Opening Session Remarks, DIA 2010

Below are the introductory remarks for a panel session on mini-clini's held at the Drug Information Association (DIA) annual meeting, June 2010 in Washington, D.C.

I’m Keith Ortiz from World Class R&D and I’ll be your host for today’s session entitled 'The path towards mini-clini’s: an innovative approach to R&D effectiveness.' The following are our speakers for today:

  • Dr. David Jacobson-Kram is an associate director at the FDA in Toxicology, has been instrumental in advancing the cause of Exploratory INDs (eIND) at the FDA. He will show us how these may be used in mini-clini’s.
  • Dr. Jamie Dananberg runs global phase 1 for Lilly and will talk about mini-clini’s in research, before we even have a NME (new molecular entity).
  • Dr. Mirian Iwamoto heads up Merck’s ClinPharm for Oncology and will give example of the many different questions you can answer using mini-clini’s and eINDs.

We have David, Jamie and Mirian.

I want to thank the DIA for inviting us to talk about such a innovative (i.e., radical) idea as mini clini’s. I would like to point out the key word in the title is path. It’s a long path. There is no illusion we’ll get there fast. Today our panel will talk about some of the concrete steps you can take to start down that path.

I have just 2 slides, 8 minutes max. … 1) I’ll give a quick overview of mini-clini’s and why we care, and then 2) I’ll talk about the biggest challenge we face getting to mini-clini’s. Mini clini’s are, as the name implies, small clinical trials, 6-10 patients. Each study may have distinct protocols, patient types, procedures or even molecules (or no molecules at all). Studies have a many separate owners within the sponsor company as depicted by the many different colors, they can come from any research, clinical, medicinal chemistry, commercial, etc.

Jaimie is going to illustrate uses of min-clini's in the research area, on the left, before you even get an NME.

Why do it? Mini-clini’s are all about effectiveness. This is not an efficiency play. We set aside time-to-market+, Early Kills+ and a host of other practices that give the illusion of effectiveness (freeing up time) but not the substance.

Effectiveness means working on the right stuff. This is a question each one of us needs to ask ourselves every day in everything we do. We have to stop being comfortable with group think that picks the “right” biomarker, surrogate measure, patient profile, protocol or whatever, and then we mechanically march forward forbidding anyone to revisit past decisions+.

Each one of these little arrows asks anew the question: are these the right patients, the right indication, surrogate measures, safety, labeling, and as we’ll see … even the right molecule? On the question of selecting the right molecule, David is going to give us a nice tool, the eIND like you’ve never seen it before.

There are three measures of effectiveness: is our evidence customer-based (check), we’re all pointed in the same direction (directionally at least), and are we making sure we don’t shut down any of our options too soon. That last one’s the core of mini-clini’s. It’s really easy to fail early when you define the criteria for success so narrowly.

The Key Challenge is illustrated by The Amoeba diagram.

We all tend to stay safe within our own little circles, the nucleus, and we don’t question practices handed down to us by our predecessors. This inner circle is defined by the 3 C’s+: convention, convenience and comfort. I’m going to try, in the next 2 minutes, to get you to abandon these 3 C’s Mini-clini’s are out here in the cytoplasm. This is where we need to get for increased effectiveness in drug discovery.

… I have two monosyllabic books, both very short …

The first is called The Dip by Seth Godin. He argues instead you need to view obstacles, the circle, as being put in place to weed out the other guy. You get ahead of everyone else by finding ways out of the circle. They fall behind by letting the circle rule their lives. This applies to your personal advancement+ and to the fate of the firms where you work.

But you can’t just move out into the cytoplasm willy-nilly, our MHCII molecules will come along, pick you up as a foreign antigen and carry you to the cell surface for disposal …

So there’s another great book called The Thing by G.K. Chesterton. I have a longer quote from this so I need to read it to not mess it up …

There’s a fence or gate erected across a road. The more modern type of reformer goes gaily up to it and says, “I don't see the use of this; let us clear it away.” To which the more intelligent type of reformer will do well to answer: “If you don't see the use of it, I certainly won't let you clear it away. Go away and think. Then, when you can come back and tell me that you do see the use of it, I may allow you to destroy it.” – Chesterton, Gilbert K. (1929). The Thing

You need to know the rules in order to be allowed to break them - Old Saw. Mirian has a wonderful illustration of this, where Merck was able to get a kitchen pass from the FDA to get out of a lot of work, after using mini-clini’s in clinical pharmacology.

Finally, I have a challenge for you. Walk around the Exhibit hall and talk to folks about what it takes to make mini-clini’s a reality: IRBs, PCFs, GMP, etc. You’ll find two things. There’s a lot of wiggle room out here in the cytoplasm; and the tone of the conversation changes. The level of interest and enthusiasm goes up with something that just not 3C thinking … I did it yesterday … It’s fun.

And now on to our first speaker.

Speaker presentations, not presented here, are listed below:

  • New Options for Exploratory INDs: Why Aren’t They Being Used? David Jacobson-Kram, PhD Associate Director for Pharmacology and Toxicology, Office of New Drugs, CDER FDA, United States
  • Improving the Probability of Technical Success of Novel Targeted Therapeutics, Jamie Dananberg, MD Executive Director, Clinical Pharmacology Eli Lilly and Company, United States
  • Toward Mini-clini's: Exploratory INDs and CTAs, Marian Iwamoto, MD, PhD Senior Director, Clinical Pharmacology, Merck Research Laboratories

Further Reading