Two Books well worth the time

For any readers who expected a long essay on Chile, this is not it. Instead, as a sort of preamble to Chile, I want to tell you about the two books that served as much of my “airplane reading.”

I found both books, Genentech, The Beginings of Biotech by Sally Smith Hughes and Science Lessons, What the Business of Biotech Taught Me About Management by Gordon Binder and Philip Bashe, as part of my homework for my own non-fiction book on the rise and fall of Scios and Natrecor. They are both university press publications, from the University of Chicago Press and Harvard Business Press, respectively. That, of course, explains why they weren’t on the tables at the front of your local bookstore when you came in to browse.

Does anyone else still do that? My favorite Ann Arbor bookstore is  Nicola’s Books, and I drop in whenever I’m in the neighborhood. Anyway, back to the topic at hand.

The title pretty well explains the subject of Genentech. Hughes does not spare scientific detail, but she writes about it deftly, blending into the narrative. Readers with even the most basic understanding of genetics will hardly notice that they have gotten a short lesson on recombinant technology along with a great story. Some of you may know that Gordon Binder is a former CEO of Amgen; he focuses primarily on the financial growth of the company. Again, the story is so well told that it carries the weight of venture capital financing, cash burn, and initial public offering strategies without a whimper.

With both of these books, I found myself re-experiencing the excitement of my first undergraduate biology course. The Watson-Crick model of DNA was still new science. The whole world of biology had taken on new shape and meaning, and the individuals who started these companies blended science and business in a totally new way.

I loved David McCullough’s The Wright Brothers; these two books capture the same spirit of innovation in a discipline that has been part of our (at least, my) professional life.

Here’s another highly recommended example of outstanding non-fiction writing: Peter Moore’s  The Weather Experiment: The Pioneers Who Sought to See the Future.    

Why is this post on The Weekly Packet devoted to recommending three obscure non-fiction books? (The Wright Brothers is a best-seller; I’m not counting it.)  First, I can’t imagine writing about politics. Second, it’s still too cold to fish. Third, I wanted to slip in just a teeny plug for the nesiritide book because I just finished a second draft.

Stay tuned.

 

Standing at the bedside in Phase 1

Most of the folks who visit this site work in health care, either as medical professionals or in the pharmaceutical development industry. If you have not yet heard, last week a Phase 1 trial in France was complicated by five subjects experiencing very serious adverse events. One subject has died, and four others have had serious neurologic events, reportedly involving deep brain bleeds.

I had the opportunity to serve as a study responsible physician in a Phase 1 trial. The fundamental compound was a human hormone, and we had experience with it using intravenous administration. Nonetheless, we conducted a very careful Phase 1 trial with first-in-human precautions because we were administering it in a novel formulation linked to another molecule.

I went to our clinical pharmacology unit, at a center in Belgium, to be present for the first in human dosing. The setting was hardly dramatic, just a healthy young man lying on a Gurney with an IV, an automatic BP cuff, and ECG telemetry electrodes in place. An experienced study nurse gave the subcutaneous injection, and…nothing happened.

Of course, one of the six subjects in the first series would receive placebo, so on the following morning, we did it all again. Another subject, in the same setting, with another injection and … again, nothing happened. Since the arithmetic demanded that at least one of the two subjects was assigned active drug, one of the two subjects had received the very first dose of this compound ever injected into a human being.

What do you think when you are the “responsible” physician standing at the bedside for such an event? F. Scott Fitzgerald captured the experience perfectly. He wrote, “The test of a first-rate intelligence is the ability to hold two opposed ideas in mind at the same time and still retain the ability to function.” One idea is, “my goodness, we are making such a fuss over something that we know is safe.” The other, not surprisingly, is “I hope and pray that nothing goes wrong, but if it does, I hope I my emergency plan works and he will be all right.”

Our subjects were all right. But the subjects in the Bial trial were not. This is the enormous responsibility that everyone involved in research involving human subjects shoulders. Unexpectedly, despite our best efforts, something goes off the tracks.

Instinctively, we all feel sympathy for the subjects. Let’s also feel sympathy for the researchers who had high hopes for a safe and effective new drug, and were terribly, terribly wrong. We cannot brush bad outcomes under the rug. We need to talk about them, and to make sure that the lay public understands that pharmaceutical research is not a strictly commercial activity. It is a very human, and occasionally very dangerous, effort to make life better.

The drug price hullabaloo…

 

The Weekly Packet for Friday, December 11, 2015

This post comes a couple of days early. Dermatologic cancers are part of the price one eventually pays for a career in the cardiac catheterization laboratory, along with skiing, tennis, and fly-fishing. I have my third new lesion of the past 2 years, a real beauty (imagine growing a rhino horn just in front of your right ear). I’m having Mohs surgery on Friday. It’s all under local, and not a big deal, but can take quite a long time.

Campus issues at my alma mater, Amherst College in Amherst, MA, made the New York Times last week. My class of 1964, now 55 years post-graduation, has an active email list-serve (yes, kids, the old guys can adapt!) and the commentary has been spirited. Give me a bit more time on this one, though.

From time to time, “A-ha” moments come along where observations from several different settings suddenly click into place and make sense. Something along that line happened this morning while I was walking with Posie. For the past fortnight, the media have been filled with discussion about drug pricing and the rather significant bump in US healthcare costs this year. The “A-ha” went as follows.

In the disciplines of scientific and clinical research, we repeatedly tell ourselves that association is not causation. This is not true in journalism, where the process can easily be extended further to “juxtaposition implies association, and association implies causation.”

The journalists who do not do their homework would like to lead you along a path that is marked by logical, but false assumptions. A dramatic increase in the price for an off-patent drug for toxoplasmosis (Daraprim, Turing Pharmaceuticals) may be socially unjustifiable, but the incidence of toxo is not high enough for its treatment cost to impact the US healthcare budget. (See: http://www.nytimes.com/2015/09/21/business/a-huge-overnight-increase-in-a-drugs-price-raises-protests.html?_r=0 )

Here are a few facts to discuss with friends, family, and co-workers.  First, the three key drivers of US healthcare costs in decreasing order are: hospital care, physician and clinical services, and other professional services. Prescription drugs are very near the bottom of the list, just ahead of durable medical equipment. See: https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/downloads/highlights.pdf for the data.

What percentage of our health care spending goes for pharmaceuticals? The various figures range from a low of 9.7% to a high of 11.9%. The 11.9% figure comes from a reputable source, the OECD, so let’s use it, and round it off to 12%. If spending on pharmaceuticals increased a breath-taking 20%, the increase in total health care spending would be less than 2.5%. Actually, as a percentage of overall per-capital health spending, the US expenditures on pharmaceuticals are rather middle of the road. See: https://data.oecd.org/healthres/pharmaceutical-spending.htm#indicator-chart

This may be because “generics now account for 28 percent of pharmaceutical spending and 84 percent of drugs dispensed in the U.S., which is high by OECD standards.” http://www.pbs.org/newshour/updates/americans-spend-much-pharmaceuticals/. Absent the introduction of the very costly anti-hepatitis C drugs, the bill for branded drugs would probably have grown very little.

Now, to wrap up, let’s ask why the industry is getting such bad press when most of the facts don’t support it? Here, I am going to venture into opinion. I think the time has come to have some serious discussions with senior management about marketing. Here’s a direct quote from Ron Shinkman, http://www.fiercehealthfinance.com/story/big-pharmas-greed-continues-drive-healthcare-spending-and-prices/2015-02-16  “But the marketing of those [prescription] drugs has become at times questionable. John Oliver’s take on his HBO show last week was spot-on, poking fun at the young, sexy (and undereducated) pharma sales reps, the free meals and “thought-leader” designations for doctors, and the anthropomorphized bladders and other visual insanity in television commercials (Oliver was also kind enough to cite our sister site, FiercePharma). As a matter of fact, drug companies now spend more on marketing than product development. He didn’t even get into some of their even more troubling practices, such as lobbying Congress to bar Medicare from negotiating on pharmaceutical prices in bulk or buying them overseas, where the predominance of single-payer healthcare systems has forced drug companies to price their products at much lower prices.”

My take? When the ethical pharmaceutical companies ventured into “direct-to-consumer” marketing, they gave up far more than they gained. The widespread public respect for science-based companies that developed new medicines to manage or cure serious diseases was bound to crumble with “ask your doctor about (insert out drug)” followed by a list of contra-indications and adverse effects in the verbal equivalent of small print.

If those of us who work (or worked) on the scientific side of the pharmaceutical industry want to feel proud of what we do (or did), we have to realize that the industry itself has made some decisions that have not worked out well.