Today's Wall Street Journal has a refreshing interview with Dr. Susan Desmond-Hellmann, who is chancellor of the University of California, San Francisco, and a former drug industry research scientist. The piece begins with an introduction that says, "Many universities are wringing their hands over the increasing coziness of medical schools and their corporate partners. Susan Desmond-Hellmann ... has no such qualms."

As the introduction notes, "potential conflicts of interest are a growing concern at many schools." That's a problem. What matters are not "potential" conflicts of interest but actual conflicts that result in a researcher or clinician putting his or her own self interest over the interests of the patients whose well-being they manage.

Unfortunately, the fear of being branded with a scarlet letter "I" -- for industry ties -- has led far too many universities, scientists, and clinicians to pass up opportunities to collaborate with the drug and medical device industries in ways that might have redounded to the benefit of patients. Fortunately, while it is clear from the interview that Dr. Desmond-Hellmann takes genuine conflicts of interest seriously, she has rejected the narrow-minded attitude that paints all industry ties as inherently corrupting:

"WSJ: What do you tell professors who won't work with drug or biotech companies?
"Ms. Desmond-Hellmann: I think that's a huge mistake. If you're a professor now, and you want to get your discovery to society, you either need to start a company or work with a company to commercialize a product. When professors have told me they won't work with companies anymore because they feel they'll have this scarlet letter, I think: 'Wouldn't that be sad if all the best scientists and clinicians won't work with companies because the public has said they're evil?'"

Unfortunately, the published interview is rather short, so Dr. Desmond-Hellmann is never asked to discuss her views on what exactly makes for a conflict of interest. We know, for example, that not all conflicts of interest involve money. The literature is full of examples in which such motivations as raw ambition, the desire to achieve research successes or to be the first to discover some phenomenon, or simply a basic fear of failure created conflicts that contributed to fraudulent research and/or harm to an otherwise innocent third party.

As medical ethicist Sigrid Fry-Revere puts it, a conflict of interest is any "clash of competing interests in which a socially sanctioned goal could potentially be compromised by a more personal goal. Conflicts of interest exist in every form of human interaction. Therefore, the question should be not whether conflicts exist, but whether relevant individuals will succumb to the temptation to satisfy more immediate personal desires at the expense of long-term personal benefit and long-term social goals."

In short, conflicts can never be eliminated, though they can and should be managed. And Susan Desmond-Hellmann should be congratulated for approaching the issue of conflicts with an open mind, for expressing an understanding that industry-academy relationships need to be monitored, and for realizing that the benefits of partnering with industry generally far outweigh the risks that might arise from conflicts of interest.

The issue of bias was in the news again this week as the Wall Street Journal reported that "three of the advisers [at an advisory committee meeting to discuss four Bayer birth control pills] have had ties to Bayer, serving as consultants, speakers or researchers."

Bias can be a hindrance to good decision-making. Unfortunately, most of us have some biases, whether they are religious, political, philosophical, nepotistic, analytical, or economic.

Religious bias can affect one's views on contraceptives, the termination of pregnancy, and "pulling the plug" on seriously ill patients. Political bias arises when the decision maker tries to foster a favorable image or to support a particular party or politician. Philosophical bias can affect how we think about who should be treated, or whether certain conditions should be treated at all. Or, perhaps, whether drug companies should be allowed to profit by treating illness. Or, perhaps, whether actions are best taken through public or private organizations. Nepotism means giving advantages to friends or relatives. Individuals can be analytically biased by, for instance, confusing low-risk and high-risk situations or by lacking the right analytical tools to make good decisions. Economic bias is the most common target and was the subject of the Wall Street Journal article referenced above. It arises when a person can profit from a role as a supposedly impartial judge.

If the FDA was serious about bias, it would consider all kinds of bias--religious, political, philosophical, nepotistic, analytical, and economic--and set up systems whereby the expertise of experts could still be extracted while the effects of their biases was minimized.

"A bias recognized is a bias sterilized." -- Benjamin Haydon, British painter and writer

The FDA has come under fire yet again over allegations that a drug advisory panel decision was tainted by financial conflicts of interest.

Some recent research has suggested that women taking birth-control pills containing the active ingredient drospirenone -- such as the Bayer AG products Yaz, Yasmin, Beyaz, and Safyral, as well as several generic versions of the drug -- had roughly double the risk of non-fatal blood clots as those taking other oral contraceptives (see here and here). Last spring, Bayer issued a statement contesting the validity of the study methodology, and claiming that other research -- presumably more valid in Bayer's opinion -- found no heightened risk.

Who's right and who's wrong is a difficult question to answer. But at a December 9, 2011 joint meeting of the agency's Reproductive Health Drugs Advisory Committee and its Drug Safety and Risk Management Advisory Committee panelists sided with Bayer by a 15 to 11 vote that drugs containing drospirenone should remain on the market.

What's particularly noteworthy about the vote, however, is that an investigation by The Washington Monthly and the British Medical Journal has revealed that at least four of the committee members "have either done work for the drugs' manufacturers or licensees or received research funding from them." What's more troubling, though, is that the FDA did not itself make public any of these financial ties, and it took a couple of reporters to reveal the information.

By itself, the presence on FDA advisory panels of researchers who have done work funded by the drug industry is not problematic per se. After all, the purpose of the advisory panels is to provide the best possible expert advice, so the agency can better evaluate the benefits and risks of medicines. As Harvard Medical School researcher Thomas Stossel has explained over and over to anyone who'll listen, the manufacturers of drugs are going to seek out the best researchers with the most knowledge about a particular disease or condition to provide insights on their research and development programs. So, if you bar anyone with any financial ties to the industry from serving on regulatory advisory committees, that necessarily means settling for people who are not the best. Moreover, despite all the sturm and drang about financial conflicts of interest, and a growing literature examining the effects of these conflicts, "Evidence that relationships compromise scientific integrity is weak or false," and "there is no evidence at all about the effect of physician-industry relations on patient outcomes."

Nor am I especially concerned about the narrowness of the vote in this particular case. The Washington Monthly/BMJ report tries to make an issue of the fact that, without the four conflicted panel members, the result would have been an 11 to 11 tie. That still leaves us essentially where we were previously -- that is, with conflicting evidence and an essentially evenly split panel vote elucidating the fact that, with many drugs, it's difficult to tote up the benefits and risks and make a well-reasoned decision.

More importantly, though, those decisions are left to the FDA, not the advisory committees. By all accounts, the FDA was in fact aware of the financial conflicts. And the agency itself is fully capable of evaluating the full weight of scientific evidence and discounting the advisory committee's decision if deems those financial ties to have affected the votes of various members. The agency often does side with advisory committees in its approval or disapproval decisions. But there are far too many cases in which the agency rejected an advisory committee recommendation (almost always in the direction of rejecting approval for a drug that an advisory committee recommended approving) to think that the committee votes are anything more than what they purport to be: advisory in nature.

What I do find troubling about the whole affair, however, is the fact that the financial relationships were not previously disclosed by the FDA. There is nothing especially pernicious about these financial arrangements. But full information disclosure by federal agencies serves an important function: It lets the public evaluate the performance of our regulatory overseers. Sometimes information disclosure can be used more to intimidate and demagogue public and private actors -- and that is a tendency to be feared. But when it comes to government decision making, we ordinarily should prefer more information to less. In the end, disclosing not just potential financial conflicts of interest, but also other conflicts (such as intellectual ones) is a far better approach than excluding experts from fully participating in the regulatory process. And in that regard, The Washington Monthly and BMJ should be congratulated for their work.

Recently it has become common in my consulting practice for one of my clients to say, "I can't believe that so-and-so wasn't a member of that recent FDA advisory committee." So-and-so being a renowned expert in the field. The reason for this person's absence was his or her ties to the pharmaceutical industry coupled with the FDA's emphasis on preventing potential conflicts of interest in advisory committees.

The FDA is supposedly a scientific organization that makes decisions based on empirical data. A drug company can't simply approach the FDA and say, "Theoretically, this should work," and expect FDA approval for a new drug. The FDA wants to see empirical evidence. Unfortunately, the FDA applies this standard to other groups, like drug companies, but not to itself. When it comes to potential conflicts of interest among advisory committee members, the FDA has simply rounded up the usual suspects and declared them guilty without so much as a trial. Why would the FDA need empirical evidence when the problems with conflicts of interest are so obvious?

Well, I do happen to have some empirical evidence in this arena and it comes from Sidney Wolfe, one of the pharmaceutical industry's most vehement critics. David R. Henderson and I wrote an article about it in early 2009.

In a 2006 study to look at potential conflicts of interest, where outside FDA advisors had ties to industry, Wolfe and four other authors published an article in the Journal of the American Medical Association that drew on 76 product-specific meetings of FDA advisory committees that involved yes or no votes on individual drugs.

Industry critics like Marcia Angell have created an entire cottage industry of conferences and books devoted to decrying the "conflicts of interest" that for-profit drug and medical device industries supposedly inject into the otherwise "hallowed" halls of pure academic research. Get the dirty money out, or so the argument goes, and the angels of academia (pun intended) will be returned to rightful control of the academy.

Not so fast. A fascinating article in the Wall Street Journal today airs some the "dirty" laundry of academic medicine: many of the attention grabbing results published in top-flight medical journals, sans industry influence, can't be reproduced independently by "greedy" pharmaceutical companies.

From the Journal:

This is one of medicine's dirty secrets: Most results, including those that appear in top-flight peer-reviewed journals, can't be reproduced. "It's a very serious and disturbing issue because it obviously misleads people" who implicitly trust findings published in a respected peer-reviewed journal, says Bruce Alberts, editor of Science. On Friday, the U.S. journal is devoting a large chunk of its Dec. 2 issue to the problem of scientific replication.

Reproducibility is the foundation of all modern research, the standard by which scientific claims are evaluated. In the U.S. alone, biomedical research is a $100-billion-year enterprise. So when published medical findings can't be validated by others, there are major consequences. Drug manufacturers rely heavily on early-stage academic research and can waste millions of dollars on products if the original results are later shown to be unreliable. Patients may enroll in clinical trials based on conflicting data, and sometimes see no benefits or suffer harmful side effects. There is also a more insidious and pervasive problem: a preference for positive results.

Eliminating financial conflicts of interest from medicine is the new gospel of pure science. Not so fast: Who watches the watchmen? All human beings are fundamentally self-interested, and declaring freedom from an obvious financial conflict can merely mask other, equally problematic (but more subtle and thus dangerous) conflicts.

As anyone who's spent time in grad school knows, academia is a really a jungle red in tooth and claw. In academic medicine the spoils of high profile publications include tenure, lucrative lab assignments and government grants, and the accolades from your peers that come with the New York Times picking up the headline from your latest Lancet or New England Journal of Medicine article.

Ironically, medical journals - often at the forefront of decrying industry bias - are part of the problem, since they too compete fiercely for subscriptions and ad revenues, and seek out "splashy" headlines with big health implications that they then peddle to major media publications. From a scientific standpoint, studies that disprove their hypotheses are at least as valuable as positive ones, but they just don't get published. Or as Atlas' Venture's Bruce Booth told the Journal, "nobody gets a promotion from publishing a negative study."

In fact, there's a good case to be made that market incentives and government regulations enforce a much higher standard of scientific credibility on firms than on individual academics. Companies have to submit all of their studies and data (positive or negative) to the FDA, and must usually complete two successful "blinded" and placebo-controlled studies for FDA approval.

Academic researchers, on the other hand "rarely conduct experiments in a 'blinded manner' [which] makes it easier to cherry-pick statistical findings that support a positive result." Bayer has reported that it has "halted nearly two-thirds of its early drug target projects because in-house experiments failed to match claims in the literature," including those from the "most prestigious journals."

Bayer's approach is unsurprising: companies have powerful incentives to weed out bad science quickly, since the pivotal clinical trials for FDA approval (called Phase III trials) can cost hundreds of millions of dollars and take years to complete. So you'd much rather kill a bad idea quickly, and cheaply, than let it get too far along in development (although, sadly, this happens all too often in the industry anyway just by virtue of the underlying scientific uncertainty).

So where does this leave us? Companies might be biased, academic scientists might be biased, and the system is rife with incentives to promote you career or your product at the expense of good science.

Should we just close up the whole enterprise? Go back to bloodletting and herbal tea?

Not at all. We don't need men to become angels to produce good science or good government. Demanding disclosure of appropriate potential conflicts, seeking peer review from a wide-range of experts with varying opinions, and keeping a healthy skepticism about the latest scientific fads (even if they're published in leading journals) are all good checks on the spread of bad data.

And despite all hand wringing about conflicts of interest, the system has worked well for decades - producing incredible new treatments for AIDS, heart disease, and cancer. We cannot eliminate conflicts - and shouldn't even try to - but they can be managed appropriately. Indeed, self-interest, harnessed through market competition, can be an immensely powerful tool for good:

The principle of self-interest rightly understood is not a lofty one, but it is clear and sure. It does not aim at mighty objects, but it attains without excessive exertion all those at which it aims. As it lies within the reach of all capacities, everyone can without difficulty learn and retain it. By its admirable conformity to human weaknesses it easily obtains great dominion; nor is that dominion precarious, since the principle checks one personal interest by another, and uses, to direct the passions, the very same instrument that excites them.

The principle of self-interest rightly understood produces no great acts of self-sacrifice, but it suggests daily small acts of self-denial. By itself it cannot suffice to make a man virtuous; but it disciplines a number of persons in habits of regularity, temperance, moderation, foresight, self- command; and if it does not lead men straight to virtue by the will, it gradually draws them in that direction by their habits. If the principle of interest rightly understood were to sway the whole moral world, extraordinary virtues would doubtless be more rare; but I think that gross depravity would then also be less common. The principle of interest rightly understood perhaps prevents men from rising far above the level of mankind, but a great number of other men, who were falling far below it, are caught and restrained by it. Observe some few individuals, they are lowered by it; survey mankind, they are raised.

Lilly is facing a $13 billion dollar patent cliff in the next three years - but CEO John Lechleither explains to Xconomy that increasing R&D spending, rather than chasing mergers, will better help the company weather the storm in the long run.

U.S. Senator Claire McCaskill (D, MO) is calling for the Department of Health and Human Services to investigate the Obama's Administration's award of a $433 million dollar sole source contract to a company owned by billionaire Ronald Perelman, who also happens to be a "major democratic donor." The company, Siga Technologies, is set to make an antiviral drug for smallpox that cannot be tested or approved for use in humans, according to the FDA. For more on this, see my earlier commentary here and the L.A. Times, here.

Robert Samuelson looks at recent OECD data comparing health care costs and outcomes in the U.S. to other wealthy nations, and says the data paints a "devastating picture" of U.S. health care. For another view of the OECD data, at least on life-expectancy, see Avik Roy's excellent post here.

The A.P. reports a sobering picture of more parents "opting out" of having their children vaccinated for school. Health officials fear that the trend could lead to a resurgence of diseases that haven't been seen in the U.S. in decades, like polio.

Earlier this week, U.S. Senator Al Franken (D, MN) and Senator Lamar Alexander (R, TN) released draft legislation that would, among other things, relax the FDA's conflicts of interest standards to better ensure that the agency can get timely access to the expert advice it needs to approve new medicines and medical devices.

From the press release:

"After speaking with countless patients, doctors, and members of the medical device industry in Minnesota, I've learned that certain barriers in the regulatory process are making it harder to get patients the medical devices they need," said Sen. Franken. "My legislation would remove unnecessary barriers so that these critical medical devices get to the patients that need them as quickly and safely as possible."

Bipartisan FDA reform efforts seem to be breaking out all over Congress.

Check your local zoo. The lions may be lying down with the lambs.

An enormous, no-bid government contract went to Siga, a small biotech company, one of whom's biggest shareholders just happens to be leading Democratic billionaire and donor, Ronald Perelman.

Courtesy of the L.A. Times:

Senior officials have taken unusual steps to secure the contract for New York-based Siga Technologies Inc., whose controlling shareholder is billionaire Ronald O. Perelman, one of the world's richest men and a longtime Democratic Party donor.

When Siga complained that contracting specialists at the Department of Health and Human Services were resisting the company's financial demands, senior officials replaced the government's lead negotiator for the deal, interviews and documents show.

When Siga was in danger of losing its grip on the contract a year ago, the officials blocked other firms from competing.

Siga was awarded the final contract in May through a "sole-source" procurement in which it was the only company asked to submit a proposal. The contract calls for Siga to deliver 1.7 million doses of the drug for the nation's biodefense stockpile. The price of approximately $255 per dose is well above what the government's specialists had earlier said was reasonable, according to internal documents and interviews.

More on this from Ed Silverman, at Pharmalot, and Michelle Malkin, at NRO.

The New York Times has an long article today on how some federal health care panels creating new treatment guidelines have - gasp - experts on them who have work with or consulted for drug companies.

Critics like David Rothman believe that no one who works with companies to create better treatments for patients should have a voice in discussions over how to use those tools (and others) more effectively:

"Consciously or not, they may well be making decisions that fit their funders, their payers and not the patient's best interests," said David J. Rothman, president of the Institute on Medicine as a Profession, a nonprofit center affiliated with Columbia University. "If you want the public to really believe in the guidelines, why not have a committee that is conflict-free?"

So if you've worked for a company, "consciously or not", your expert opinion is automatically compromised. An interesting point of view, and certainly a very powerful rhetorical tool for disqualifying anyone who disagrees with you. I believe the Marxists would've called it "false consciousness."

Would the Times' definition of bias also extend to excluding teachers from curriculum design panels at colleges and universities (obviously they have a financial incentive to get more students in their classes), lawyers or judges from serving in Congress or advising on legal panels (creating more lawsuits, which they are then paid to litigate), or for that matter, having any practicing physicians serve on any health advisory committees at all (doctors make money by seeing sick people!).

The Times' definition of "bias" is strangely limited to "commercial" bias, i.e., working for corporations, and completely ignores other forms of bias: from profession, education, experience (or lack thereof), ideology, etc. Commercial bias is an important form of potential bias, but it is far from the only potentially significant one.

For instance, when the federal government decides not to cover mammograms or prostate cancer tests for certain groups of patients, it saves money. Isn't that a bias?

We live in a world of potential bias (is the New York Times reporter biased against corporations?), but we find ways of managing them - through disclosure, and through ensuring a diversity of viewpoints and experience like the committees organized by the NIH.

Of course, the goal of the crusaders against commercial bias isn't to rid the world of all bias...just the points of view that they might disagree with.

How biased is that?

Who says bipartisanship is dead?

U.S. Senators Michael Bennet (D, CO), Richard Burr (R, NC), and Amy Klobuchar (D, MN) have proposed legislation that would (among other things) rescind onerous conflict of interest rules for FDA advisory committees enacted in 2007.

FDA Commissioner Margaret Hamburg, among others at the FDA, have admitted that the current COI regime makes it difficult for the agency to recruit the most qualified experts for its advisory committees.

Kudos to Senators Bennet, Burr, and Klobuchar, for working across partisan lines to fix a serious problem that prevents the FDA from getting access to the best scientific advice available. The new legislation would merely require the FDA to be subject to the "same conflicts of interest requirements as the rest of the federal government."

For more on how excessive conflict of interest regulations are impeding innovation, see this paper by noted NYU law professor Richard Epstein, and this post I wrote for National Review.

The Medical Progress Today blog provides a forum for economists, scientists, and policy experts to explore the scientific, regulatory, and market frameworks that will best support 21st century medical innovation.  We will focus especially on the U.S. Food and Drug Administration, the agency responsible for overseeing the nearly half-trillion dollar drug and medical device markets in the United States.

The blog will range widely in terms of topics and POV.  But, at its heart, MPT is about harnassing the power of science, market incentives, and (prudent) regulation to create the kind of health care system that we all want - more effective, efficient, and affordable.

We live in a time of breathtaking advances in the capacity to treat--and cure--illness. The translation of the human genome and an explosion of information from new sciences like metabolomics and proteomics have given researchers powerful new tools for understanding, treating and (eventually) curing deadly diseases like cancer and Alzheimer's. The old medical paradigm treated illnesses symptomatically with one-size-fits all medicines; the new paradigm will analyze disease at its molecular roots and to develop personalized therapies that match a patient's own unique biochemistry.

The question is not whether personalized medicine will become a reality, but when. Innovation is currently struggling in the face of regulatory, reimbursement, and insurance frameworks built around public health assumptions that fit the middle of the last century, rather than the first decades of the 21st century.

Turning personalized medicine from an aspiration into a reality will require regulators, companies, and researchers to breakdown binary regulatory frameworks; develop collaborative approaches to rapidly validate new technological standards; and embrace clinical tools that allow patients and physicians to become full partners in the innovation process.

Through both this blog site and the original essays it will commission, MPT will provide a forum to explore the most current ideas--and emerging challenges--in the field of personalized medicine.

We hope that you will find MPT a vital and provocative resource for building a health care system ready to embrace the full potential of personalized medicine and sustain U.S. leadership in biomedical innovation.

Recently, the New York Times ran an article on the new dean of Weill Cornell Medical Center, Dr. Laurie H. Glimcher.  The article implied - or at least strongly hinted - that some impropriety or at least suspicion should attend her appointment because she has "strong ties to the pharmaceutical industry."

The new dean, Dr. Laurie H. Glimcher, 60, who has ties to the pharmaceutical giants Merck and Bristol-Myers Squibb as well as to scientific and biotechnology companies, said she wanted to use her experience to forge partnerships with both the public and private sectors.

Dr. Glimcher, an immunologist with a strong interest in osteoporosis, defended her outside interests, saying they presented no conflict as long as they were transparent. She said she wanted to "leverage the strengths of everyone," whether scientists, pharmaceutical companies or biotechnology companies. "There should be no silos between all of these different strengths," she said.

The tragedy is that Dr. Glimcher has to defend her involvement with "outside interests" who bring lifesaving new treatments to patients. It is imperative that academic and industry scientists collaborate in the process of translating new basic science discoveries into innovative new treatments for patients.