Monday, November 24, 2008

Economic Realities Continue to Hit Biotech Development

"Unprecedented" Biotech Bankruptices Erupt Amid Financial Crisis -- at Bloomberg

Biotech Firms Face Cash Shortage -- at USA Today

More Biotech Bankruptices on the Horizon -- at Fierce Biotech

Zagats for Clinical Trial Sponsors and CROs

Living in Manhattan years ago, Zagats defined how we found restaurants. This was Web 2.0 before the Internet -- relying on feedback from other diners to find the "best" restaurant.

Today the spirit of user ranking and feedback defines Web 2.0 -- TripAdvisor tells us which hotel is best, Epinions which product is best, etc.

We are also seeing the Zagat spirit in healthcare. Enter your doctor's name in Google and the first matches are likely all physician and hospital rating sites -- HealthGrades, Vitals, RateMDs. Even Zagats has entered the fray of rating doctors.

So how far could we be from sites where investigators and patients can post reviews and rankings for clinical trial sponsors?

Some groups such as CenterWatch have a history of surveying sites to identify top rated CROs and sponsors. But moving from a controlled survey to the "wild west" of Internet reviews and postings will be a different world. Same too for inviting feedback from patients.

If this seems unrealistic, that is probably what the venture capital community used to believe. No entrepreneur would ever dare to post ratings and reviews of interactions with VCs while seeking funding? And then came, disrupting and nudging a long-standing power balance.

Today many are addressing the shortfall in number of investigators by looking for sites around the world, and addressing the challenges in patient recruitment by increasing trial-related advertising spend.
Perhaps such a review website would be good for drug development -- a site where investigators and patients were posting their feedback and ratings may force the industry to identify and address the roots behind the problems.

Freakonomics of Drug Development

In their best-selling book Freakonomics, Levitt and Dubner look at the world through the lens of economics and demonstrate how incentives (how people get what they want or need) are the root of most everything around us.

So what are the Freakonomics of drug development? Where are the incentives?

Here is a good starting question -- If you work at a "sponsor" is the goal of your company to make medicine or to sell medicine?

I would argue that if you are at a start-up biotech, you are there to make medicines. Your company likely aspires to get a drug into clinical trials, but it is unlikely they would still own the drug by the time of registration and equally unlikely the company would transform into sales & marketing.

If you are at a large pharma, I would argue your company is there to sell medicine. To confirm this, look no further than the revenue cliff ahead for most pharma as patents expire. The anticipated drop in sales is what drives most current decision-making.

So where are the incentives for those in development? Does your company reward for new project starts (regardless of ultimate project value)? Does it reward for killing a project early? Does it reward for innovation and risk-taking?

If your company is ultimately seeking to bring new approved medicines to patients and the marketplace as quickly and safely as possible, it would seem most of these incentives are misaligned.

Monday, November 17, 2008

Web 2.0 … Health 2.0 … Research 2.0?

Web 2.0 showed us how social networking, communities, and collaboration could make the Internet a more engaging and interactive experience – think Facebook, Flickr, and YouTube.

Health 2.0 takes a page from the Web 2.0 playbook to enable the health consumer (formerly known as "patient") to also become engaged in their health and wellness. Here we have on-line support groups and condition-specific forums. We have our health information becoming accessible with tools to make it actionable (via personal health record offerings from
Google Health, Microsoft HealthVault, and others). We even have on-line forums for medical professionals, enabling physicians to have peer-to-peer social networking (Sermo).

Health 2.0 brings great potential for improving individual wellness as well as public health, but what are the implications for clinical research? Should we anticipate “Research 2.0”?

In its most primal form, Research 2.0 could mean new ways to find patients that may be interested and eligible for clinical trials.
Inspire builds strong on-line communities of patients around specific conditions and diseases, then makes clinical trial matching available to these communities.

At another level, has demonstrated the willingness of patients to share personal health information and experiences for the benefit of their patient communities. Registered users (and there are several thousand) share functional status, medication and supplement use, and other interventions. As a result of this information sharing, PatientsLikeMe has found a novel Research 2.0 tool – patient-initiated research.

The patients in this community wanted better data to understand if
Lithium is of benefit to patients with ALS. In the spirit of “Research 2.0”, these patients are now sharing their experience – via structured, quantitative data – and creating a dataset including the clinical experience of several thousand ALS patients.

A future with Research 2.0 brings opportunity and risk. Patients may be recruited for trials through communities, but patients may also freely create a discussion forum within a community to discuss experience within a particular trial. Imagine a significant percent of the subjects in your randomized and blinded trial virtually “talking” with one another and exchanging experiences and observations. This is a reality one needs to anticipate.

Physicians have long been concerned about Web 2.0, with patients seeking health information on-line and the risks of user-generated content. But there is more to worry about than whether
Google can get a diagnosis correct.

Pharma has its own fear of patients in a world of Web 2.0, with concerns over inappropriate identification of safety signals (FYI, any known adverse experience linked to a specific drug that can be traced to an identifiable patient with an identifiable reporter
must be reported to FDA).

The dialogue can not be stopped, and so risks (and potential benefits) must be understood. Some (
see BMS and Novartis unrestricted grants for social networking) are already seeing this potential . Our patients are talking and the waiting room chatter is now global – are we ready to listen?

Images: Flickr

Will Change in Washington Bring Change in Clinical Research?

On January 20, 2009 change will come to Washington. Will a new resident in the White House have implications for drug development? Here are a few areas of possible impact:

Investments in Health Information Technology
Both Obama and McCain featured increasing investments in Health Information Technology as part of their healthcare reform proposals, and the recent Max Baucus reform proposal continues the trend. While the intent from the politicians is to decrease medical costs, reduce errors, and improve quality, there is great potential for clinical research as a by-product. The proliferation of electronic medical records and personal health records can bring transformation in the conduct of clinical research -- new opportunities to find patients, integration of EMRs and electronic data capture (EDC), running virtual trials, identifying biomarkers, the list goes on.

Personalized Medicine
Obama demonstrated awareness of the potential for personalized medicine back in 2006 when he introduced the Genomics and Personalized Medicine Act. And while the act never became law, the passage of GINA earlier this year did bring some protection around the use of genetic information. Outgoing HHS secretary Michael Leavitt has left a note to Obama emphasizing personalized medicine as a potent tool for repairing the healthcare system, which should be a good reminder to the new president that there is still work left undone. Increased investment in personalized medicine will bring more companion diagnostics into clinical development with each new drug, affecting everything from sample size to study logistics.

Continuing Focus on Drug Safety
Most feel the pendulum has swung and the FDA is focusing on safety over accelerating drugs for efficacy. With the media focusing on everything from safety of drug imports (including ingredients used to manufacture drugs) to what seems like every anecdotal report, there is no sign of this trend changing. For clinical development, sponsors will continue to aspire to accelerated approvals -- but will plan for the realities of studies large enough to demonstrate safety (to prove that every needle has been found in the haystack).

Beyond Safety and Efficacy -- Comparative Effectiveness
Once upon a time it was sufficient to run a development program to demonstrate safety and efficacy. Lessons learned from the UK's National Institute for Health and Clinical Excellence (NICE) have taught us the future adds a third endpoint -- comparative effectiveness. In fact, recent healthcare plans in Washington suggest creating an independent "Comparative Effectiveness Institute" for the United States, tasked with head-to-head comparisons of quality and cost for one drug vs. another. Be sure to have a few more voices at the table when writing that next registration study protocol (outcomes research, evidence-based medicine, etc).

Autism and Vaccine Safety Research
Obama and McCain were both enjoying the response of crowds on the campaign trial when raising the potential link between autism and vaccines. Assuming this campaign themes travel from Chicago to Washington in January, there is certainly the suggestion of additional research for vaccines new and old.

Stem Cell Reversal
Most seem to be anticipating an Obama reversal of the Bush restrictions on stem cell research. If this happens and if this research is successful, it would still be several years before one would see any heightened impact of stem cells in clinical research. But clinical trials of stem cells would certainly bring heightened planning -- from dose setting to safety monitoring.

New FDA Leadership
Other far more qualified political sources have taken educated guesses at naming the next FDA commissioner (including Scientific American's proposal of Stephen Colbert). We will need to wait and see in a few weeks, but the new leadership will certainly be expected to bring change within the agency -- which in turn will bring it's impact on clinical research.

Doing More with Less (and less and less...)
We have heard it time and time again. Big pharma are being hit by loss of patent protection to generics coupled with a weak pipelines and the growing risk of reimportation. And now small biotechs are expected to see challenges in raising capital to maintain their development work due to the credit crisis. This conspires to mean a familiar message for clinical development -- the need to do more (more products, more trials) with less. Except the "more" seems to keep growing and the "less" keeps shrinking.

What will come to fruition? Time will tell. But at last check we still have an aging population
in this country, and plenty of unmet medical need to go around. (Personally, I am going to make sure I know what HIT, EMR, and PHR all stand for...)

Image: Flickr