research and development – The Health Care Blog

Mission Critical: How Translation-Focused Disease Foundations May Save Medical Research

Apr 23, 2012• 1

By David Shaywitz, MD

Patients waiting expectantly for medical research to produce important new cures are finding bad news almost everywhere they turn.

Pharmaceutical companies are suffering from a much-discussed innovation crisis, as old drugs lose patent protection without new drugs to replace them; meanwhile, the small biotechs that could potentially bail big pharma out struggle to raise capital .

University scientists, for their part, are beset by an unseemly credibility crisis, as the intrinsic fragility of medical research is now vividly apparent from the soaring number of high-profile retractions, and the well-documented difficulty of reproducing many published findings outside the originator’s lab.

At the heart of this crisis is the misalignment of two very different cultures.

Academic scientists tend to focus on publishing papers, and usually assume that the results will eventually be useful. They place a high value on novelty, and relatively less value on whether the data are robust, easily reproducible by others, or truly relevant to human disease. Captivating data from putative laboratory models of disease generate publications, even if the model is not very predictive of human disease – and unfortunately, most models aren’t.

Conversely, big companies traditionally focus on generating efficiencies through scale, and on developing reproducible processes. This works very well for manufacturing, reasonably well for large late-stage clinical trials, and essentially not at all for early-stage (discovery) research.

Curing cancer: Too Important — and too Difficult — for University Researchers to Do Alone

Apr 1, 2012• 2

By David Shaywitz, MD

The central dogma of drug discovery is that academic basic research -> industry applied research -> new medical product. The disappointing number of impactful new medical products have been a source of endless soul searching, and could in theory be attributable to any (and all) of the steps in this model – and might also, as some have suggested, reflect the need for an entirely new conceptual framework.

The latest issue of Nature features a spot-on commentary (subscription only) by Glenn Begley and Lee Ellis (nicely summarized in this terrific Reuters article) that focuses in on the first arrow, the translation of academic oncology basic research into application by industry, and highlights the uncomfortable and inconvenient truth that by now isn’t a very well-kept secret: basic science is unbelievably fragile, and a lot of it doesn’t stand up to serious scrutiny.

This observation is absolutely consistent with my own experience and observations (see here, here, here, and here), as well as with those of Bruce Booth (this is a terrific discussion), and of course the pioneering research of Stanford Professor John Ioannidis, whose work I discussed six years ago (here), and who has been profiled extensively since (e.g. this piece from The Atlantic).

We could spend a lot of time discussing why science is fragile; Begley and Ellis, for example, emphasize the need for a cultural change in the way preclinical research is conducted, particularly in the field of cancer.

At the end of the day, I suspect that the problem involves some combination of the law of small numbers, the appeal of narrative, the structural advantages of reinforcing dogma, and the difficulties of publishing negative results that might challenge it, especially if the dogma was advanced by senior leaders in the field who tend to play critical roles in reviewing papers for high-profile journals and in selecting which new research gets funded. While the process may ultimately be self-correcting (and I certainly believe that science “works”), the cycle time for this can be a lifetime (literally – in some cases I’ve heard it said you need to wait for someone to pass away before contrary ideas can truly gain traction).

New Models for Market Access

Dec 27, 2011• 2

By Ulf Staginnus

I cannot resist writing one more time about the entire market access discussion currently ongoing everywhere, as I believe many of those numerous articles and reports are missing the point.

It is amusing, at least to me, to see the continued flood of articles, consultant presentations, blogs, congress announcements, workshops, summits, reorganizations, speeches, etc. all over the place, basically suggesting how the industry just needs to throw a few more people with fancy titles here and there, coupled with slight organizational changes, onto the problem and involve stakeholders and—guess what?!—actually talk to patients and perhaps even payers and all of a sudden, like Alice in Wonderland, everything will be good, after all.

The uncomfortable truth is, it won’t be. All this “noise” is only good for one thing, paying the bills of the consultants, which is fine, too, as I have been one myself so I can understand. But it will not address the problem the research-based pharmaceutical industry and its employees are facing. Without a substantial increase in R&D productivity, the pharmaceutical industry’s survival (let alone its continued growth prospects), at least in its current form, is in great jeopardy.