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New tools take time
June 2011
by Peter T. Kissinger  |  Email the author

I'm feeling better. It may just be that many of us are tired of negativity. We are so fatigued from it that we are getting things back on a positive track. Our undergraduates have left town and the reduced traffic in West Lafayette calms the soul and our labs buzz with fresh new ideas. Life science venture funding is up a little bit. The federal budget has been kinder to science than it might have been. On both ends of the political spectrum, we agree that spending must come down and tax revenues (I didn't say rates) must go up.  
Happy days are here again. If not, it's up to us to make it so. I list here a few topics that I find interesting, where progress has been quite good against early negative thinking.
Adaptive clinical trials: This one has been under consideration for some time, but seems to be accelerating with better computational tools and the pressure to conserve time and money. Earlier, one wouldn't peek at the results from a classical double blind trial until it was over, or something went drastically wrong along the way. This is satisfying only in its simplicity. Suppose the wrong dose was chosen? Suppose the inclusion criteria for patients were too broad where some would benefit, some not respond and others would suffer? We'd like to know sooner. While this is a subject for experts, I'm encouraged to see this methodology being refined and gaining in popularity. provides transparency with clinical trials intentions and results. It's helpful to know what has not worked. Sharing the disappointing data is a very good thing. While this got started only recently (September 2007), progress has been very good. It's easy to search on your favorite disease and see those studies that have been completed and others in process. You can learn about the endpoints, inclusion/exclusion criteria and much more. Take a look.  
Molecular imaging of cells, organs, and mammals, based on a wide variety of principles, is making a dramatic difference in discovery, preclinical and clinical development. This has moved from the esoteric to the routine. It's a validated approach. There are some amazing new variations, such as cell imaging on the fly with flow cytometry and imaging of biopsied tissue with mass spectrometry. It's going to get a lot better and more economical. While we all looked at pond water creatures swimming about on a microscope slide in high school biology, for most of my scientific life, when cells were to be seen, they were also to be dead, fixed, stained and everything but stuffed. Now they can be seen very much alive with specific components labeled. The definition of a microscope has broadened to an amazing array of high-performance devices. FRET and FRAP may sound like cartoon characters of old, but they are making biology history today.  
Personalized medicine (at least patient segmentation into more narrowly defined classes) is gaining ground with diagnostics that are prognostic of both pharmacology and toxicology. While approved companion diagnostics remain few, markers during clinical research phases support the mechanism of action, while demonstrating efficacy and safety. Early success presages further change. Five years ago, there was much skepticism, but that is slowly abating. Related terms such as "targeted" or "tailored" therapeutics are frequent additions to the lexicon and likewise are real. Genomic characterization of cancer biopsies is now an available tool for personalized medicine. Given the long-understood phrase that children are not small adults, pediatrics remains a personalized medicine challenge that is getting attention, but continues to suffer from both financial and ethical realities. Being aware of a problem is the first step to solving it.
Dried blood/plasma spots on cellulose have been featured in a number of recent bioanalytical publications, taking the idea from its origins for qualitatively detecting inborn errors of metabolism to a new tactic for sample collection and transport for quantitative pharmacokinetics. This is made possible primarily by advances in mass spectrometry. It's too early to say for sure what the acceptance of the technology will be, but no doubt some great minds are in the lab sorting out the several challenges. Here we have another example of precompetitive technology where sharing among pharma and CROs is advancing the art. I am confident that this will not replace liquid samples to the extent the early proponents have predicted.  
Malaria, HIV and TB: Altruism is making progress here with open innovation among pharma, academic institutes and not-for-profit firms. For example, new approaches to an infectious disease are being explored after a nearly 50-year hiatus in the case of tuberculosis. It is very gratifying to see the altruism of pharma sharing libraries for this effort. More rapid diagnostics for TB are also becoming available, potentially saving many weeks of time. The Global Alliance for TB Drug Development now includes the Global Health R&D Center of China. Imagine trying that in 1970.  
Rare diseases: Some 6,000 to 8,000 diseases have been too rare to attract investment in pharmacology. Thus, another consortium is assembling this year with the unsurprising name of International Rare Disease Research Consortium. A number of national health organizations are signing on to participate, among them the European Commission and the U.S. National Institutes of Health (NIH). The challenges are daunting when it comes to return on R&D investment and achieving statistical power in clinical trials when the entire disease cohort can be in hundreds, not millions. It therefore makes sense to plan to use global resources wisely and to share thoughts and data for the common good. I suspect that the biology of these unusual cases may well help sharpen solutions for more common diseases as well. Diseases thought to be common (such as cancer and influenza) are becoming much more rare as subclassifications are revealed. Along the same lines, the NIH Chemical Genomics Center (NCGC) has created a database of approved and currently investigational drugs. This approaches 3,000 drugs approved in several countries. It promises to stimulate the repurposing of approved drugs for rare diseases, by providing sample compounds for screening.
Every biopharma, big and small, must balance the cost of too many projects versus the risk of too few. There is no way to get this right except by luck. Planning cannot work! This is the problem with science! If we knew what was going to happen, it would not be science, but rather engineering! Sharing risk and best practices sure beats the "not invented here" closed environment of the 1980s. All the examples noted above are enhanced by sharing data and open debate. It's been a rough first half in 2011, but beneath the noise, much progress is being made, and the last five years have been a lot more productive than we take time to realize. The glass is not empty.
Peter Kissinger is chairman emeritus of BASi, CEO of Prosolia in Indianapolis and a professor of chemistry at Purdue University.  



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