Managing Clinical Trials

IRB Selection Tips from ClinPage

2009-02-24T12:35:21-07:00

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

2009-02-17T09:03:19-07:00

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.

The "Lost Opportunity” in Phase I Oncology Trials

2008-12-22T08:30:00-07:00

Cancer drug developers traditionally use the phase I trial solely to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of a drug. Today, we’ve published a free new downloadable abstract, "The Lost Opportunity in Phase I Oncology Trials," an interview with renowned oncology investigator Daniel D. Von Hoff, M.D. In the interview, Dr. Von Hoff advocates for a phase I approach that looks beyond toxicity and gleans meaningful efficacy data, creating a more compelling rationale for further investment and improved patient care.

“A Chief Medical Officer looking at the phase I typically sees it as a toxicity trial, not a therapeutic trial, because of course it is not randomized,” Dr. Von Hoff explains. “But we - doctors at the bedside and the patients themselves - do not see it that way. We are looking for improvement and survival. [The phase I] is an opportunity to look for therapeutic effect as well because it might just be there.”

Dr. Von Hoff supports an additional analysis that uses a cancer patient as his or her own control. Rather than solely relying on the traditional data captured in normal phase I protocols, he recommends measuring the tumor’s “time to progression” on the current drug versus the tumor’s “time to progression” on the patient’s previous treatment. This data — time to progression on each drug — should be systematically tracked in the protocol so it becomes part of each patient’s data bank.

“I have never seen a CMO plot time on a new drug versus the time on a just-prior therapy to build a story for raising money,” Dr. Von Hoff continues. “This idea of using the patient as his or her own control is a lost concept in drug development. Dr. Bob Temple at the FDA, an icon in clinical trial design, calls it a lost art. He’s referring to the ability to document changes in the natural history of a patient’s tumor, and how this information can give you a sense of whether the drug will work.”

“If you treat 30 patients and 30% stay on a new therapy for a longer time than the just-prior drug they had progressed on, then that would justify a deeper investment,” he explains. “Patients’ tumors grow at an inexorable, ever-quickening rate. If you find an agent that can taper that growth, then it is probably doing something and should be pursued.”

“There is no question in my mind that, if a CMO started comparing time on new drug versus time on just-prior therapy, the rewards are there – both for the patients and for the progression of the drug. All it takes is a more proactive approach to the phase I. It is so simple yet I have never seen a CMO adopt this.”

In the abstract, Dr. Von Hoff answers many questions about this “lost art” in the phase I trial. Download the full issue here; you’ll also gain access to the other issues in the series, and we’ll notify you of future publications as well.

Dr. Dan Von Hoff honored at Governor’s Celebration

2008-11-25T08:47:22-07:00

Our colleague Dan Von Hoff, M.D., a founder and shareholder of Medelis and the chairman of our medical advisory board, was recently named Arizona’s ‘Community Service Leader of the Year’ at the 2008 Governor’s Celebration of Innovation in Phoenix.

A member of the NIH’s National Cancer Advisory Board, Dr. Von Hoff is a world-renowned cancer researcher who has devoted more than 35 years to two primary goals: identifying the best new anti-cancer agents to treat patients and curing pancreatic cancer. He has published more than 540 scientific papers, more than 130 book chapters, and nearly 950 scientific abstracts. He also holds a dozen patents for new anti-cancer agents and medical devices. (Full bio here.)

The annual award honors an organization or individual who contributes to Arizona's technology industry through relentless community involvement, leadership, visibility and excellence in economic development activity.

Medelis will soon publish a new issue of “Peer Perspectives in Oncology” featuring an in-depth interview with Dan about oncology phase I trials. He describes how Chief Medical Officers can design better phase I trials to glean meaningful efficacy data by using the patient as his or her own control. He further explains how a CMO can gather evidence showing a drug changes the natural history of a patient’s disease, demonstrating improved care and a stronger case for moving a drug into phase II.

In our summer 2008 issue, Dan offers a detailed look at “The Complete Phase Ib,” a clinical trial structure that creates rapid accrual rates, substantial economies of scale and significant time savings for sponsors versus the traditional sequential approach.

You can download past issues and sign up to be notified of future publications here.

Personalized Genomics: The First Report of a Cancer Genome

2008-11-13T09:21:22-07:00

As reported by the New York Times last week, Washington University recently completed a study that decoded the entire genome of a cancer patient. The patient, a woman in her 50s who died of leukemia, became the first cancer patient and the first female to have her entire genome decoded.

To protect the patient’s identity, the data will be available to scientists only.

While the finding won’t help patients right away, the controversial project, funded primarily by a private donor, could open the door to entirely new approaches to treat cancer.

A cancer expert not involved with the study, Dr. Stephen Nimer, chief of the hematology service at Memorial Sloan-Kettering Cancer Center, called the research a “tour de force” and the report “a wonderful paper.” He said the whole-genome approach seemed likely to yield important information about other types of cancer as well as leukemia.

While scientists have debated the validity of sequencing the whole cancer genome, the study was possible due to recent advances in technology that have made it easier and cheaper to analyze 100 million DNA snippets.

Dr. Richard K. Wilson, director of Washington University’s Genome Sequencing Center and the senior author of the study, sees a bright future for DNA sequencing. “That’s personalized genomics, personalized medicine in a box,” he said. “It’s holy grail sort of stuff, but I think it’s not out of the realm of possibility.”

Dr. Wilson said he hoped that in 5 to 20 years, DNA sequencing for cancer patients would consist of dropping a spot of blood onto a chip that slides into a desktop computer that produces a report suggesting which drugs will work best for each patient.

Some feel that this study signals a change in the oncology drug development landscape. If personalized medicine for oncology becomes a reality, it could signal the end of the “one-size-fits-all” oncology blockbuster drug. Patient survival rates should increase, because cancer patients and oncologists will have a greater selection of drugs and more data to predict efficacy.

The real change will be in the drug development process: Biotech and pharma will need to create more varieties of drugs that affect different genomes. Efficacy rates should improve, but each drug will treat far fewer patients. Clinical trials will be smaller and faster, as many of the drugs should receive FDA Fast Track and/or Orphan Drug status.

That puts quite a burden on oncology drug developers. Not only do they need to shoulder the additional costs of creating more drugs (that will produce lower revenues per drug), but they will also have to create more efficient trial designs to handle the larger number of smaller, quicker trials for each drug.

One way to accomplish this is to run phase I and/or phase II trials in parallel instead of running multiple separate trials. For a deeper discussion of this strategy, check out Dr. Daniel Von Hoff’s 'The Complete Phase Ib' Insider Abstract.

But the biotech and pharma industries will adapt. If the personalized genomic predictions are correct, the burden will be worth it when powerful treatments are developed to match common genomes.

Excellent cancer discussion on the Diane Rehm show

2008-11-05T07:23:00-07:00

Yesterday morning’s Diane Rehm Show on NPR featured an excellent, detailed discussion about cancer and genomics research in terms that are very understandable for patients, families, and the general population. Diane’s guest, Dr. Bernadine Healy, is the health editor of U.S. News & World Report, the former director of the National Institute of Health, the former director of the American Red Cross, and the author of “Living Time: Faith and Facts to Transform Your Cancer Journey.”

In the opening of the “New Approaches to Treating Cancer” segment, Dr. Healy, a cardiologist, touches on her own personal journey with cancer; she was diagnosed with a malignant brain tumor on Valentine’s Day 1999. “One of the sad things about cancer is that so often it hits in the prime of life,” she explains. “Virtually everybody is touched by cancer, either directly themselves – about 40% of people – but also through their families. Cancer is a family effort; it’s a family disease.”

They go on to discuss, in nontechnical terms, how the mapping of the human genome offers the possibility of a personalized approach to diagnosing and treating the disease, along with the latest developments in the war on cancer.

If a family member or friend is learning about cancer, this segment is an excellent resource. Here are several links you can share:

You can listen to the broadcast via Windows Media Player or Realplayer here.
Download the MP3 here.
Subscribe to all of the shows via podcast here.

Discover clinical trial management, biotech and pharma resources on document-sharing web sites

2008-11-04T08:26:56-07:00

We’ve recently begun using two web sites that allow users to share conference presentations, seminar materials, educational tools, research data and more. The first, SlideShare, is like YouTube for PowerPoint and PDF presentations; the second, Docstoc, allows users to share PowerPoint as well as Excel, Word and other document types.

We’ve uploaded several of our popular Insider Abstracts so that industry professionals, students and researchers around the world can discover, download and share them with colleagues. For example, here is our “The Complete Phase 1b” interview with Dr. Dan Von Hoff; you can scroll through all of the slides below. To download it, just click through to the SlideShare web site.

View SlideShare presentation or Upload your own. (tags: pre-clinical medelis)

Here's a second abstract that features Dr. James Gourzis discussing patient safety in clinical trials:

View SlideShare presentation or Upload your own. (tags: patientsafety clinicalresearch)

We used this presentation to promote our new Medelis Europe division during the recent BioPartnering Europe seminar in London:

View SlideShare presentation or Upload your own. (tags: cro medelis)

These services are excellent tools for conferences, seminars, researchers, companies and far-flung groups to share and discover new data and educational materials. We’ll continue to publish our abstracts via these services and encourage you to add us to your network and share your own materials as well.

On SlideShare, you’ll find our Insider Abstracts at www.slideshare.net/medelis, and we’ve started a group at www.slideshare.net/group/biotech-pharma. Our Docstoc account is www.docstoc.com/profile/oncologycro.

Medelis expands CRO services into Europe, appoints Dr. Deirdre Tessman to run the operation

2008-10-09T12:57:25-07:00

We’re very pleased to announce that our colleague Deirdre Tessman, Ph.D., has officially joined our organization to lead our new Medelis Europe division as its Managing Director. She’ll also be re-joining her longstanding former colleagues Dr. Daniel Von Hoff, Dr. Skip Burris, and Dr. Mace Rothenberg, all members of Medelis' Medical Advisory Board.

Deirdre brings ten years of experience managing European studies, an extensive understanding of European regulatory requirements and a deep familiarity with all phases of clinical development to Medelis clients who wish to complete the regulatory requirements of the European Community for their therapies and devices.

Beyond her European expertise, Deirdre brings more than 30 years of worldwide drug development and regulatory experience to our organization. She’s directed all phases of pharmaceutical development from research through drug approval and marketing with additional expertise in the startup and turnaround of pharmaceutical companies.

Medelis Europe delivers complete oncology drug development services from preclinical through phase III. European, U.S., and Asian sponsors looking to bring drugs to the U.S. & European markets can now take advantage of Medelis’ full service offering, which now includes EDC for phase I studies; internet-based patient recruitment; and integrated preclinical studies aligning the preclinical, regulatory and clinical teams.

Please join us in welcoming Deirdre – here is her contact information. You can also find a formal announcement about her appointment and background here.