Managing Clinical Trials

Adaptive Trial Design for Phase I, Phase II

Adaptive trial design is a hot issue in the drug development community. Adaptive conferences and web seminars abound, and suddenly, every consultant or vendor to the industry has become an adaptive expert. The FDA and EMEA are also much more receptive to adaptive trials than they were a few years ago. 

However, the picture is a shade different from what the industry had expected. Originally, much of the focus was on adaptive phase III trials as well as on seamless phase II/III trials. Those are, indeed, successfully being implemented today. But the real action is in phase II dose-finding trials and even in phase I trials for safety.

In today’s new issue of Peer Perspectives in Oncology, Medelis talks with Ranganath Nayak, Ph.D., the CEO of Cytel, Inc., about the benefits, opportunities, and challenges presented by adaptive trial design in phase I and phase II studies. Cytel has designed more adaptive trials for industry sponsors than any other service provider and in virtually every therapeutic area, including medical devices.

Dr. Nayak begins by discussing why adaptive trial design is gaining so much momentum in early stage studies. "First, adaptive trials are most helpful when you do not know enough at the beginning of a trial to design it with confidence," he says. "This is much more likely to be true in phases I and II than in phase III.  

"Second, the best way to make expensive phase III trials more successful is to do more thorough work in phases I and II," he continues. "Getting the dose right through well-designed phase I and phase II trials is the best way to maximize success in phase III, which then leads to a higher rate of NDAs. “

Dr. Nayak offers insight and expertise on a variety of issues surrounding adaptive trial design, including:

• Commercial, ethical, and budgetary benefits of the adaptive trial model;
• Statistical and data issues;
• Changing to the adaptive model across multiple sites;
• Safety issues to consider;
• Budgeting for an adaptive trial;
• Dealing with independent decision-making bodies;
• Patient consent and communication issues;
• Medical supply logistics;
• Other best practices and planning issues.

Download the abstract here; you’ll also gain access to the other issues in the series, and we’ll notify you of future publications as well.  

ASU launches new Master of Science, Clinical Research Management program

Innovative online program provides convenient specialty training for nurses, physicians & health care professionals

Medelis President and CEO Bob Bosserman serves on the advisory board for Arizona State University's Center for Healthcare Innovation & Clinical Trials, and we're pleased to share this information about their Master of Science in Clinical Research Management, a new online 33-credit degree program for working professionals around the globe.

The field of clinical research is changing dramatically, and this program prepares students to be innovative industry leaders in specialized positions including regulatory affairs, clinical research operations, auditing, and monitoring. The curriculum includes

• Emerging technologies and methodologies
• Clinical research project management
• Study design
• Trends in global trial operations
• Regulatory requirements for healthcare-related product development
• Clinical research process improvement techniques

Students can complete the degree online in 17, 24, or 42 months, and the program culminates in a 6-credit capstone project designed to advance the field of clinical research.

ASU is currently accepting applications for Fall 2010. To learn more and apply, please visit the ASU College of Nursing & Health Innovation web site.

Mouse Hematology: A Laboratory Manual

Mike McGarry, Ph.D., our Vice President of Preclinical Studies, along with his Arizona Mayo Clinic colleagues Cheryl A. Protheroe and James J. Lee, has just authored a new book, Mouse Hematology: A Laboratory Manual, now available for pre-order from Cold Spring Harbor Laboratory Press (ships in December):

http://tinyurl.com/mousehematology

Dr. McGarry, a preclinical research scientist with over 35 years of experience generating animal-based data, leads preclinical program design, management and execution on behalf of Medelis’ biotech clients around the world.

Here’s the description from CSH Press:  

The mouse has become a standard laboratory model organism, particularly for the study of hematopoiesis, the immune system, and inflammation. Although laboratories studying stem cells, blood, and blood-forming tissues have assimilated many new molecular diagnostic methods, the identification of cell lineages through classical light microscopic techniques is often poorly understood and practiced. Mouse Hematology presents a concise review of conventional methods for the preparation, enumeration, and microscopic examination of blood and blood-forming tissues of the laboratory mouse. Along with a short laboratory manual featuring detailed protocols, Mouse Hematology includes a DVD of short video demonstrations of the techniques and a poster of blood cell types for easy identification at the microscope. These rapid, inexpensive assessments can save valuable time and resources essential to the design, development, and interpretation of experiments.     

Contents include:

1. Collection of Peripheral Blood
2. Counting Red Blood Cells, Platelets, and Viable Nucleated White Blood Cells
3. Peripheral Blood Films and Cytospin Preparations
4. Cell Differential Assessments of Peripheral Blood Films
5. Preparation of Bone Marrow for Microscopic Examination
6. Cell Differential Assessments of Bone Marrow

The book also includes 8 videos on an accompanying DVD:

1. Venous Access for Blood Film Using Lateral Tail Vein
2. Venous Access for Blood Film Using Tip of Tail
3. Blood Film
4. Staining with Coplin Jar or Carriages
5. Coverslip
6. Cytocentrifuge Procedures
7. Surgical Exposure of Femur
8. Brush Smear of Marrow

To preorder, visit the CSH Press website: http://tinyurl.com/mousehematology.

Dr. Alan Sandler, Dr. James Cassidy Join Medelis' Medical Advisory Board

We’re pleased to announce more company news today:  Two leading oncology researchers, Dr. Alan Sandler of Portland, Oregon and Dr. James Cassidy of Glasgow, Scotland, have joined our Medical Advisory Board.  

Alan Sandler, M.D. is a Professor of Medicine in the Division of Hematology & Medical Oncology, Department of Medicine, at Oregon Health & Science University in Portland, Oregon. Board-certified in Medical Oncology and Internal Medicine, he serves as the Division Chief of the Hematology & Medical Oncology Division and holds the DeArmond Chair for Clinical Cancer Research. He specializes in cancer and blood disorders with a special interest in lung cancer, and he is widely considered a key opinion leader in the development of targeted therapies in the treatment of thoracic malignancies.

Dr. Sandler is a member of the American Society of Clinical Oncology and the Eastern Cooperative Oncology Group, where he serves as the Co-Chair of the Thoracic Committee. 

James Cassidy, MBChB, MD, MSc, FRCP is a leading researcher in anti-sickness compounds and innovative approaches to drug-resistant tumors. Dr. Cassidy is a Professor of Oncology and heads the Medical Oncology Department and the Division of Cancer Sciences & Molecular Pathology at the University of Glasgow, Scotland. He heads the Centre for Oncology and Applied Pharmacology (COAP) and has his own Cancer Research UK (CRUK) lab based program exploring methods for gene and drug delivery. He also heads the Glasgow Experimental Cancer Medicine Centre (ECMC) which is focused on Good Laboratory Practice (GLP) quality assured assessments of molecular markers, pharmacodynamics and pharmacokinetics of novel agents at the clinical/lab translational interface.

On the clinical side, Dr. Cassidy runs a service for colorectal cancer patients and has a major commitment to early phase clinical studies of innovative therapies. 

In our formal news release, Medelis president and CEO Bob Bosserman says, “Medelis is very privileged to add Dr. Cassidy and Dr. Sandler to our distinguished group of expert advisors. They strengthen our ability to provide clients with cutting-edge expertise and assistance in the development and advancement of personalized therapies, which will ultimately help improve the treatment options for clinicians.  They also further strengthen our relationship with the clinical research community that directly cares for cancer patients and closely understands their needs.”

“Both of these physician/researchers can now bring their clinical experience to bear on the unique study design and management issues that our biotechnology and pharmaceutical clients face in the oncology drug development process,” Bosserman adds.

You can find Dr. Sandler’s full bio here and Dr. Cassidy’s bio here.

Medelis expands CRO services to medical devices, welcomes Dr. Inder Makin

Today we’re pleased to announce that we're expanding our CRO services to the medical device industry under the guidance of Inder Makin, M.D., Ph.D., who is joining us as Vice President, Devices & Radiological Health. 

Dr. Makin has more than 20 years of experience developing "concept to clinic" healthcare technologies in both academia and industry.  He has developed medical ultrasound-based research programs at various institutes, taking concepts (including catheter-based devices for intravascular thrombolysis, transdermal drug delivery devices and non-invasive and intracorporeal tissue ablation devices) through feasibility and launch. 

Dr. Makin’s unique combination of medical and biomedical engineering expertise enables him to assist our clients in effectively developing and refining new device solutions for patients.  He will also provide invaluable guidance in helping obtain marketing approvals for successful commercialization. 

Medelis will support device manufacturers throughout the product life cycle including early design and prototyping, simulation, preclinical and phase I-III clinical studies, and regulatory/marketing approval. 

You can read Dr. Makin’s full bio here. If you'd like to learn more about our services for the medical device industry, please contact us today.

Big pharma tackles patient recruitment challenges, but we have a long way to go

Yesterday, Pfizer and Private Access, a search technology firm, announced that they’re joining forces to create an online community aimed at increasing awareness and participation in clinical trials.

According to this Fierce Biotech article, "Nearly 85 percent of patients in a recent survey stated they were unaware that clinical trials were a possible treatment option, and 31 percent of physicians surveyed did not refer patients to trials due to, among other things, lack of information."

The statistics for cancer clinical trials are even more dismal.  Earlier this month, the New York Times’ "Lack of Study Volunteers Hobbles Cancer Fight" reported the well-known statistic that only 3 percent of cancer patients participate in trials for new treatments.  As the article explains, “There are more than 6,500 cancer clinical trials seeking adult patients, according to clinicaltrials.gov … but many will be abandoned along the way.”

In fact, only half of the trials sponsored by the National Cancer Institute fail to reach the minimum needed for a meaningful result, according to cancer researcher and health economist Dr. Scott Ramsey and his colleague John Scoggins in an editorial in the September 2008 issue of The Oncologist. Furthermore, more than one in five NCI trials failed to enroll a single subject.

Their conclusion:  “Research sponsors, researchers, and journal editors should redouble their efforts to encourage publication of registered clinical trials in oncology.”

As patient recruitment costs continue to skyrocket as enrollment statistics decline, we couldn’t agree more.  Rapid, efficient patient recruitment is, without a doubt, a major barrier preventing our industry from successfully delivering promising new treatments to patients.

Links to the stories:

• Fierce Biotech article about Pfizer and Private Access
• Editorial in The Oncologist
• Lack of Study Volunteers Hobbles Cancer Fight (New York Times)

IRB Selection Tips from ClinPage

Suz Redfearn at ClinPage recently posted an excellent article about IRB selection, and it’s valuable reading for sponsors or CROs who are struggling with their IRB. 

“Choosing an IRB is an issue that doesn’t often get a lot of attention, but if poorly done it can cause a lot of delays for a sponsor and a CRO,” says Sue Hocker, a consultant who provides an in-depth look at the issues throughout the article.

Pointers include:

• Check the U.S. Dept. of Health & Human Services’ Office for Human Research Protection Institutional Review Board of Registry.  Make sure the IRB you’re considering is listed and violation-free.
• Interview the IRB with an eye on the issues that can delay your study.
• Evaluate the IRB’s capacity and pay close attention to the number of high-risk trials they’re handling.  “When a megatrial comes due for follow-up reviews—an all-hands-on-deck situation—the IRB’s smaller trials may be slighted,” Redfern writers.
• Make sure the IRB completely understands the protocol and is experienced in your therapeutic area.
• Understand the IRB’s regular meeting schedule, project management process, and document management system – surprises can pop up here and cause unexpected delays.

Check out the complete article (highly recommended) here.

"Context of vulnerability" and its role in targeted drug development

Renowned cancer researcher Dr. Daniel Von Hoff and his team at TGen are fervent believers in a new approach to developing novel therapies for patients with pancreatic cancer. Their rationale, dubbed “context of vulnerability,” is a powerful new drug development paradigm that’s generating impressive results.

Medelis has just published a free downloadable interview with Dan (download it here) as part of our “Peer Perspectives in Oncology” series.  In the abstract, Dan explains how this model has already led to promising discoveries and is changing the future of oncology drug development. 

“Context of vulnerability,” a term coined by TGen’s Spryo Mousses, Ph.D., refers to the genetic configuration in a patient’s tumor that makes it susceptible to a specific drug.  “Context of vulnerability provides the genetic rationale for a targeted therapy,” Dan explains.

In the abstract, he provides examples of context of vulnerability in use.  “One way to establish the context of vulnerability is to work backwards from the result,” he says.  “For instance, in a phase I or phase II trial, you treat a certain number of patients, and when someone responds, you have to ask yourself, ‘Why did that patient respond?  What was the vulnerability in this specific tumor or patient?’  The patient either had a genetic lesion or tumor stroma that was susceptible to the drug in some way.”

Dan explains that context of vulnerability can improve a sponsor’s chance of seeing efficacy during an early-stage trial with a much smaller n.

“If you let context of vulnerability guide drug development, you would put only those patients who have the appropriate susceptibility to the drug on trial,” he emphasizes.  “It’s essentially how Herceptin® got approved with an n of 480.  If they hadn’t pre-selected patients for the context of vulnerability, estimates say that it would have taken about 23,000 patients to get the drug approved.”

Throughout the interview, Dan addresses many of the questions and opportunities presented in this model:

• How context of vulnerability provides a genetic rationale for a targeted therapy;
• How to establish a patient’s context of vulnerability;
• How using context of vulnerability to guide drug development can improve your chance of seeing efficacy with a much smaller n;
• Incorporating context of vulnerability as the oncologist’s “sixth vital sign;”
• A case study of context of vulnerability in use and how it improves patient care and new agent development;
• The gap between known contexts of vulnerability and available therapeutics;
• How CMOs can flip their drug development planning to leverage this approach;
• Feedback from the FDA, national and international groups;
• Targeted therapeutics and the future of oncology.

The abstract is the fifth in Medelis’ “Peer Perspectives in Oncology” series, and you can download the entire series here.  You’ll receive email notices when future issues are published as well.