Clinical trial participation essential

Michael J. Fox has an excellent — and somewhat pointed — Op-Ed in today's San Francisco Chronicle in which he points out that if people want cures, they need to participate in research. He says:

Today, America is waiting expectantly for a new generation of scientific breakthroughs - in cancer, AIDS, Alzheimer's disease and, of course, Parkinson's disease. Yet we've lost sight of a critical element of any success - our own active engagement in the process.

He goes on to point out that 85 percent of clinical trials finish late because of trouble recruiting volunteers and nearly a third of all trials fail to recruit any patients at all. Case in point, Stem Cells Inc recently had to cancel their neural stem cell trial for the fatal childhood disorder Batten disease because they failed to recruit patients.

Fox goes on to say:

We're doing everything we can to identify and dismantle roadblocks that stand in the way of research progress. So far we've invested more than $230 million in research to speed new and better treatments for the disease. But we've been aware for years that dollars alone won't solve this problem. In particular, money cannot buy the critical contributions made by clinical trial volunteers.

At CIRM, that number is $1.2 billion, but the sentiment is the same. The only way research we fund can eventually become widely available therapies is through clinical trials that prove that the approach is safe and effective.

CIRM just started funding clinical trials, with a $25 million loan to Geron. We have 14 Disease Teams which are working toward clinical trials that they hope to start in 2013, and we have a new wave of Disease Teams coming down the pipeline. We look forward to working with patient advocacy groups to make sure those future trials are successful. In the mean time, if you or a loved one wants to participate in a clinical trial an excellent resource for finding those trials is the NIH clinical trials database: clincaltrials.gov.

A.A.

Global Clinical Trials: Spreading the Wealth Yields Diversity

Geoff Lomax is CIRM's Senior Officer to the Standards Working Group

In my role coordinating CIRM’s Standards Working Group, I often participate in conversations about ethical implications of participating in clinical trials. In that capacity, I recently attended the annual conference for the Association for the Accreditation of Human Research Protection Professionals (AAHRPP).

These conversations are especially important given CIRM’s Targeted Clinical Development Awards, which will be discussed at our next board meeting May 2-3 (information about that meeting will be available on our website 10 days before the meeting). Those awards will fund the clinical development of novel cell therapies derived from pluripotent stem cells.

The conference had a strong emphasis on international clinical research. One talk of particular interest was by Luc Truyen of Johnson & Johnson Pharmaceuticals. The talk titled, “Migration of Clinical Trails Outside of the United States: Is it a Problem?”, presented data on the current international clinical trial landscape.

The punch line first, Dr. Truyen’s data suggest (1) the overall volume of trial activity has grown substantially, (2) there continues to be an increase in patient enrollment and new trial sites in North America and (3) the increasing geographic diversity of trials is a measure of success.

Here are a few key points I thought were interesting:

• Cost may be a factor in limited cases. The cost of trials in the US is roughly 45% higher than China, India and Brazil – countries where increased numbers of trials are being conducted. These countries, however, also have experienced rapid growth in research and clinical capacity. Further, these countries have high incidence of diseases not common in the Untied States (e.g. hepatitis). Therefore, it is a success that they are initiating large trials to address diseases impacting their populations.
  
• Overseas trials are not a means of avoiding regulatory scrutiny.  Major trials by manufacturers for therapeutics intended for international markets are generally conducted under a FDA Investigational New Drug (IND) application. International FDA investigator inspections have quadrupled since 2002. These trials are highly regulated.
  
• Trials performed overseas support scientific validity. Many overseas trial sites are chosen for scientific reasons. Reasons include (1) there is a higher concentration of disease in the area, (2) individuals have not been treated with other therapies so the effect of the trial may be measured accurately and (3) therapy development / trials have the support of the local public health / medical community.
  
• Globalization is creating the need for therapies suitable for a diverse world.  We need international collaboration to ensure that clinical research in the U.S. and elsewhere stays applicable to the all populations.

- G.L.

Three embryonic stem cell trials and counting

We’re back after a vacation filled with news about the second ACT embryonic stem cell trial getting FDA approval earlier this week. This one is for macular degeneration. Their first trial, approved by the FDA on November 22, was for Stargardt’s macular degeneration. That brings the total to three trials testing therapies based on embryonic stem cells.

For anyone who missed the ACT announcement in the midst of New Year’s excitement, here’s a good story from the MIT Technology Review.

It’s easy to get excited about this progress, and about the additional embryonic and adult stem cell trials I hope to see approved and started in the next year. Whatever the stem cell type, progress toward new therapies is something to celebrate. At the same time I do worry about the level of hope being placed on these first three trials. More early stage trials fail than succeed, and it is likely that at least one of these early embryonic stem cell trials will fail too. That’s the whole point of testing therapies in humans — no matter how effective a therapy might have been in mice or other animals, we humans respond differently and you just never know what to expect.

The Technology Review story had this to say about the many unknowns of the ACT trial:

A number of questions remain to be answered, including how well the cells will survive in a diseased eye. Increasing evidence suggests that macular degeneration is in part an immune defect, and some people with the disease have signs of inflammation in the retina, which may it more difficult for the implanted cells to take root. "That's something animal models haven't been able to look at carefully," says Reh.

It's also not yet clear whether, if the cells do survive, they will delay or prevent further vision loss, or actually improve vision. Transplants of retinal pigment epithelium cannot replace lost photoreceptors, but they may help damaged photoreceptors function better and in turn enhance vision.

I should add that the story had a lot to say about why the trial might succeed, too. 

I’m optimistic that some of these early stem cell trials will go on to be successful, and that some of the work CIRM has already funded will be making it’s way to trials shortly. I also hope people remember that when some of these trials aren’t successful the first time it doesn’t invalidate stem cell therapies. It just means stem cells are as difficult to bring to the clinic as vaccines or cancer chemotherapeutics or any of the many other therapies that now save lives every day.

- A.A.