respect to radiographic endpoints."

The Blinded Reader and Investigator Training Institute (BRITI) offers comprehensive education and training through a broad range of accredited CME courses in the area of medical imaging for pharmaceutical, medical device and biotech clinical trials. For the last few years, BRITI has partnered with ICPME to develop high-quality, well-balanced educational programs of scientific rigor and integrity that are free from commercial bias.

For additional information about BRITI courses, contact Cindy Harris at charris@rad-md.net or 215-348-5644.
 
RadMD Appoints Pharma Veteran Douglas Stefanelli to New Position of Chief Operating Officer and Executive Vice President
April 11, 2011
RadMD, LLC announced today that Douglas Stefanelli has joined the RadMD Senior Management team as COO and Executive VP. Mr. Stefanelli will take over responsibility for the company’s day-to-day operating activities, and will direct the short-term and long-range planning and development to support the company’s strategic business goals. He brings with him more than twenty-seven years of experience in the pharmaceutical industry managing businesses in both therapeutic and diagnostic areas.

“Doug joins RadMD as an experienced, senior level Healthcare Executive with a track record of success. Specializing in creating new markets, developing large brands and overall business development,” said Rick Patt, M.D., one of RadMD’s Principals. “Doug will help us further build our organization and lead our commercial operations in the United States and abroad.”

Prior to joining RadMD, Mr. Stefanelli held the position of Vice President and General Manager for Bayer Healthcare where he was responsible for managing the Diagnostic Imaging business in the US. He began his career in Sales for Berlex Laboratories and later moved through increasing responsibilities in Marketing, holding positions as Director and Vice President of Marketing for both Specialized Therapeutics and Diagnostic Imaging. He has significant experience in both medical imaging and neurology therapeutics. In addition to his Marketing experience Mr. Stefanelli also managed the Business Analytics Department at Berlex as Vice President and Executive Committee member. He received his BS in Chemistry from St. John’s University.

 
RadMD to Present at FDA Bio International Convention
March 24, 2011
BIO International Convention: Drs. Shamsi leads session with Dwayne Reives, MD (FDA), Larry Schwartz MD, and Erik Pulkstenis PhD (HGS) on the Use of Imaging in Clinical Trials and Risk Management Strategies. Please see details below for more information.

Session Details
Track: Biomarkers
Session ID/Title: 87 - Use of Imaging in Clinical Development: Risk Management Strategies for Site and Independent Image Evaluations
Date: Monday, June 27, 2011
Time: 2:00 PM - 3:15 PM
Location: Walter E. Washington Convention Center, Mt. Vernon Place, NW, Washington D.C., 20001
Room: 152 A
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RadMD to Attend Several Upcoming Industry Conferences
March 23, 2011
MAGI Clinical Research Convention
May 22-25, 2011
Philadelphia, PA
Attending

ASCO
June 3-7, 2011
Chicago, IL
Attending

Bio International Convention
June 27-30
Washington DC
Presenting

RSNA
November-Dec 2
Chicago, IL
Attending

 
First Accredited Course on Imaging in Cancer Clinical Trials to be Hosted by Blinded Reader and Investigator Training Institute (BRITI)
February 08, 2011
Imaging in Cancer Clinical Trials: A One-Day Comprehensive Course – April 16th, 2011

BRITI and the International Center for Postgraduate Medical Education (ICPME) will jointly host the first CME course on Imaging in Cancer Clinical Trials. The seminar will be held on April 16th, 2011 at the Doubletree Hotel in Philadelphia and will be presented by pharmaceutical industry and academic experts. Speakers include: Wendy Hayes, DO (Bristol-Myers Squibb), David Raunig, PhD (Pfizer), Sanjay Saini, MD, MBA (Massachusetts General Hospital), James Conklin, MD (Pharma Imaging Group Consortium), and Andrew Buckler, MS (Buckler Biomedical, LLC). Additional speakers will be announced.

“We’ve designed this course for decision-makers in oncology drug development, clinical researchers and study personnel, as well as radiologists and oncologists using medical imaging to assess radiographic endpoints in the evaluation of drug efficacy. It provides attendees with a broad overview of imaging in cancer drug trials” said Dr. Rick Patt, Principal of BRITI/Course Co-Director.

Some of the topics to be covered include:
• An Introduction to Using Imaging in Cancer Trials
• Risk Management Strategies When Using Imaging in Cancer Trials
• Biostatistical Considerations and Reader Performance
• The Blinded and Site Read Processes
• Quantitative Imaging Biomarkers
• Imaging Efficacy Evaluation Criteria
• Imaging Standardization Processes

“With the increasing utilization of imaging in oncology trials has come a greater demand for formal training of pharmaceutical personnel on current concepts for applying imaging in drug trials. Regulatory agencies have also been placing greater emphasis on documented training of trial personnel. This course will provide attendees with practical and useable tools for using imaging in cancer drug trials” said Dr. Kohkan Shamsi, BRITI Principal/Course Co-Director.

The Blinded Reader and Investigator Training Institute (BRITI) offers comprehensive education and training through a broad range of accredited CME courses in the area of medical imaging for pharmaceutical, medical device and biotech clinical trials. For the last few years, BRITI has partnered with ICPME to develop high-quality, well-balanced educational programs of scientific rigor and integrity that are free from commercial bias.

For more information contact Jennifer Brennan at jbrennan@rad-md.net or 215-348-5644 or to register for this course, go to: http://courses.icpme.us/course_calendar.
 
Dr. Patt presents "Site & Central Reads in Oncology Trials: Controversies and Risk Management Strategies"
July 22, 2010
Dr. Patt presents "Site & Central Reads in Oncology Trials: Controversies and Risk Management Strategies"
at ACRP Greater Philadelphia monthly meeting, to be held at ECRI, Plymouth Meeting, PA
16 Sept 10 6pm

Contact ACRP for details.
 
RadMD attends Joint FDA-MIPS Workshop on Methods for the Evaluation of Imaging and Computer-Assist Devices:
July 14, 2010: Rockville, MD
July 22, 2010
 
RadMD presenting at FDA/Industry Statistics Workshop
21 September 2010, Washington, DC
July 21, 2010
 
RadMD to Attend:
ASCO June 4-8 2010, Chicago, IL
DIA June 13-17 2010; Washington, DC
May 05, 2010
 
On and Offsite Image Reads
Is basing drug efficacy on the site read risky business?
Excerpted from Applied Clinical Trials Online
January 01, 2010

Medical imaging in trials has been used as a measure of efficacy for more than 20 years. While the clinical practice of radiology provides sufficient information for managing individual patients, this practice varies geographically within the United States and globally. It was recognized by FDA that variability in evaluating trial images at the sites necessitated a more standardized and controlled review process, which was described in the agency's 1994 "Points to Consider for Developing Medical Imaging Drug and Biologic Products."

Read More
 
Images: Read On Site or Centrally and Independently?
Excerpted from eCliniqua
December 14, 2009
By Ann Neuer

December 14, 2009 | As clinical trial protocols call for more imaging of all types, a big controversy is brewing as to whether efficacy can be based on site evaluation of images, or if the images should be read centrally, by trained and independent professionals. Much of the brouhaha centers on oncology trials and whether sites are able to adequately identify “progression-free survival (PFS)”, an image-based surrogate endpoint that indicates whether a patient’s disease has progressed.

“Making this kind of determination requires training and consistent methodology in acquiring and interpreting the images,” says radiologist Rick Patt, principal of RadMD, a provider of “blinded reader services” and consultants for implementing medical imaging endpoints in clinical trials. Blinded read is shorthand for blinded independent central review (BICR), the form of review advocated by the Food and Drug Administration for radiographic exams used in oncology studies when PFS is the primary endpoint.

Read More
 
RadMD Offers Tips on Optimizing Clinical Trial Efficiency
November 11, 2009
DOYLESTOWN, Penn., Oct. 27, 2009 – Lengthier cancer trials and new regulations have forced pharmaceutical companies to look for new ways to minimize costs and increase efficiency. As a result, the use of medical imaging, which is currently being used in 3000 clinical trials (†), has come to the forefront. Since imaging is a very specialized field, focused training of clinical trial personnel must be conducted in a standardized fashion to optimize imaging data. RadMD LLC (www.rad-md.net), provider of consulting, training, and blinded reader services for the pharmaceutical and biotech industries, offers the following tips on making more efficient use of medical imaging during the clinical trial process.

  1. No add-ons. The FDA and regional regulatory agencies require documentation of extensive standardized training for clinical trial personnel, and efficacy and safety raters. In order for training to be effective, it needs to be part of a clinical trial plan from the beginning.

  2. Standardize – Train both onsite readers and independent reviewers. All clinical trial evaluators should be trained radiologists experienced in the clinical trial process. The on-site methodology for controlling training, testing, and ongoing reader performance monitoring should be pre-defined and well-documented.

  3. Identify site readers prospectively. When forming clinical teams for a specific site, it’s essential to identify the radiologist performing the image evaluations, particularly if imaging is an important efficacy or safety endpoint. This provides more consistent results within and across sites and less noise/variability in the results.

  4. Train enrollment readers. Radiologists reviewing images to confirm whether patients qualify for study enrollment play a critical role in assuring that each subject enrolled is appropriate to the trial. Inappropriate enrollment based on poor image evaluations affects sample size calculations, number of evaluable patients, costs, and can create ethical and legal issues. A dedicated training program and ongoing oversight of enrollment readers can maximize reader performance and ensure appropriate enrollment.

  5. Train readers for disease progression confirmation. It should be emphasized that central confirmation is not the remote practice of medicine, but is analogous to the manner in which central ECG and lab data are used. Currently, technology exists for 24-48 hour turnaround on these reads, providing an additional data point to the principal investigator when making decisions on disease progression. Readers for progression confirmation can also be the same readers as those for enrollment, but never the same as efficacy readers.

  6. Ongoing training. Reader drift happens during a trial. Re-training during a clinical trial is crucial to obtaining quality data, particularly for lengthy or concurrent trials. Training must be ongoing throughout the trial to capture new site personnel and update those that who are participating.

  7. Accept help from experts. Most companies do not have broad in-house imaging expertise or in-house imaging training programs. Seek out targeted experience to supplement your existing study-specific training and incorporate imaging training for all study personnel. A better understanding of trial imaging by study personnel (data and project managers, etc.) improves the ability to better assess imaging data quality.

† According to ClinicalTrials.gov, a U.S. government database of clinical trials, as of October 27, 2009

 
RadMD reaches 150th clinical trial
October 05, 2009
DOYLESTOWN, Penn., Oct. 5, 2009 – Completing a major milestone in its three years of operation, RadMD LLC (www.rad-md.net) announced that it has sourced readers for 150 clinical trials.

The most recent trial, conducted by ICON Medical Imaging for a leading pharmaceutical company, was designed to test the efficacy of a new treatment for metastatic kidney cancer. The trial used medical imaging to support the primary analysis of Progression Free Survival based on an independent central radiological review.

“The results of the reads showed that the drug delayed tumor growth by five months, with patients living twice as long without tumor growth as other cancer victims in the study's control arm. Ultimately, this provided the FDA with the information it needed to approve the drug,” said Ted Gastineau, president and co-founder, ICON Medical Imaging. “Quality reads are critical and delays cost money and keep drugs from getting to the people who need it most. We are confident that RadMD’s blinded readers have the skills and experience necessary to help us support our clients through the drug development process.”

RadMD sourced five radiologists with a specialty in oncology within one week of the request and helped with resources and scheduling – allowing completion of the analysis ahead of schedule. Each radiologist received formalized training and extensive testing on a variety of topics related to the use of medical imaging in clinical trials from the company’s Blinded Reader and Investigator Training Institute (BRITI)TM. All CT scans, MRIs and bone scans obtained at baseline during the treatment period and the follow-up period were sent to the independent imaging core lab at ICON Medical Imaging. 

Founded by medical imaging experts Kohkan Shamsi, MD, PhD, and Richard Patt, MD, RadMD sources clinical experts and provides consulting services for pharmaceutical, biotech and medical device trials and offers both CME-certified and non-CME courses on medical imaging in clinical trials for both on-site and offsite readers. The company’s database of 600 readers come from multiple specialties including radiologists, pathologists, oncologists, cardiologists, medical physicists, medical technologists and others. RadMD has sourced readers for trials in cardiovascular, oncology, neurology, musculoskeletal, endocrinology and sports medicine.
“CRO’s and pharmaceutical companies usually manage many concurrent trials and the availability of quality blinded readers saves money, decreases variability and expedites the trial process,” said Dr. Shamsi. “By facilitating a key component of the clinical trial process, RadMD helps pharmaceutical, biotech and medical device companies reduce clinical development time, thus getting important anti-cancer and other treatments to the market more quickly.” 

For more information about RadMD, please visit www.rad-md.net or call 267-247-5544 ext. 500.
 
RadMD First to Offer CME-Certified Education and Training For Medical Imaging in Clinical Trials
July 28, 2009
BRITI Accredited Courses Designed to Improve Quality and Accuracy of Results

DOYLESTOWN, Pa., July 28 /PRNewswire/ -- RadMD LLC (www.rad-md.net) has become the first company to offer a broad range of accredited CME courses in the area of medical imaging for pharmaceutical, medical device and biotech clinical trials.

The comprehensive education and training is offered through the company's Blinded Reader and Investigator Training Institute (BRITI)(TM). RadMD is partnering with International Center for Postgraduate Medical Education (ICPME) to obtain the CME certification.

"A huge number of clinical trials use medical imaging to demonstrate effectiveness," said Lisa Schleelein, MEd, ICPME's director of CME. "The primary goal of CME activities is to improve practice performance and patient care. RadMD is contributing to the overall quality of this process with educational activities that improve the utilization, acquisition and interpretation of medical images."

Founded by medical imaging experts Kohkan Shamsi, MD, PhD, and Richard Patt, MD, RadMD will offer both CME-certified and non-CME course modules providing clinical trial personnel with formalized training and testing on a variety of topics related to the use of medical imaging in clinical trials. The curricula were developed to reduce bias, increase data reliability and improve the accuracy of the results.

"The FDA emphasizes the role of training trial personnel but there are no standards in place to govern the use of medical imaging for this purpose," said Dr. Richard Patt, co-founder of RadMD. "Other companies in our industry use education as a marketing tool to sell their services; we recognize the crucial importance of independent, peer-reviewed validation for education and training."

The BRITI training program will offer both introductory and advanced courses on the use of medical imaging in trials, including specific evaluation methods. Customized modules for specific trials can also be developed to train pharmaceutical personnel, on-site investigators and blinded readers.
 
Read Drs. Patt and Shamsi's correspondence article in JCO
March 30, 2009
 
Pharma Veterans Launch Blinded Reader And Investigator Training Institute
Excerpted from Pharmaceutical Online
July 09, 2008
Medical imaging experts Kohkan Shamsi, MD, PhD, and Richard Patt, MD, recently launched the Blinded Reader and Investigator Training Institute (BRITI) to facilitate training for medical imaging in clinical trials. BRITI will provide... Read More
 
 
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