Bayh-Dole and the Academia-Industrial Complex

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This post was written by Maggie Mahar and Niko Karvounis

In 1980 Ronald Reagan claimed the presidency and America headed in a new, sharply more conservative direction.  It is no accident that this also was the year that “the corporatization of health care” in America began in earnest. This was the phrase that Paul Starr would use in his Pulitzer-prize-winning The Social Transformation of American Medicine to describe a revolution that would turn U.S. healthcare into an enormous for-profit business.

Thanks to changes in tax laws, for-profit HMOs would begin to replace not-for-profit  HMOs, and for-profit hospitals would begin to flourish. By 1986 for-profits had captured 14 percent of the nation’s acute-care hospital market. In this brave new world, more and more hospitals would be run, not physicians but by businessmen. After all, as Fortune magazine had declared some years earlier: “the management of medical care was too important to be left to doctors.”  Some physicians began to see themselves as entrepreneurs.  “Those who talked about ‘health care planning” in the 1970s now talk about “health care marketing,” Starr wrote in 1982. “Instead of public planning, there will be corporate planning.” And the goal driving that planning, Starr suggested, would no longer be better health, but rather “the rate of return on investments.”

Against that backdrop, in 1980 the Bayh-Dole Act was passed, and the face of medical research in America was forever altered.  The bill would bring academic institutions into the commercial world in a way that, at the time, seemed to ensure medical progress. Nature magazine offers a concise overview of the legislation, explaining that it “shifted the incentive structure that governed research and [the] development  . . . of federally funded [medical] inventions by allowing institutions to own inventions resulting from federally sponsored research and to exclusively license those inventions.” In other words, after Bayh-Dole, a university research team that came up with a drug could patent it and sell it to businesses.

This may seem hard to imagine today, but before Bayh-Dole, there was no such collaboration between those who invented a drug and for-profit companies.  Federally-funded research was considered a public good, owned by everybody and nobody. If, say, Doctor A created a breakthrough cancer drug at Harvard,  Doctor B at Stanford had free reign to experiment  with it as needed to improve it—as did other academics. There were no significant legal hurdles to open, ongoing collaboration and little profit attached to research.

Bayh-Dole changed all this, by granting academic researchers who
created new medications proprietary rights to their breakthroughs.  At
the time,  the idea was that granting intellectual property rights to
universities would promote innovation (1) by protecting inventors, thus
giving them the security of knowing that if they spent time and money
on a project, they would reap the financial rewards (2) spurring
competition by opening the possibility of making a profit on your
invention; and (3) marrying academia and industry so that industry’s
infrastructure could be used to more efficiently distribute new drugs
to patients and providers. 

What the legislators did not entirely understand is that the best
research scientists in academia work as hard as they can whether or not
there is hope of personal profit. They compete, not for money, but for
fame within their field —and the enormous personal satisfaction of
knowing that you have made a lasting contribution to medicine. Dangling
$100,000 in front of them may well get their attention, but it won’t
make them more creative or more industrious—though it may make them set
their own best ideas aside to do whatever the person with the $100,000
wants them to do.   

Nevertheless, at the time, “technology transfer,” i.e. exploiting the
practical and commercial applications of scientific research in the
commercial world, made sense: structure incentives so that we see more
inventions move from research to practical applications for patients. 

But Bayh-Dole has had many unforeseen consequences that, today, raise
some serious concerns about the future of medical innovation in the
U.S.

For one, the pipeline from academia to industry has turned out to be a
two-way street. Corporations aren’t just buying inventions once they’re
created; they’re actually ordering up innovations before they’re
developed by influencing research agendas. Business is telling academia
what it wants scientists to work on: products that can be easily
invented and easily sold, in volume.

Consider the case of Shiseido, a Japanese cosmetic firm, and Harvard’s
Massachusetts General Hospital. Since 1989, Shiseido has given Mass
General almost $200 million in order to secure first rights to
discoveries by hospital dermatologists. The Shiseido/Harvard deal also
included the formation of a joint company, the Cutaneous Biology
Research Center, dedicated to dermatological research.

One cannot help but pause to wonder if Harvard, with all of its wealth
(both in terms of dollars, and in human capital), might not fund
biological research that is pointed  in a more useful direction. These
days dermatology is without doubt, a profit center: baby-boomers want
to look younger and better. But they face problems more serious than
“barnacles of age”: Alzheimers, for instance, or acute macular
degeneration, which is expected to become the leading cause of
blindness among boomers.   

Nevertheless, Harvard took the $200 million and now must focus a
considerable share of its energy and resources on dermatology. Without
a shred of irony Shiseido’s website proudly touts the Biology Research Center as “an industrial-academic complex.”

This phrase, “industrial-academic complex"—or, as most people put it,
the academia-industrial complex—is the perfect encapsulation of
university and business links in a post-Bayh-Dole world. In the example
above, it’s not a question of transferring technology, it’s a question
of institutional collusion. In fact, it’s not just technology that’s
being transferred to drug companies—it’s the entire research process,
including the power to decide where to focus resources.

The Shiseido/Harvard example is by no means a rare case. Many of the
nation’s top universities have close partnerships with drug companies.
In 1998, pharmaceutical giant Novartis cut an unprecedented—and much
criticized—deal with the University of California at Berkley. The
company committed $25 million over five years to Berkley’s Department
of Plant and Microbial Biology to support research in agricultural
genomics. In return, states a ’98 Berkley press release,
“Novartis scientists will work closely with UC Berkeley researchers,
and the company will receive first rights to negotiate for [rights to]
roughly 30-40 percent of the discoveries made in the department.” This
proportion corresponds to the share of “the department’s total research
budget provided by Novartis, and will vary from year to year.”

Yes, you read that correctly. At one point, a multinational drug company underwrote forty percent of the budget for an entire university department at a top-flight institution.
What happens to academic freedom when a department is so indebted to
one company? What happens to a research scientist in that department
who has made what looks like a breakthrough that is heading in a
different, long-term direction? 

Novartis, like other major pharmaceutical companies, is more interested
in short-term gains than long-term risks. Its shareholders want to see
earnings growth—year after year. Does this mean that the next Jonas
Salk will be told that he should get with the Novartis program—or
forget about tenure?

Here again it’s clear that drug companies aren’t just waiting for
breakthroughs to emerge. Rather, they’re trying to co-opt research
agendas to direct them toward fields in which they have a commercial
interest. (Novartis has an agribusiness wing called the Novartis
Discovery Institute).

Sometimes the industry bias in guiding research agendas is simply
stunning. In October 2007, Novartis struck again, this time brokering a
$65 million dollar grant
to MIT. The grant funds a partnership with the company to research new
techniques for making drug manufacturing quicker and cheaper. It goes
without saying that a more efficient, cost-effective drug manufacturing
process would be a boon, first and foremost, for drug companies. And in
true Bayh-Dole fashion, MIT and Novartis will jointly share the rights
to any research they develop together –and both can generate revenue by
licensing technology to other companies.

One important component of the Novartis/MIT deal is that academic and
corporate researchers will regularly work side-by-side on common
projects. This sort of cross-sector, on-the-ground collaboration is an
increasingly important component of the academia-industrial complex.
Earlier this year, Washington University in St. Louis announced a $25
million partnership with Pfizer to study immuno-inflammatory disorders
such as arthritis and asthma. A university press release
notes that this coupling is noteworthy because “[in] previous paradigms
[of academia-industry collaboration] pharmaceutical companies have
provided funding to academic institutions for research projects
primarily conceived and conducted by university researchers. [But this]
new model stresses equality in intellectual input, commitment and
execution by both parties…” Now not only are drug companies funding
self-serving research agendas and pre-paying for licensing rights;
they’re also staffing the research teams. They are taking over medical
research.

Such an intimate union between universities and drug companies raises
concerns. The most obvious problem is basic conflict of interest: when
a university gets millions of dollars from a drug company, it becomes
obligated to its benefactor.  As Marcia Angell, a senior lecturer at
Harvard Medical School, put it in a 2000 NEJM editorial,
“close and remunerative collaboration with a company naturally creates
goodwill on the part of researchers and the hope that the largesse will
continue. This attitude can subtly influence scientific judgment in
ways that may be difficult to discern.” Research
has shown “that researchers with ties to drug companies are indeed more
likely to report results that are favorable to the products of those
companies than researchers without such ties.”

Unfortunately, today drug industry ties are endemic in medical
academia, and not just at the institutional level. An October 2007 JAMA
survey
found that out of 459 department chairs at medical schools, 60 percent
had some form of personal relationship with industry. These
relationships included serving as a consultant (27%), as a member of a
scientific advisory board (27%), as a paid speaker (14%), as an officer
(7%), as a founder (9%), or as  member of the board of directors (11%).
The same survey found that two-thirds of medical school departments had
relationships with industry.

And just as drug companies are intervening in the research process
earlier and earlier, they’re also reaching medical researchers in their
formative years. A 2005 JAMA study
found that the average exposure of a given third-year medical student
to the drug industry was one gift or sponsored activity per week. Of
826 surveyed medical students, 93.2 percent were asked or required by a
physician to attend at least one sponsored lunch over the course of the
school year.

This is all troubling and it raises an important question. When
universities are married to industry from the level of individual med
students all the way up to the institution’s top scientists, who is
left to engage in medical research that’s not tied to industry?

Think about it: if the medical research agenda is solely contoured to
commercial interests, then we miss out on a lot of high-quality
science. In 2001, Eric G. Campbell, a researcher at Massachusetts
General Hospital’s Institute for Health Policy, told The Boston Globe
that “basic science [directed by curiosity and creativity, rather than
practicality] is what fuels the next generation of clinical
discoveries. And if we start focusing just on research that has an
immediate commercial application, at some point in the future we’re
going to get a slowdown in clinical discoveries.” When everyone is
focused on synthesizing acne pills and streamlining drug manufacturing,
no one is  left to patiently ponder our most difficult medical
problems.

This isn’t just an abstract worry—data supports the notion that the
commercialization of medical research has gone hand in hand with a
slow-down in meaningful innovation. A 2006 GAO study found
that the pharmaceutical industry increased its R & D budget, which
often includes academic partnerships, from $16 billion in 1993 to $40
billion  in 2004 (after inflation). This was a 147 percent increase.
Yet over this same period, the number of drugs classified as variations
of existing medications (a.k.a. “me too drugs) submitted to the FDA
increased at a rate of 38 percent.  Meanwhile, the number of brand-new
drugs submitted to the FDA increased by just 7 percent over the eleven
years in question. 

This is hardly commensurate with the industry’s 147 percent boost in R
& D funding.  It seems that industry was using the bulk of  its
R&D money to develop variations on products that we already
have—i.e. yet another allergy medication. (Companies also frequently
label some of the money that they spent courting  and “educating”
doctors as “R&D.”)

More profit and less innovation; this is hardly what Bayh-Dole
promised. But this perverse dynamic is actually built into a system of
research centered on owning intellectual property and turning a profit
on it. GAO reports that “companies can easily obtain new patents by
making minor changes to existing products regardless of whether the
drugs offer significant therapeutic advances.” This creates the
incentive is to do just enough to make something patentable—without
having to risk the manpower and money needed to create a real
breakthrough.   Thus we get “line extension” as “new products [are
derived from] existing compounds by making small changes to existing
products…”

Bayh-Dole was not Washington’s only gift to the pharmaceutical
industry. In 1984, Congress passed the Hatch-Waxman Act which allowed
“pharmaceutical companies to develop new uses for previously approved
drugs that have no patent protection and receive an additional three
years of ‘market exclusivity.”’ At this point, companies became so
protected against risk that they had no reason to take a risk:  all
they had to do was to  come up with a new application for an existing
drug and they could extend their monopoly. Yet true innovation is all
about risk-taking.

Thus “technology transfer” pulls universities into a loop of mediocrity
because it encourages them to perform research on drug company terms,
and focus on short-term applications that are, above all else,
commercially viable.  To be sure, universities aren’t victims here:
every year they pull in $2 billion for academic research centers
through patent licensing agreements. In fact, universities like Harvard
and MIT actually lobbied Congress in support of Bayh-Dole way back
when. Nor are schools doing all they can to protect research integrity:
only about one-third of universities have institutional conflict of interest policies regarding their research investments.

In a post-Bayh-Dole world, knowledge is patented, monopolized, and
commoditized. As a result collaboration between Professor or A at
Harvard  and  Professor B  at Stanford becomes much, much less
likely—but collaboration between Professor A and Big Pharma becomes
almost a sure thing. And the big drug companies don’t share
research—they compete, spending millions while working on parallel
proprietary projects.

In Money-Driven Medicine, Genie Kleinerman, chief of pediatrics
at Houston’s M.D. Anderson  Cancer Center, recalls a time when she was
doing work on two drugs made by different companies. “Together, they
seemed to do a better job of targeting malignant cells of osteosarcoma,
a bone cancer that occurs in children. In the lab, we had shown that
you could combine the two agents. Scientifically, it was fine but now
we needed the companies to do clinical trials. My lab work was being
provided free, but in order to get approval from the FDA, they needed
to invest in trials and collect the data.

“But we just couldn’t get them to do it,” she recalls, reliving the
frustration. “The lawyers for the two companies couldn’t come up with
on an agreement on who would own the rights to the combination and who
would pay for what.” That was a number of years ago. “Today it would be
the same situation—or probably worse. The pharmaceutical industry has
become so protective of who owns the intellectual property you probably
couldn’t even get them to sit down at the same table.”

If this trend continues, expect to see fewer independent researchers
and a growing neglect of long-term, visionary medicine in favor of
immediate commercial opportunities.

Yet there are signs that  individuals within America’s ivory towers are
deciding to put some distance between themselves and industry: Just
last month, the New York Times reported
that “a number of prominent academic scientists have made a decision
that was until recently all but unheard of. They decided to stop
accepting payments from food, drug and medical device companies. No
longer will they be paid for speaking at meetings or for sitting on
advisory boards. They may still work with companies. It is important,
they say, for knowledgeable scientists to help companies draw up and
interpret studies. But the work will be pro bono.”

This, of course, is not the same as institutions establishing an
arms-length relationship with industry. But it does show a growing
concern about entanglements with for-profit-companies that could
compromise scientists—and science.

The times are changing. It’s no longer 1980.

20 thoughts on “Bayh-Dole and the Academia-Industrial Complex”

  2. The Bayh-Dole Act, by turning over research from the government to big pharma, and the shifting from the institution-based, inpatient setting to community-based, ambulatory sites for treating the majority of the nation’s cancer patients, has turned cancer treatment back a whole generation.
    There was a major downside from a scientific standpoint. Scientists were limited in how they could discuss things with their colleagues until intellectual property was protected by a patent. They were concerned about publishing articles and presenting in public. It was a major obstacle in terms of the way scientists operated. Scientists did the science and the business types translated their findings.
    And by giving individual institutions the ownership rights to intellectual property and new technologies developed on campus, profits had to be protected. Clinical trials had private industry enter into the equation. For-profit companies take over the venture, doling out payments along the way, paying the university royalties. The business side of academia had exemplified the commercialization of publicly-funded research.
    We have produced an entire generation of investigators in clinical oncology who believe that the only valid form of clinical research is to perfrom well-designed, prospective randomized trials in which patients are randomized to receive one empiric drug combination versus another empiric drug combination.
    Prospective, randomized, controlled clinical trials cost millions of dollars, but the most promising non-conventional drugs may be public domain, non-proprietary technologies, and therefore unpatentable. No company will invest that much money for something that is difficult to patent. This prevents serendipitous and fortuitous discovery.

  3. Congrats Maggie & Niko!
    Dr. Incognito chose this post for his weekly RedScrubs winner on redscrubs.com’s weekly wrap-up. Each week’s winner receives a free set of red scrubs (no catch). Email me if you want them so I can send the info.
    Sincerely,
    Dr. Incognito

  4. This is indeed a great American tragedy which as you say shows some signs of turning around.But sadly many individual and institutional reputations may never recover.
    Thank you so much-Maggie and Niko- for deconstucting it and presenting it so well.
    Dr. Rick Lippin
    Southampton,PA
    http://medicalcrises.blogspot.com

  5. My professional field was physics, but there has been a similar dynamic. It’s not the for-profits who are collaborating with universities (although that has happened too), but that federal funding is used to force research into avenues favored by the government. In practice this has meant areas of (potential) use to the military.
    No funding, no research. No research, no money for graduate students. No graduate students and the professor doesn’t get tenure. The schools also benefit monetarily since they keep 25-40% of the grant for “overhead”.
    Basic research has also vanished from the industrial sector. The big private labs (Bell Labs, Sarnoff, IBM, etc.) have either been gutted or shifted into applied work and product development. The blue laser (used in the new DVD players) was invented in Japan.
    I keep saying that one of these days a “cure” for cancer will be discovered in, say, China and they will figure out that this gives them an economic advantage (lower health costs) and refuse to share it. The US already does this, in effect, when local firms price their offering out of the reach of poor countries. The biggest scandal was over the HIV drugs, but there are others.
    Perhaps the next “war” will be over intellectual property and not oil.

  6. To complete the picture it would be useful to see the level of funding for university and other non-profit institutions by government agencies over time.
    I’m guessing that this has declined in inflation adjusted terms and that many labs have been forced to go to drug companies for funding to make up for the lack. I also think that the results of the Bayh-Dole bill were not as unanticipated as might be believed. I think it was yet another part of the privatization of everything that has been the theme in the US for the past 40 years.

  7. Several thoughts on this.
    First, the percentage of hospital beds controlled by for profit hospitals has been stuck at about 15 percent for the last two decades at least. Yet, hospital costs (both inpatient and outpatient) are the fastest rising segment within healthcare even though 85% of the beds are owned and controlled by non-profit institutions and even though the number of beds has been declining for 25 years or more.
    Second, the NIH is free to do all the basic, blue sky research that it can get funding for. If it makes some worthwhile discoveries, it can license them to the drug companies too and capture that revenue for itself (and taxpayers) to fund further research. Besides, drugs only account for about 13%-14% of healthcare costs, and 65% of all prescriptions are now generics, though they account for only about 16% of the dollars spent on drugs according to IMS Health.
    Third, I think there is a simple intermediate to longer term solution to the drug industry’s focus on developing “me too” drugs. If comparative effectiveness research shows that they are not as cost-effective as older drugs already on the market (including generics), don’t cover them! Last year, UnitedHealth Group, for example, stopped paying for Nexium because it was deemed no more effective than the older and much cheaper Prilosec and its generic equivalent. Savings to employer clients: $150 million per year.

  9. Barry, Robert, Dr. Rick,
    Thanks for your comments.
    Barry I ageee that refusing to cover “me too” drugs would have a chilling effect on their production. But Medicare will do that only if there is a major change in attitude at CMS. Right now, CMS is loathe to do anything that would upset the drug industry . . .but that could change, expecially as it becomes apparent that Medicare is running out of money.
    My only question would be: “was Nexium good for some patinets who for some reason couldn’t tolerate the less expensive drug?”
    Often some of these drugs are useful for a small group of people, and sometimes when insurance companies decide not to cover something they don’t take this into account. That’s why I’d rather see these decisions made by independent boards of physicians who have no financial interest one way or the other and can approve coverage for the small group that needs it.
    You’re right that the for-profit hospital share has remained stuck at 15 percent. They’ve run into a lot of problems in terms of corruption: lying to Medicare, lying to private insurers, lying to shareholders, lying to patients, FBI raids and federal indictments.
    As I say in the book, I think it’s very v,ery hard to make a profit in the hospital business–just as in the airline business. (Though there seems to be much less corruption in the airline business–they just go broke.)
    The hospital business is unpredictable and its labor intensive. Moreover, if you try to downsize, patients die.
    Spending on hospitals in general has gone up steeply in large part because the cost of hospital equipment, medical devices and the drugs you receive in hospitals have risen sharply. Those costs are all in your hospital bill, and some of the most expensive drugs (chemo for cancer in particular) are usually administered in hospitals rather than bought retail.
    I’d estimate drugs and devices now equal about 15% to 16% of health care spending: 11% –the drugs you and I buy retail at a pharmacy–another 2% or so–the drugs administered in a hospital or doctors’ office, and another 2% to 3%– the cost of devices.
    The device sector is growing more rapidly than the drug sector as the number and types of devices proliferate: stents, artifical joints, defribillators etc. etc..
    Finallly, nurses’ salaries have gone up significantly. They really needed to be raised; nursing had become an underpaid “women’s professoin.”
    But even with the raises, there is a shortage of nurses. The work is too hard and the pressure too intense for the salaries that many hospitals pay. . . Many nurses would rather work in a less chaotic setting.
    Finally, you write: “Second, the NIH is free to do all the basic, blue sky research that it can get funding for. If it makes some worthwhile discoveries, it can license them to the drug companies too and capture that revenue for itself (and taxpayers) to fund further research.”
    This is the way it should work but unforunately NIH licenses its research to drug-makers at much less than market value. (The Congressmen who write the laws that govern NIH take hefty contributions from drug-makers.) Then the drug-maker overcharges for the drug–and government (taxpayers) wind up paying for it.
    AZT, the first drug that really worked to treat AIDs, is a famous example, It was developed by govt’ scientists, then industry licensed it, and sold it for over $6,000. Often, Medicaid wound up paying the $6,000. .
    Moreover, and this is incredible–NIH refuses to disclose how much it receives in these licensing agreements–presumably because it doesn’t want to disclose that taxpayers are being cheated. Here’s the background to the case:
    ” In July 2000, Public Citizen Health Research Group filed a Freedom of Information Act (FOIA) lawsuit against the NIH seeking royalty figures (including percentage of sale royalties) identifiable by company for each license the NIH Office of Technology Transfer executed from 1986-1998. Historically, NIH has taken the position that such information is protected from release under the confidential commercial/financial provisions of Exemption 4 of the FOIA.Opinion: On March 12, 2002, Judge Colleen Kollar-Kotelly, United States District Court Judge, granted NIH’s Motion for Summary Judgment and denied Public Citizen’s Motion for Summary Judgment. The Court concluded that the NIH appropriately withheld the royalty information pursuant to Exemptions 3 and 4 of the FOIA.”
    Robert– I don’t think either Bayh or Dole intended all of the consequences of Bayh-Dole; they weren’t as far to the right on these matters as some in the Reagan administration. But you’re right, Bayh-Dole was part of the overall push by the Reagan administration to privatize everything (just as Thatcher was doing in the U.K.)
    I do remember when Bell Labs was a hotbed of creativity. . . It’s interesting to hear how much the military now controls or directs research. This is the “military-industrial complex” that Eisenhower tried to warn us about . .
    I wouldn’t be surprised if the cure for cancer finally comes out of someplace like China, (or India.) As Gregory said earlier in this thread, the fact that. cancer reserachers don’t share information with each other, but work in their own silos has greatly slowed progress.
    The next war could be over intellectual property–or water.
    Dr. Rick–thank you.
    Gregory–I’m afraid we have become that callous.
    But perhaps we’ve reached such an extreme that we’re ready for a pendulum swing. One can only hope so.

  10. Maggie, your comment about “only if there is a major change in attitude at CMS…CMS is loathe to do anything that would upset the drug industry” sends chills down my spine. I know you are working on a posting about the nursing home industry, so I’ll wait until then to comment much further.
    But the “CMS loathing to do anything” has hit home this week, in regards to the latest Pennsylvania Department of Health inspection by surveyors at a Manor Care nursing home in Sinking Springs, Pennsylvania.
    CMS contracts out the oversight of each nursing home to each state’s health department. Numerous reports have shown how corrupt the oversight system is, especially during this Administration.
    Stealth moves – like putting out the word that surveyors shouldn’t cite anything they don’t absolutely have to, cutting or under-funding oversight budgets, look at self-reported not non-audited data, etc. With The Carlye Group take-over of Manor Care, this just got worse. Look forward to your future report on nursing homes.

  11. Gregory–
    Thank you for the information. And I am
    going to be writing about the nursing home industry soon.
    Unfortunately, it’s a rich topic.

  12. Gregory–
    Thank you for the information. And I am
    going to be writing about the nursing home industry soon.
    Unfortunately, it’s a rich topic.

  13. Unfortunately, it was not a rich topic in Congress. The House Energy and Commerce Subcommittee on Oversight and Investigations has not held an oversight hearing about nursing home care since 1977.
    Chairman Bart Stupak, finally held an oversight hearing this week on nursing home care. It’s supposed to be the first in a series of hearings the subcommitte plans to hold on long-term care financing and quality-of-care issues.
    Why do I think “the check is in the mail” about this?

  17. Recently published on http://www.brainblogger.com
    The Human Injury of Lost Objectivity
    If I were to rate the corruptive tactics performed by big pharmaceutical companies, the intentional corruption of implementing fabricated and unreliable results of clinical trials by pharmaceutical companies by hired third parties who manipulate these trials they sponsor because of their power to control others involved in such trials that is largely absent of regulation would be at the top of the list, and likely the most damaging to the requirement of authenticity and, more importantly, assuring the safety of the public health, as I understand that this does in fact occur.
    Decades ago, clinical trials were conducted at academic settings that focused on the acquisition of knowledge and the completely objective discoveries of meds. Then, in 1980, the Bayh-Dole Act was created, which allowed for such places to profit off of their discoveries that were performed for pharmaceutical companies in the past. This resulted in the creation of for-profit research trial sites, called Contract Research Organizations, which is often composed of community research sites with questionable investigators possibly void of necessary research experience or quality regarding their research purpose and ability. Since they are for- profit, with some CROs making billions of dollars a year. The trials conducted at such places are sponsored by pharmaceutical companies that control and manipulate all aspects of the trial being conducted involving their med being studied in the trial. This coercion is done by various methods of deception in subtle and tacit methods. As a result, research in this manner has been transformed into a method of marketing, which includes altered results of the trial to favor the sponsor’s med. Their activities are absent of true or applied regulation, and therefore have the autonomy to create whatever they want to benefit what may be a collusive relationship between the site and the sponsor.
    Further disturbing is that once the creation of the trials is completed, they are then written by ghostwriters often, although no one seems to know how often. These people are not identified and acknowledged by the sponsor, and may not be trained in clinical research overall, as they are simply freelance writers, as one does not need research training or certification in order to perform this function. Rarely do trial ghostwriters question their instructions about their assignment, which is clearly deceptive and undocumented by the sponsor. Also, these hired mystery writers are known to make about 100 grand a year. This activity removes accountability and authenticity of the possibly fabricated clinical trial even further. The corruptive act is finally completed by the sponsor hiring an author to be placed on the trial that likely had no involvement with the trial, and, along with others, was paid by the sponsor for doing this deceptive act.
    To have the trial published, the sponsor pays a journal to do this in various ways, I understand, such as purchasing thousands of reprints of their study from the journal. Again, how often this process is performed is unknown, yet frequent enough to create hundreds of such false writers and research sites to support the pharmaceutical industry. So benefits of meds studied in such a malicious way potentially can harm patients and their treatment options and safety risks. The purchased reprints are distributed to the sponsor’s sales force to share the content with prescribers which may lack validity.
    Such misconduct discussed so far impedes research and the scientific method with frightening ethical and harmful concerns, if in fact true based on reports by others. If so, our health care treatment with meds is now undetermined in large part with such corruptive situations, as well as the possible absence of objectivity that has been intentionally eliminated. Trust in the scientific method in this type of activity illustrated in this article is absent. More now than ever, meds are removed from the market are given black box warnings. Now I understand why this may be occurring.
    Transparency and disclosure needs to happen with the pharmaceutical industry for reasons such as this as well as many others, in order to correct what we have historically relied upon for conclusive proof, which is the scientific method. More importantly, research should not be conducted in a way that the sponsor can interfere in such ways described in this article, requiring independent sites with no involvement with the drug maker. And clearly, regulation has to be enforced not selectively, but in a complete fashion regarding such matters. Public awareness would be a catalyst for this to occur, after initially experiencing a state of total disbelief that such operations actually are conducted by such people, of course. We can no longer be dependent on others for our optimal health. Knowledge is power, and is also possibly a lifesaver.
    “Ethics and Science need to shake hands.” ……. Richard Cabot
    Dan Abshear

  19. The Price of Innovation and the Progression of Illness: Biopharmaceuticals
    Recently, you may have heard or read in mass media sources about the issue of what are known as pharmacy benefit managers that have clients who are prescribed medications created by what are known as red biopharmaceutical companies. Being truly innovative therapies for patients, they are very costly and require those who are prescribed such drugs to pay a great deal of money due to the placement of these meds on their PBMs on the highest level, which is a 4 on a tier 4 system.
    PBM is an acronym for a pharmacy benefit manager and is insurance for prescription medications, along with perhaps being owned by your health insurance company. The co-pay that is asked of you is at the discretion of both the PBM and your employer who may provide the PBM to you, without you being involved in such a dialogue. Kickbacks and collusion are possible between employers and PBMs, so how medications are tiered on a PBM may have nothing to do with what is best for you, as variables that are considered in such a negotiation are known only by the PBM employee and your employer.
    Regardless, biopharmaceuticals presently require co-pays that at times may be 1000 percent or more than medications on other levels of the 4 level systems. And many believe the surreal price tag placed on these biologic treatments is no justified.
    Beginning in the 1970s, followed by the implementation of the Bayh-Dole Act in 1980, biopharmaceuticals were being created at a notable rate for new treatment for those who typically have a serious medical disorder by academic researchers often paired with venture capitalists. They were a new paradigm of medical treatment, as biopharmaceuticals make and modify large molecules, such as a hormone or a protein, by utilizing a living biological system. The medications that existed before this advent were synthetic, small molecule and carbon based medications. Some say the cost to make a biopharmaceutical is only a third more expensive than the older generation drugs Yet the price of biopharmaceuticals can be 10 times or greater than other medications, and perhaps the cost was determined for what previous treatments cost, such as chemotherapy, which I understand can cost quite a bit as well.
    Synthetic insulin is an example of such a biopharmaceutical treatment option for the patients with diabetes who need insulin replacement. Furthermore and presently, generic biopharmaceuticals are not allowed, which will be called biosimiliars. And with biopharmaceuticals, there are about ten types of large molecular therapies for various disease states. Yet out of close to 200 biopharmaceutical companies, only a small fraction of them are remotely profitable.
    Biotechnological medications began to be used primarily in the 1980s and now presently make over 60 billion a year, with about 20 percent growth in this market annually. This creation of innovation occurred soon after the activation of the Bayh/Dole act of 1980, which basically created capitalists out of academics using your tax dollars. This may explain the rapid growth of this new technology.
    With anemia patients, oncology and dialysis clinics are targets for two biopharmaceuticals that are identical, yet owned and named differently, which are Procrit by Johnson and Johnson, as well as Epogen, made by Amgen. These biopharmaceuticals treat anemia is associated with the treatment and conditions for certain deadly and chronic diseases, such as cancer and kidney failure patients. Because of giving the doctors of these patients monetary rebates for the more they used of these two drugs.
    Because doctors chose to perhaps overdose very sick patients, these patients were harmed, as it kills them quicker if such biopharmaceuticals are not given at a low dose. Amgen produces the most popular therapies regarding this, and is the largest company as a result.
    Soon, nanotechnology will be the next innovation in creating similar medications. Yet for now, biopharmaceuticals will arrive with great anticipation of many to treat various forms of cancer soon, as this disease is the focus of biopharmaceutical development at this time.
    In fact, I have heard that about 30 percent of pending therapies are biopharmaceuticals that now have captured 10 percent of the pharmaceutical market. Arthritis therapies are anticipated as well.
    Another successful type of this type of therapy is a biopharmaceutical called Enbrel for RA, which is a devastating type of arthritis. The treatment was so popular due to the relief it provided for such patients, at one time, at least 1,000 patients each week had to wait for the drug to arrive, as it could not be created fast enough. Launched by Immunex in 1998, RA patients clearly benefited and were relieved by this treatment that now exists for them. Anticipating the need and success of Enbrel, a large pharmaceutical company which is now Wyeth bought Immunex soon before or after Enbrel was launched, yet acquired most of the stock of Immunex before its approval. Today, Enbrel is promoted by both Amgen and Wyeth and is the top selling biologic available.
    Another biopharmaceutical company that got noticed was Genzyme, and they made anti-viral meds that were biotech products, and marketed them after acquiring the presumed business acumen of Don Rumsfeld in 1977, who shared in the profits because of this mutual relationship of the two. Genzyme produces biopharmaceutical for rare, but deadly diseases, and are known to charge the most for their products.
    Furthermore, Mr. Rumsfeld was CEO and president of a pharmaceutical company called G.D. Searle in 1997, which is now part of Pfizer.
    Yet, some claim that the benefit value provided to these sick patients is a bit limited, considering the high cost of biopharmaceuticals. Very few extend life of these sick patients much.
    However, at this time they may be limited to their treatment options. Is it really worth tens of thousands of dollars a year for the very sick to have their lives extended minimally for the most part?
    Presently, there are many that approach the FDA and aggressively insist that generic biologics therapies be allowed into the market for the benefit of these critically ill patients, and this would be of great benefit for such patients, and this can be done, as far as the generic creation of these meds that presently, and unlike traditional drugs, now have unlimited patents. And this situation illustrates one of many flaws in the U.S. Health Care System- when the sickest have to complicate their illnesses by possible if not likely financial stress, such as the case with biologic drugs discussed. Relief is needed for those of such great illness, and should be demanded by the public. Bills by both the house and senate were introduced to lawmakers in 2007. After all, why be so sick, and then be financially ruined during the last chapter of your life?
    Oh, and speaking of such administrations as the FDA, consider regulating those such as the previously mentioned anemia reps better so people will live a bit longer.
    Dan Abshear

  20. Innovation in Pharmacology in the form of Biopharmaceuticals
    Beginning in the 1970, biopharmaceuticals were being researched for conceptual production in those places once called academic institutions, and conducted basic research to identify new product candidates applying a great amount of research. The same protocol is applied with biopharmaceutical companies today.
    The first biopharmaceutical ever was synthetic insulin called Humulin made by Genetech in 1982 utilizing what is called rDNA technology, which also is used to produce human growth hormones. Later the rights were sold to Eli Lilly for this insulin. Biopharmas are distant and covert relatives of big pharma, yet become intimate with them more often now than ever before due to dry pipelines of big pharma- GSK and Roche in particular, yet most big pharma examine acquisition of biopharma companies for assured profit more than any other reason, they may speculate. Big pharma has a clear need to diversify which has created alignments with biopharmaceutical companies to create a pharmatech of sorts with the resources from both big pharma and biopharmaceutical companies. Furthermore, big pharma likes the fact that there is no design to produce biogenerics along with another fact that biopharmaceutical companies historically are fast growing companies of a different ethnicity of their own.
    Over 20 biopharma drugs were approved in 2005, I believe. They grew almost 3 times as much as big pharma recently. Last year, biopharmaceutical companies made close to 80 billion in sales as well. Over 20 biopharmaceutical products are blockbusters by definition. They are overall very effective treatments for very difficult diseases to manage, as they target specific aspects of certain diseases, which limits side effects experienced by the patient placed on therapy with a biopharma drug. Unlike traditional drug development, biopharmaceutical companies first seek disease targets by genetic analysis and then search for a way to manipulate this target in a very specific way. The biopharmaceutical companies typically have a high profit margin and their products. Also, these products are biologically synthesized and do not cross into the bloodstream.
    There are about a dozen f different classes or mechanisms of action of biopharmaceuticals that have about a half of dozen different types of uses that is always increasing, as lablel alterations of biopharmas are requested soon after the approval of a particular medication by this method that is allowed for further exploration of potential additional uses of thier new drug which, like other biopharmaceuticals, work in novel ways. Some cause apoptosis, or cell death of specific tumor cells. Some cause angiogenesis to occur, which means they cut off the blood supply to tumors. Then some biopharmaceuticals have multiple modes of action that benefit certain patient types and their diseases greatly, as with most biopharma products, the safety and efficacy is evident and reinforced with clinical data and eventual experience with the biopharmaceutical that is chosen to be utilized. And this clinical data is of a different method as well. Patients in the clinical trial are profiled, which allows better interpretation of this clinical data on their products.
    Some biopharmas are more noteworthy than others, such as Enbrel, which was originally created for the many forms of RA- arthritis caused by the patient’s immune system attacking their bodies. At one point, demand exceeded supply for this drug, as the efficacy and safety was evident and demand was unexpected by the manufacturer, so Enbrel was sought out by doctors and patients both due to the clinical data verifying the efficacy and benefits of the drug. Relief from the pain and decreased quality of life was the primary motivation for patients seeking this particular drug. Enbrel was approved in 1998 and produced from what are called monoclonal antibiodies, which is one of several ways in which biopharmaceuticals are produced. In fact, some call the 1990s the biopharmaceutical decade.
    Partnering of biopharmaceutical companies and larger pharmaceutical companies began during this decade in large part. Or a big pharma company will acaquire a biopharmaceutical company for complete ownership and bypass what would otherwise be a symbiotic relationship in that big pharma can provide the resources and connections necessary to launch and grow a particular biopharmaceutical drug, with the return on this investment being speculated revenue generated from what should be eventually a blockbuster biopharmaceutical.
    The country of Belgium provides the most biotech products to the biopharmaceutical companies in the United States, which leads the industry in the world, with more than 70 percent of both revenues and research and development expenditures. Canada is ranked number two in this area, I’ve been told.
    Some biopharmaceutical drugs are more profitable than others as well. Biopharmas compose around 10 percent of the pharmaceutical market presently, I understand. And with the government health care programs being the largest U.S. payers for pharmaceuticals, Medicare pays 80 percent of the cost of biopharmaceuticals. One other controversial, yet profitable biopharma class is known as EPOs, with names like Procrit and Epogen, and are indicated for anemia that is experienced in patients on dialysis or who have cancer in particular. Doctors are monetarily incentivized to exceed dosing requirements of these agents for their anemic patients, but this excess causes premature deaths and accelerated cancer progression for the patients that are over-dosed in this way. Once this tactic was exposed, there are now limitations regarding the amounts authorized to be given to particular patients placed on these EPOs. They are in the class of hormone biopharmaceutical drugs, which is another type of several classes of biopharmaceuticals, and they reduce the need for blood transfusions as they increase RBC proliferation.
    While biopharmaceuticals are very efficacious and safe, as well as having therapeutic and diagnostic benefits for the very sick, the cost of them is outrageous, some have said. Genzyme has one biopharma product that costs a half a billion dollars a year. Yet most biopharmaceuticals cost around 100 grand a year for therapy that provides with some only limited life extension or survival rate of these patents that is only a few months. Furthermore, with cancer drugs, they are used together with chemotherapy for their treatment regimens, so there is no real improvement in the quality of life of some patients on biopharmaceuticals, considering the devastating side effects of chemo treatment. In addition, Co-pays financially drain such patients and their families, yet there is no other choice for therapy because of the avoidance in the creation of generic biopharmaceuticals, for example. Oncology, by the way, is the primary commercial focus of biopharmaceutical companies now and in the immediate future, so maybe competition will be a cost advantage to such patients in time.
    Several years ago, I saw Roy Vagelos, former CEO of Merck, speak to others at Washington University in St. Louis. And during his presentation, he stated something similar regarding the cost of biopharmaceuticals and asked as well about whether or not the value related to the cost of biopharmaceticals appropriate for such a brief life extension of cancer patients in particular, for the most part. An issue or issues are always associated with new paradigms and innovations. Yet there are only a few biopharmaceuticals out of many available with debatable benefits with the high price tag. It ends up being what the market will bear. Yet the real question is the clinical evidence behind biopharmaceuticals: If a biopharmaceutical stops tumor progression without remarkable survival benefits or improvement in quality of life, is the price tag worth it to the patient? Assuring that a logical construct is examined to conclude that such a drug will be of benefit to a very sick patient will or should be the determining factor on the treatment regimen selected for such a patient.
    How do these drugs differ from typical drugs that have been made before this advent of biopharmaceuticals? Unlike the small molecule, synthetic, carbon based pharmaceuticals of yesterday, biopharmaceuticals, classified under what is called Red biotechnology due to this being a medical process in the biotechnology world, essentially are larger and very complex modified proteins derived from living biological materials that vary depending on what medication will be manufactured and for what disease state. In fact, it is difficult to identify the clinically active component of a biopharma drug, which is why there is no pathway for generic copies of such drugs, as it would require expensive and meticulous clinical trial processes. Yet recently, a company called Insmed demonstrated bioequivalence to Amgen’s Nupogen that increases whitle blood cells. While there still is no defined pathway for follow-on biologics, this study demonstrated that another biologic drug can show that it is therapeutically equivalent. Insmed’s drug in this study will not be available for marketing until next year or later, though.
    Also, a transformed host cell is developed to synthesize this protein that is altered and then inserted into a selected cell line. The master cell banks, like fingerprints, are each unique and cannot be accurately duplicated, which is why there are no generic biopharmas, yet biosimilar drugs are again a possibility, yet it’s in more of a conceptual phase presently, so it seems. So after this insertion, the molecules are then cultured to produce the desired protein for the eventual biopharmaceutical product. These proteins are very complex and are manufactured from living organisms and material chosen for whatever biopharma may be desired to be created. It is difficult to identify the clinically active component of biopharma drugs. So manufacturing biopharmas is a difficult process, and a small manufacturing change could and has raised safety issues of a particular biopharma in development that manufacturing had a manufacturing flaw of some sort. It takes about 5 years to manufacture a biopharmaceutical. And each class has a different method of production and alteration of life forms to create what the company intends to develop. Yet overall, their development methods are rather effective.
    Another difference is that biopharmas are regulated under what is called the Public Health Service Act, and unlike the FDA, they authorize the marketing of biopharmaceuticals. The Act’s role in monitoring the promotion of biopharmaceuticals is unknown. Safety protocols regarding biopharmaceuticals are a mystery to me as well. What is known is that biopharmaceuticals have the potential to discover therapies to treat the cause of a particular disease state instead of treating it symptomatically. They set out to solve unmet clinical needs by science that has yet to be proven. Biopharmaceutcals save, enhance, and extend the quality of life of patients with terrible diseases, and over 250 million people have benefited from their products.
    Presently, few biopharmaceutical companies are actually profitable. Also, with biopharmaceuticals, some years are better than others from a revenue point of view. Yet like any business, some years are better than others, and biopharmaceuticals are anticipated to offer quite a bit to public health in the future, with a focus on cancer patients in particular.
    The cost of developing a biopharmaceutical exceeds a billion dollars, with about a third actually making it to market. The market size of biopharmaceuticals is rapidly approaching 100 billion dollars a year, with average annual growth between 10 and 20 percent. Between70and 80 percent of cancer drugs are prescribed off-label, so it will be interesting on how these drugs will be used in such disease states now and in the future.
    Regardless of the challenges that are and will be faced by biopharmaceuticals, I’m pleased to see the results and realization of true innovation in pharmacology by taking a different path of drug development. Furthermore, I believe others should behave in a similar manner and be inspired by the biopharmaceutical companies and what they have done and continue to do for the benefit of the patients.
    “The progressive development of man is vitally dependent on invention.” — N. Tesla
    Dan Abshear (what has been written is based upon information and belief)

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