Managing Clinical Trials

Can the internet fuel drug development?

What happens when some cancer patients become frustrated with their treatment options?  They search for a cure on their own. Some raise money to build awareness; others donate to further research.

Dr. Jay Tenenbaum, an e-commerce pioneer who is battling melanoma that spread to his liver, took a different approach:  he created a company to allow patients to discover new drugs with the help of the internet. 

CollabRx builds and operates "virtual biotechs" for people seeking cures on their own.  The CollabRx platform connects researchers to one another and to a network of scientific services.  Wealthy individuals, foundations and patient groups can join in to financially support specific research activities.  The system encourages researchers to share information and collaborate, going against the grain of the traditional scientific process.

While it’s unclear whether the concept will work, CollabRx highlights how the internet is starting to affect drug development.  Some of our sponsors are starting to recognize how the internet can help them recruit patients for their trials.  While pharmaceutical companies may be slow to pick up on the power of the web, patients seem to be a few steps ahead.

Amy Dockser Marcus provides a detailed look at CollabRx in yesterday’s Wall Street Journal.  She also provides excellent tips for patients who want to make a difference in the search for a cure.

Insight: Preventing a Preclinical Dead End

Oncology preclinical studies are commonly viewed as straightforward investigations run exclusively by researchers.  Tasked with finding molecules that stop cell growth, researchers often operate independently without true integration with the preclinical, regulatory and clinical teams.

Dr. Mike McGarry, a preclinical research scientist with 35 years of experience generating high quality animal-based data, advocates for a more synergistic approach.  In an upcoming issue of "Peer Perspectives in Oncology," he weighs in on the typical preclinical process and shares insight that can help CMOs extract more useful information that aids drug development and speeds overall progress to phase I.

One of the big issues Dr. McGarry commonly sees is a chasm between a sponsor’s preclinical and clinical teams.

"Preclinical researchers are extremely technical and scientific; they’re focused on microscopic details of various tissue or organ side effects," he explains.  "On the other side, the CMO is pushing to move a drug forward while managing costs to meet the company’s targets.  That forward momentum can create friction with the conservative, tentative nature of the research scientist who is watching the nuances unfold and has perhaps a very different perspective on the trial."

Without close communication and integration, preclinical experimentation can lead to a regulatory brick wall, a scenario no CMO wants to experience.

"I’ve spent most of my career in preclinical experimentation, and it's an expensive funneling process," he continues.  "You start with thousands of compounds and eventually narrow it down to the one that warrants close scrutiny, hopefully making it into clinical study and application. As you’re narrowing the field, the preclinical team also has to focus on the end goal or you can easily end up in a place that has no utility."

For a CMO, the answer is to get more involved in the preclinical process to gain insight, lead the study direction and prevent the silo effect from derailing a promising drug.

"There needs to be ongoing, seamless communication and integration among the clinical, regulatory and pre-clinical teams," he adds. "Communication affects the quality of results to be reported and thus the usefulness of the data.  Each team should be actively involved in feasibility dialogue at each step in the study."

The complete interview is one of several slated to be published this summer.  You can sign up to be notified via email here.   

Dan Von Hoff discusses "The Complete Phase Ib"

Medelis has published a free new downloadable abstract, "The Complete Phase Ib: An Approach to Getting to Phase II Faster," an interview with renowned oncology investigator Daniel D. Von Hoff, M.D. 

"The typical phase I approach is essentially serial drug development, which involves running multiple separate trials,” Dr. Von Hoff explains at the beginning of the interview.  "Each site at each trial adds a layer of time, cost, and management oversight. What I call 'the complete phase Ib' is a simple solution that essentially tests the various drug combinations in one phase Ib with multiple arms run in parallel.

"For example, assume you have good preclinical data on a single agent that may be more effective in combination with another agent—for example, a monoclonal antibody plus gemcitabine (GEMZAR®)," he explains. "Most Chief Medical Officers anticipate that the pivotal clinical trials will be standard therapy with or without the new drug, and they prepare for that eventuality by conducting a phase I trial of the combination. Typically, this involves launching five, six, or sometimes more combination phase I trials. Each trial has to be negotiated and managed separately, and each must have its own protocol, adding layer upon layer of cost and effort.

"The strategy I'm suggesting eliminates all these separate serial trials because it puts the combinations into one phase Ib trial."

Dr. Von Hoff offers a detailed look at this approach and the many benefits to sponsors, patients, and investigators, including:

• Patient accrual and treatment benefits
• How the approach can "rescue" patients
• Dosing strategies
• Logistical considerations
• Cost and timing considerations
• Effects on phase II studies
• Reactions from the FDA investigators, sponsors and patients

The abstract is the second in Medelis' "Peer Perspectives in Oncology" series.  In the first issue, "Patient Safety in Clinical Trials," Dr. James Gourzis discusses recent issues in patient safety and the role of sponsors, CROs, IRBs, DMCs and the FDA in ensuring patient safety in future clinical trials.

You can download each of the interviews here.  You’ll receive email notices when future issues are published as well.