An Inconvenient Woman » Big Pharma Watch

Big Pharma Lobbying Money Influencing American Healthcare Reform

H. Sandra Chevalier-Batik — Tue, 14 Jul 2009 19:45:05 +0000

Money Makes The Healthcare Reform Bill Turn Around

Last month, Jim Edwards of BNET PHARMA revealed how much cash is involved to influence the outcome of the Obama Healthcare Reform bill. Big Pharma Lobbying Bucks are raining down on Washington. Congressional representatives and members of the Obama administration have to at least consider the Industries requests…after all, Big Pharma, at $1.6 billion since 1998, represents the number ONE all-time spender on lobbying.

If, and when, any of our elected representatives, actually reads the Health Reform Bill being pushed through by Madam Speaker, Pelosi, they’ll probably find Big Pharma wish list items like:

Pharmaceutical and health product companies, like the insurance industry, strongly oppose any proposal to create a public health insurance option, fearful that private insurers would be marginalized and government price controls would limit what the industry can charge for its products.

Medicaid, which provides insurance to poor families, expanded to cover more low-income workers. This would mean more people could afford drugs and medical devices, increasing the industry’s target market.

Big Pharma supports the mandate that all Americans purchase health insurance, boosting the industry’s customer base by millions.

If and when, The Obama Administration keeps its promise to post the Health Care Reform Bill on the Internet for public review, be an example to the Congress read it; discuss it; make suggestion to your representative. Who knows maybe your rep is one that care more about representing view of the folks that voted for him, the Big Pharma lobbyists that donate big bucks to his favorite charity, or offered his wife a job.

As President Obama waits for Congress to deliver a heathcare reform bill, pharmaceutical companies are spending millions on lobbyists to thwart any measure that might make drug prices cheaper or even allow the government to negotiate them, according to the Center for Responsive Politics. Companies spent 41 percent more this year on lobbying than last, USA Today reported.

A look at company lobbying reports by the Associated Press shows companies aligned in lockstep against price controls, allowing Medicare and Medicaid to negotiate prices, or drug reimportation.

And companies have laden Congress members with campaign donations, funds to their non-profits, and paid seats on their boards. Taken together, it looks like Congress is bought and paid for. Thus millions of Americans may be entertaining a false hope that Washington will deliver a plan that will lift U.S. healthcare out of its Third World status and into something approaching modernity, like Europe or Canada. An example, from The Boston Globe:

The wife of Senator Chris Dodd, who is in charge of writing the Senate’s bill, sits on the boards of four healthcare companies.

Many other lawmakers own thousands in stock or recieve more in compensation to sit on pharma company boards. The Washington Post has a comprehensive list of money ties between congressmen and drug companies:

Almost 30 key lawmakers helping draft landmark health-care legislation have financial holdings in the industry, totaling nearly $11 million worth of personal investments in a sector that could be dramatically reshaped by this summer’s debate.

And a USA Today report details how drug companies keep politicians’ pet charities funded:

Health care groups, for instance, give millions to the planned Edward M. Kennedy Institute for the United States Senate in Boston. Pharmaceutical giant Amgen wrote the biggest check — $5 million in December — to the institute, which will honor Kennedy’s more than four decades in Congress and promote the study of the U.S. Senate.

Here, compiled by the AP, are individual company details about the lobbying activities in Q1 2009:

PhRMA – $7 million
PhRMA is again trying to ensure drug companies won’t face steep cuts in prescription prices and, instead of reducing drug margins, have proposed cost reductions to hospitals and insurers.
Pfizer – $6.1 million
Pfizer … more than doubled its lobbying spending from the year-ago period. The company also spent nearly $3.3 million lobbying in the fourth quarter of 2008.
New York-based Pfizer lobbied on legislation on health reform initiatives, electronic prescriptions, veterans issues, allowing generic versions of expensive biologic drugs and a proposal requiring research comparing the effectiveness of different medical treatments.
It also lobbied on U.S. patent reform and on international patent, trade and regulatory issues involving more than 20 countries; national health insurance; legislation to require drug makers to disclose payments to physicians; reauthorization of the State Children’s Health Insurance Program; and environmental issues related to pharmaceutical manufacturing.
Eli Lilly – $3.4 million
Domestically, the drugmaker lobbied on Medicaid rebates and advertising transparency.
Amgen – $2.8 million
Amgen Inc., the world’s largest biotechnology company, spent nearly $2.8 million lobbying in the first quarter as Congress debates a potential system for bringing less expensive copies of pricey biotech drugs to the market.
Merck – $1.5 million
Merck lobbied Congress and the White House on health care reform issues including increasing coverage for uninsured people, requiring research comparing the effectiveness of different medical treatments and keeping a private-sector health care system.
… and increasing funding for the national immunization program for low-income children.
Merck lobbied against imposing government price controls on prescription drugs bought under the Medicare program and against expanding rebates paid to the government for medications bought under the Medicaid program. But it lobbied for ensuring access to vaccines under Medicare; it sells the Zostavax vaccine against shingles, a painful, blistering rash that generally strikes senior citizens.
Johnson & Johnson – $1.5 million
It lobbied on multiple bills involving the Medicare prescription drug program that would either limit discounts given to the government or lower the prices it pays.
J&J which offers employee wellness programs, lobbied in support of a tax credit to employers who do so, and on a bill that would require drug and medical device makers to report many payments to physicians.
Wyeth – $876,000
Madison, N.J.-based Wyeth ( WYE - news - people ) lobbied on several aspects of health care reform, including bills that could limit the prices the government pays for medications, as well as public disclosure of drugmaker payments to doctors. It lobbied on drug advertising rules and legislation to modernize the Food and Drug Administration.
The maker of Centrum vitamins also lobbied on dietary supplement issues.
Schering-Plough – $600,000
Schering-Plough lobbied on health reform issues including access to coverage, price rebates for drugs bought under the Medicaid program and proposals to require research comparing effectiveness of different medical treatments.
The maker of allergy treatments Nasonex and Claritin, and the HomeAgain Pet Recovery System also lobbied on reauthorization of the Children’s Health Insurance Program, legislation affecting Food and Drug Administration operations, and against importation of cheaper prescription drugs from foreign countries, which domestic drugmakers have opposed for years.
Amylin – $350,000
San Diego-based Amylin lobbied on legislation that would allow the Food and Drug Administration to approve copies of biotech drugs, reimbursement issues, drug safety and physician payment disclosures.
Biogen – $290,000
The Cambridge, Mass.-based company lobbied on legislation that would set up a process for the Food and Drug Administration to approve biosimilars, or copies of biotech drugs.

Jim Edwards, a former managing editor of Adweek, has covered drug marketing at Brandweek for four years, and is a former Knight-Bagehot fellow at Columbia University’s business and journalism schools.
Email Jim Edwards or follow him on Twitter.

BNET Pharma provides daily industry news coverage and insights for managers and executives about the major manufacturers of pharmaceuticals and medicine. In addition to detailed company profiles, we bring you critical analysis on new alliances and partnerships, new patents and products, mergers and acquisitions, cost management, investments and deal flow, and a host of other important business issues.

Image by Flickr user AMagill, CC

FDA is Finally Prosecuting Off-Lable Marketing of Pharmaceuticals

H. Sandra Chevalier-Batik — Thu, 25 Jun 2009 05:38:37 +0000

The United States Attorney’s Office

District of Massachusetts

FOR IMMEDIATE RELEASE
JUNE 18, 2009
WWW.USDOJ.GOV/USAO/MA

CONTACT: CHRISTINA DiIORIO-STERLING
PHONE: (617)748-3356
E-MAIL: USAMA.MEDIA@USDOJ.GOV

PHARMACEUTICAL COMPANY MANAGER SENTENCED FOR OFF-LABEL MARKETING

BOSTON, MA – A Branchburg, NJ, woman was sentenced today for violating the Food, Drug and Cosmetic Act, for marketing the drug Bextra for uses and dosages that were not approved by the Food and Drug Administration.

Acting United States Attorney Michael K. Loucks; Warren T. Bamford, Special Agent in Charge of the Federal Bureau of Investigation, Boston Field Division; Susan J. Waddell, Special Agent in Charge of the Department of Health and Human Services, Office of Inspector General; Leigh-Alistair Barzey, Resident Agent in Charge of the Defense Criminal Investigative Service; Kim A. Rice, Special Agent in Charge of the U.S. Food and Drug Administration, Office of Criminal Investigations, Metro Washington Field Office, Special Prosecution Staff; Jeffrey Hughes, Special Agent in Charge of the U.S. Department of Veterans Affairs, Office of Inspector General, Office of Investigations – Northeast Field Office; and Joseph Finn, Special Agent in Charge of the United States Postal Service, Office of Inspector General, Boston Field Office, announced today that MARY HOLLOWAY, age 47, of Branchburg, New Jersey, has been sentenced by United States Magistrate Judge Judith Dein to pay a $75,000 fine and twenty-four months of probation after pleading guilty to an Information charging her with distribution of a misbranded drug.

At the plea hearing, prosecutors told the Court that, had the case proceeded to trial the Government’s evidence would have proven, the following:

From approximately November 2001, through April 2005, HOLLOWAY was employed as a Regional Manager at a pharmaceutical company and was responsible for sales in her region of the drug Bextra. Bextra was a Cox-II inhibitor and had been approved in by the Food and Drug Administration (FDA) in November 2001 for the signs and symptoms of osteoarthritis, adult rheumatoid arthritis, at 10 mgs and primary dysmennorhea at 20 mgs, twice a day as needed. In 2001, the FDA specifically denied the request of the pharmaceutical company to approve it for acute pain, including the pain of surgery. The FDA told the pharmaceutical company that it could not approve it for these other indications because the safety in these other uses had not been established. Specifically, the FDA was concerned about the results of a study in which there was an excess of cardiovascular events in patients who had undergone coronary artery bypass graft surgery and used Bextra.

HOLLOWAY was aware of the FDA’s safety concerns, but that she nonetheless had her sales staff of approximately 100 employees sell Bextra for precisely the uses that the FDA refused to approve. For example, HOLLOWAY trained and encouraged her sales teams to promote Bextra by obtaining protocols from doctors that instructed that Bextra be used for the pain of surgery, an unapproved use, and at 20 mgs, an unapproved dose. HOLLOWAY also instructed her staff to market Bextra for use before, during and after surgery to reduce the risk of deep vein thrombosis, which is a form of life threatening blood clots, even though she knew there were no studies showing that Bextra was safe and effective for this use. Finally, HOLLOWAY encouraged her staff to make false safety claims about Bextra in order to sell the drug.

Acting United States Attorney Michael K. Loucks said, “We will continue to hold individuals responsible for their conduct in promoting pharmaceutical drugs outside of the uses for which they have been found to be safe and effective by the United States FDA. The conduct at issue here undermined the FDA’s regulatory scheme and put patients at risk for the purpose of pursing profits for the individual and the pharmaceutical company.”

Bextra was withdrawn from the market in April 2005.

The case was investigated by the Federal Bureau of Investigation, the Office of Inspector General for the Department of Health and Human Services, Special Prosecutions Staff for the U.S. Food and Drug Administration, Office of Inspector General for the Department of Veterans Affairs, the Defense Criminal Investigative Service, and the Office of Inspector General for the United States Postal Service. It was prosecuted by Assistant U.S. Attorneys Sara Miron Bloom and Susan M. Poswistilo of Loucks’ Health Care Fraud Unit.

Institute of Medicine Calls for Doctors to Stop Taking Gifts From Drug Makers

H. Sandra Chevalier-Batik — Mon, 22 Jun 2009 20:02:34 +0000

IOM Issues A “Scolding, Stinging and Damning” Report Concerning Financial Conflicts of Interest in American Medicine

The Institute of Medicine has issued a “scolding,” “stinging,” and “damning” report about financial conflicts of interest in American medicine involving pharmaceutical, medical device, and biotechnology companies.

If enacted, the IOM recommendations will essentially sever the financial ties that bind American medicine–its practitioners, researchers, academic institutions, journals, professional association and so-called “advocacy groups” from industries that have derailed American medicine from its humanitarian public mission.

Dr. David Rothman, whose Institute on Medicine as a Profession at Columbia University (which is bankrolled by financier George Soros) is quoted saying:
“With the I.O.M.’s endorsement, issues that were once controversial now are indisputable; conflicts of interest in medicine are no longer acceptable.”

Most important, the IOM report calls upon Congress to pass legislation that would require drug and device makers to publicly disclose all payments made to doctors–thereby lending important support for the Physician’s Payment Sunshine Act, sponsored by Senators Charles E. Grassley, and Herb Kohl who head the Senate Finance Committee that would do just that.

The IOM report acknowledges that:

“financial ties between medicine and industry may create conflicts of interest. Such conflicts present the risk of undue influence on professional judgments and thereby may jeopardize the integrity of scientific investigations, the objectivity of medical education, the quality of patient care, and the public’s trust in medicine. Recent news stories have documented troubling interactions between industry and physicians, researchers, and medical institutions.”

Though not identified, many of those news stories laid bare gross and pervasive financial conflicts of interest by psychiatry’s leadership, its professional associations, diagnostic and therapeutic practice guidelines, and the academic institutions they are affiliated with–all have been shown to be tainted by industry’s tentacles. In no other field of medicine have doctors sworn to “do no harm” knowingly prescribed toxic drugs that carry warning labels about induce suicide, metabolic syndrome, diabetes, and cardiac death.

Recently, Gabriel Myers, a seven-year old boy committed suicide. The child was treated by a “board certified” child psychiatrist in Florida who prescribed four psychotropic drugs for the boy including: the antidepressant, Lexapro, the antipsychotic, Zyprexa, and Eli Lilly’s deadly combination Symbiax (Zyprexa and Prozac). These three drugs were not approved for use in children though they are recommended by the most influential industry-paid child psychiatrists–all carry Black Box warnings which the treating psychiatrist ignored.

Clearly, the IOM committee–including the deans of Emory University and Stanford University who served as external reviewers of the draft report, according to Dr. Bernard Carroll–now recognize that financial relationships with industry are extensive and self-regulation by academic institutions has failed to rein in the most serious conflicts of interest. Indeed, as Dr. Carroll notes on his blog, HealthCareRenewal, both of these deans were confronted with evidence uncovered by the Senate Finance Committee that their institutions’ prominent (now former) chairmen of psychiatry were shown to have multi-million dollar undisclosed financial interests that posed serious conflicts of interest undermining both human subject safety and the integrity of the research findings.

To combat the current state of confusion created by variable conflict of interest policies adopted by various academic institutions, journals and professional societies, the IOM committee recommends a real universal overhaul that would prohibit financial ties between industry and researchers conducting human research; end industry funding for continuing medical education programs (within two years); end industry payments physician practice guidelines:

“Congress should create a national reporting program that requires pharmaceutical, medical device, and biotechnology companies to make public all payments to physicians, researchers, health care institutions, professional societies, patient advocacy and disease groups, and providers of continuing medical education. Public reporting will enhance accountability by allowing academic medical centers, medical journals, and others to verify disclosures made to them by faculty members, article authors, and others.”

Research: “as a general rule, that researchers should not conduct research involving human participants if they have a financial interest in the outcome of the research, for example, if they hold a patent on an intervention being tested in a clinical trial. The only exceptions should be if an individual’s participation is judged to be essential for the safe and appropriate conduct of the research.”

Continuing medical education: “a broad-based consensus process to develop a new system for funding high-quality accredited continuing medical education that is free of industry influence….”a new system of funding … should be developed that is free of industry influence.”

Community physicians: “should also follow the restrictions described previously regarding gifts, including meals, from companies; presentations or articles whose content is controlled by industry; meetings with sales representatives; and use of drug samples.”

Clinical practice guidelines: “influence physician practice, quality measures, and insurance coverage decisions. Given this influence, clinical practice guidelines need to be developed with greater transparency and accountability.

“The committee recommends that professional societies and other groups that develop practice guidelines not accept direct industry funding for guideline development and generally exclude individuals with conflicts of interest from the panels that draft the guidelines

“To reduce the risk for bias within the learning environment, academic medical centers and teaching hospitals should prohibit faculty from accepting gifts, making presentations that are controlled by industry, claiming authorship for ghost-written publications, and entering into consulting arrangements that are not governed by written contracts for expert services to be paid for at fair market value.”

The committee also recommends that: “the Department of Health and Human Services develop a research agenda to create a stronger evidence base for future conflict of interest policies. Such research should evaluate the impact of conflict of interest policies, including both desired outcomes and possible unwanted consequences.”

“Decisions about biomedical research, medical education, and patient care directly affect the public’s health. The public needs to be able to trust that physicians’ decisions are not inappropriately influenced by their financial relationships with industry.”

Although the IOM does not have the power to enforce its recommendations, the Institute usually carries great weight within the medical profession and health-care industry.

Sources: IOM. Conflict of Interest in Medical Research, Education, and Practice
REPORT BRIEF • APRIL 2009 http://www.iom.edu/Object.File/Master/65/981/COI report brief for web.pdf

See also, Peeling the onion: Is more conflict of interest disclosure getting us closer to the truth?
April 24, 2009 | Shelley Wood, The Heart.org WebMD:

Big Pharma Offers Financial Help For Comprehensive Health Care Reform

H. Sandra Chevalier-Batik — Mon, 22 Jun 2009 19:02:51 +0000

How Much Input to The Administration and Congress’ Health Reform Plan Will Big Pharma’s $80B Pledge to Health Reform Buy?

As I read Tracy Staton ‘s Fierce Pharma report about Big Pharma’s $80BILLION pledge, that was the first question that came to mind. Apparently wanting to give the Health Care Reform a boost, Drugmakers have agreed to foot the bill for $80 billion in Medicare drugs over the next decade. Some portion of that will benefit Medicare recipients, who, as you know, are on the hook for several thousand dollars’ worth of meds annually during the “donut hole” coverage gap. Some other portion will lower the cost of health reform, probably via bigger rebates to Medicare.

For thise of us who have not got our heads around the REALLY BIG BUDGET NUMBERS Washington is throwing around these days, $80 billion is less than one-tenth the projected cost of healthcare reform. But by striking this cost-sharing deal with one of the reform effort’s leaders–Sen. Max Baucus–and the White House, drugmakers could shame other providers into cutting their prices, too. Lawmakers will be able to twist some healthcare arms more forcefully, now that pharma has made this deal. And by delivering real, live cost-cutting, the reformers will be able to neutralize critics’ most tangible beef: That reform costs too much.

AARP is set to endorse the deal today at the White House, along with the President, who’s already praised the agreement and called it a “turning point” in reform efforts. PhRMA was quick to pat itself (and the industry) on the back for the savings: “America’s pharmaceutical research and biotechnology companies are signaling their strong support for these critically important efforts,” CEO Billy Tauzin said in a statement. This is a once-in-a-lifetime opportunity and, working together, we can make this hope for a better tomorrow a reality today.” Whether this deal will help drugmakers avoid greater revenue losses to healthcare reform remains to be seen. The full PhRMA press release is posted below.

Pharmaceutical Research and Manufacturers of America (PhRMA)Statement on Medicare Part D Coverage Gap

WASHINGTON, June 20 /PRNewswire-USNewswire/ — Pharmaceutical Research and Manufacturers of America (PhRMA) President and CEO Billy Tauzin and PhRMA Board Chairman David Brennan, Chief Executive Officer, AstraZeneca, issued the following statement regarding today’s commitment, as part of health care reform, to help close the coverage gap in the Medicare prescription drug program (Part D):

“PhRMA is committed to working with the Administration and Congress to help enact comprehensive health care reform this year. We share a common goal: every American should have access to affordable, high-quality health care coverage and services.

“As part of that reform, one thing that we have agreed to do is support legislation that will help seniors affected by the coverage gap in the Medicare prescription drug benefit. Although the program has been a tremendous success for the vast majority of seniors, the coverage gap has posed a challenge to some seniors and our companies have been exploring ways to address this issue for several years.

“Under this proposed new legislative program – which represents the first important step in health care reform – America’s pharmaceutical research and biotechnology companies have agreed to help close the gap in coverage. Specifically, companies will provide a 50 percent discount to most beneficiaries on brand-name medicines covered by a patient’s Part D plan when purchased in the coverage gap.

“In addition, the entire negotiated price of the Part D covered medicine purchased in the coverage gap would count toward the beneficiary’s out-of-pocket costs, thus lowering their total out-of-pocket spending. Importantly, the proposal would not require any additional paperwork on the part of the beneficiary nor would an asset test be used for eligibility.

“Since its inception, strong competition among drug plans participating in the Medicare drug benefit has led to significant savings for seniors. On average, beneficiaries are saving $1,200 annually on their medicines, and the average low-income beneficiary saves $3,900, according to the Centers for Medicare and Medicaid Services. This agreement will help to provide additional savings to even more seniors across the nation.

“Even though Medicare beneficiaries are satisfied with their prescription drug coverage – as evidenced by a recent Medicare Today survey showing overall satisfaction has grown from 78 percent at the start of the program in 2006 to 84 percent in 2009 – we have constantly explored ways to improve the benefit.

“This commitment to support legislation that will help close the coverage gap reflects our ongoing work with Congress and the Administrationto make comprehensive health care reform a reality this year.”

The Pharmaceutical Research and Manufacturers of America (PhRMA) represents the country’s leading pharmaceutical research and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. PhRMA companies are leading the way in the search for new cures. PhRMA members alone invested an estimated $50.3 billion in 2008 in discovering and developing new medicines. Industry-wide research and investment reached a record $65.2 billion in 2008.

Glaxo Chinese Joint Venture To Produce Vaccines

H. Sandra Chevalier-Batik — Tue, 09 Jun 2009 14:43:35 +0000

Glaxo Aggressively Pursues Asian Vaccine Markets

GlaxoSmithKline has aggressively pursued a vaccine-production capability in Asia with a Chinese flu shot joint venture and a new plant in Singapore to make pneumonia vaccines. The company inked an alliance with Shenzhen Neptunus to make flu vaccines for markets in China, Hong Kong and Macau; Glaxo gets a 40 percent initial stake in the JV in exchange for a contribution of cash and assets worth $34 million. Within two years, GSK plans to take a majority interest in the partnership.

Andrew Witty, CEO, GlaxoSmithKline

Meanwhile, Glaxo chief Andrew Witty went to Singapore to open its largest vaccine plant in Asia. Singapore Prime Minister Lee Hsien Loong said his city-state is “proud to be a part of this project” and said work at the $600 million, 85,000-square-meter plant could save 3 million lives per year worldwide. Over the next two years the plant will ramp up to 1,100 workers, setting up production processes and quality controls, Witty said. Glaxo expects commercial production to begin there in 2011. Lee noted that GSK and Singapore shared a longstanding and enduring relationship after it first set up a small sales office here in 1959, the year Singapore gained self-government. Since then GSK has invested S$1.5 billion and expanded its activities in Singapore into manufacturing, drug discovery and clinical research, making the city-state one of the company’s two global strategic manufacturing hubs and its regional headquarters for Asia Pacific. Lee said the republic might explore the possibility of offering the city-state to be the corporate base for global companies, both big and small. “In the past, global companies operated with just one corporate headquarters, where all their key decision-makers were based. However, Asia is now the main growth story in the world,” he said, adding that many companies were therefore looking to locate their key functions and decision makers closer to Asian markets. With more and more manufacturing and research and development taking place in the region, companies were also establishing ‘control towers’ to better manage and coordinate their research and production activities.

“Singapore’s stable and pro-business environment, excellent connectivity and competent workforce make us an ideal Asian base for these companies.“ — Singapore Prime Minister, Lee Hsien Loong

At the Singapore press conference, Witty also offered his views on the global economy: sluggish, with continued economic contraction. “This could be a relatively anemic economic backdrop for a while,” he said. “I’m not yet confident that anything is very different today than it was three months ago. I think we’re still seeing an environment very similar to the one we saw in the second half of last year.” In April, GlaxoSmithKline reported first quarter profit fell 13 per cent based on weak US pharmaceutical sales.
- see the China JV story from Reuters
- see the Bernama’s Singapore coverage
- get more from the Straits Times

GlaxoSmithKline envisions new research ties to biotechs

H. Sandra Chevalier-Batik — Wed, 03 Jun 2009 21:58:31 +0000

What do closer PHARMA ties to Educational Facilities Mean to Independent Research?

One of my favorite ePeriodicals, FIERCE BIOTECH, The BioTech Industry’s Daily Monitor featured this story by John Carroll today

GSK’s Witty envisions new research ties to biotechs

Anxious to create a more innovative environment to develop new drugs, GlaxoSmithKline CEO Andrew Witty says the pharma giant is exploring ways to link its research facilities around the world to start-up biotech companies that can collaborate on new products.

“Startups could co-locate with us and create a new type of foundation for discovery,” Witty told the International Association of Science Parks conference in Raleigh, home to one of the country’s largest research centers. And he reiterated GSK’s interest in small acquisitions and partnerships to provide a fresh jolt of new ideas for a company in bad need of good drug development programs.

Witty also underscored that the presence of large academic institutions staffed with top researchers won’t be enough to woo companies like GSK in the future. Even more important, he says, is a pro-business attitude “to make the interface between industry and academia porous.”

- check out the report from the News & Observer

Read more about: strategy, GlaxoSmithKline, Andrew Witty

The quote from Andrew Witty, GKS CEO gave me pause:

“Even more important, is a pro-business attitude to make the interface between industry and academia porous.”

Is a porous, pro-business attitude between industry and academia a good thing? Based our current experience with GKS HPV-vaccine, Cervarix, I’m thinking, perhaps not.

I read this story and followed the links and read the other articles. If you are a business-geek, chip-head like me you can see the symetry of the GSK plan. It makes business sense and takes advantage of the new IT technologies and process to streamline development processes. An old Edwards Deming grad like me throughally approves. The women’s health advocate in me is conncerned that the line between objective research and critical trial results and repoting will be blurred by the technology. GKS has not been the best corporate citizen, old school. GKS in the ‘cloud’ computing environment bare a watchful eye.

Pharma, Social Media and Public Persuasion

H. Sandra Chevalier-Batik — Fri, 22 May 2009 17:57:29 +0000

Pharma on Facebook?

My digital copy of The Scientist, Volume 23, Issue 5, just hit my in-box. The story that caught my attention was article on pg 19, by Kerry Grens, “Pharma on Facebook?”

For the full article go to The Scientist, it is good read. However the section of the piece that I though Inconvenient Women should be thinking about, is excerpted here. We need to be aware of how Pharm’s footprint in social media venues like Facebook and Twitter could effect ‘accptance’ of a product without any of that troublesome FDA disclaimer language.

“…Richman started a wiki-page of social networking sites sponsored by pharmaceutical companies, and the list is growing (www.doseofdigital.com).

Perhaps the most impressive site to date is Gardasil’s “Take a step against cervical cancer” profile on Facebook—with more than 100,000 fans. (For comparison, American Idol‘s Facebook page has about 430,000 fans.) But the big difference between the two is that “Take a step” is a one-way communicator: no comments allowed.

That is something no one in pharmaceutical marketing has quite figured out how to deal with: What if people post not just negative reviews, but adverse events, something the company is required to report to the FDA?

This puts pharmaceutical companies in an uncomfortable position, says Steve Woodruff, the president of marketing company Impactiviti, who blogged during the social networking conference. Companies could be on the wrong side of regulations if they don’t act on possible adverse event reports, “but it’s in a format where we may not be able to act on it,” he says.

Pharmaceutical companies “have to be very careful what they say, because there are agencies that will slap them with a very large ruler if the wrong things are said,” says Woodruff. The main pitfall drug companies have to avoid is allowing any misleading information to pop up on a site they sponsor.

So a pharma company could even get fined for posting information on a Twitter site that the Food and Drug Administration doesn’t approve about a product. (Still fresh in the industry’s collective memory is Eli Lilly’s $1.4 billion in fines after its sales representatives spread unapproved claims.)

Currently, the FDA has no guidelines explicitly addressing adverse event reports on networking sites like Facebook, and companies like Pfizer are not willing to take a chance that any networking activities could inadvertently step into foul territory.

Inconvenient Women everywhere need to be reviewing these sites regularly to see what Big Pharma is saying, to whom, to what effect.

For the full article go to The Scientist

How Independent Is The FDA

H. Sandra Chevalier-Batik — Tue, 19 May 2009 12:06:56 +0000

Dangerous Prescription

The following is a transcript from the Public Television series, FRONTLINE. The program, Dangerous Prescription was aired in late 2003. I’ve kept in my files for years as a source reference documents. This past week, while working on a paper with my writing partner, Leslie C. Botha, and I opened my FRONTLINE file to review the strange twists and turns of American drug approval, regulatory process. After rereading my collection of transcripts, the information and insights struck me as being applicable in our current drug safety discussion. I found reading the interviews was almost reading a historical journal. Its interesting to look at who’s opinion was spot on and what fears were justified, which proved groundless and of course what issues are still hot topics. It is a big read, take your time with it, think about it, and I hope you find it as insightful as I did.

I guess I should give the usual plug, “This transcript brought to you by, the friends and members of Public Television.”

An investigation of America’s drug safety system…more than a dozen dangerous drugs have been pulled off the market since 1997. Why were they approved in the first place.

How Independent is the FDA?

Is the FDA too cozy with the industry it regulates? Critics of the 1992 Prescription Drug User Fee Act argue that industry funding of the drug review and approval process gives pharmaceutical companies, and their lobbying arm, PhRMA, too much influence. To address these issues, in excerpts from FRONTLINE’s interviews, are Sidney Wolfe, director of Public Citizen’s Health Research Group; Steven Galson, acting director of the FDA’s Center for Drug Evaluation and Research; Raymond Woosley, vice president of the University of Arizona’s Health Sciences Center; and John Kelly, spokesman for PhRMA, the industry’s lobbying organization.

Director of Public Citizen’s Health Research Group since its founding in 1971.

How is the pharmaceutical industry making its inroads into the FDA? Where is it exerting its influence?

The pharmaceutical industry’s influence gets exerted in a number of ways. One, starting 10 years ago [with the Prescription Drug User Fee Act (PDUFA)], the influence was exerted by their directly funding, paying cash right up front, for FDA review. So in many ways, the FDA started looking upon the industry as their client, instead of the public and the public health, which should be the client.

A second way in which the industry influence occurs is by having leaders in the drug division who are spineless and gutless, and who don’t like controversy. I have heard over and over again, directly from these people, “Why can’t this be settled on a scientific and medical basis?” They don’t like to take on the very awesome forces of the drug industry and a lot of its indentured servants, so to speak, in academic medicine. So the attitude by the leaders there [is], “avoid conflict” — and avoiding conflict means doing what the industry wants.

A third way in which the industry’s influence has been allowed to grow considerably is the absence of congressional oversight. Up until 12 years ago, whenever the FDA would make a mistake — such as the series of mistakes they’ve made in the late 1990s — there would be a congressional hearing. They would have to explain to the legislative branch of the government what went wrong. They would be — properly, and in the best public health sense — on the defensive to try and explain what went wrong.

No one is there in the Congress [now]. There have been essentially one or two days of oversight hearings in 12 years, as opposed to maybe the previous 12 years with dozens and dozens of oversights. So they’re getting away with no congressional oversight.

Those are some of the reasons. And the culture at the FDA has become, “Please the industry. Avoid conflict. Look upon our role as getting out as many drugs as possible.”

What evidence is there that it’s the pharmaceutical industry influence that is changing these attitudes in the upper levels of management at the FDA, that’s overruling the scientists, that’s putting the business interests first?

The FDA is an agency of the Public Health Service. Its primary mission is to improve the public health. You have to be very cautious when — through a combination of being funded directly by the industry, as opposed to through the U.S. Treasury, and congressional influences which are pro-industry as opposed to pro-consumer — it starts moving in a way that is very favorable to the industry.

The positive opinions of the pharmaceutical industry of the FDA have never been higher than they were at least from 1997 to 2001. The last year, they’ve been complaining a little, because there’s been a smaller number of drugs approved. But one way of gauging how favorable the FDA is acting towards the pharmaceutical industry is just to ask the pharmaceutical industry what they think of the new FDA, the FDA from, let’s say, 1995-1996 through 2000-2001. They love it. They gave a former FDA commissioner an award for doing a terrific job. You would not have seen these things 10-15 years ago, when the FDA was in an appropriately vigilant and appropriately adversarial attitude with industry.

The FDA, obviously, has to work with the industry, and that’s good. But when the FDA starts getting taken over in many ways by the industry, that’s not good. In response to the questionnaire that we sent out to the physicians at the FDA, they themselves told us that, many times, they believe that industry influence was operating on the people above them, and getting their bosses to overturn some of the decisions that they had made against approving a drug.

So there are lots of sources of evidence about the fact that the pharmaceutical industry has an almost unprecedented finger or thumb on the FDA in the last few years, compared with any time in the past.

What’s the concept [of user fees]? How does it work?

For the first 86 years of FDA’s existence, from 1906-1992, all of FDA’s funding came through the U.S. Treasury. In other words, everyone — industry, people — paid their taxes, and FDA got appropriations out of the budget.

Starting in 1992, unfortunately, a law was passed that said for a large proportion of the work done by the FDA on new drug applications, the money’s going to come directly, quid pro quo, from the industry. If they want a drug reviewed, they pay directly to the FDA to have the drug reviewed.

This system has created a very unhealthy relationship — even more unhealthy than it used to be — between the industry and the FDA, where the FDA says, “We have to be nice to these people, because they are paying our bills.” It’s developed an unhealthy sort of client relationship between the government and the industry which, I think, has resulted in some drugs getting approved that shouldn’t; drugs being put on a faster track than they should have.

I think that, in general, it’s been a very bad idea. We strongly favor ending this experiment, which has had, in the 10 years that it’s been in existence, some of the worst things happen in terms of drug safety we’ve ever seen. I think that’s not the only explanation. But direct cash funding from the pharmaceutical industry to the FDA turns out to be a very bad idea.

Acting director of the FDA’s Center for Drug Evaluation and Research.

Many critics say that having industry pay for the work that’s done at the FDA puts a lot of pressure on the agency to approve drugs and please industry. What do you have to say about that?

We don’t really feel pressure to please the industry. We feel quite independent among the scientists. We have a large number of mechanisms for assuring high quality of the reports that we do to make decisions about new drugs. We just reject that we’re actually influenced by that. In fact, what’s happened over the course of the user fee activity is we’ve been able to hire a lot more people, improve the expertise of the people that we do have, provide more tools to our employees. So we think it’s really helped the review process.

What happens at the Food and Drug Administration if Congress doesn’t renew the User Fee Act? What would happen to the employees here?

I don’t think it’s really going to happen. It’s so important to the public health infrastructure of the country that we have a good strong drug review process. We just had it reauthorized for another five years. I just don’t think it’s going to happen.

In your personal opinion, wouldn’t it make more sense to have taxpayer dollars fund this rather than have industry pay for it?

Well, there are lots of hypotheticals we could go into. You know what the federal budget pressures are. So I’d try to stick to the pragmatic reality. The reality, in terms of the management of FDA, in the Center, we’re really agnostic about where the money comes from. We think we can run a high-quality independent program, regardless of the source of the resources as long as, of course, the resources aren’t linked to performance goals that are going to interfere with our independence. So far, that hasn’t been an issue at all.

Vice President for Health Sciences at the University of Arizona, he was a top candidate to become FDA commissioner in 2002.

You were under consideration to be commissioner of the Food and Drug Administration. You’ve got pretty strong ideas about making drugs safer and as beneficial as possible. … How did it go?

I was very proud that I was considered as a candidate for the Food and Drug Administration’s commissioner position. …

Unfortunately, it was a very complicated process. … As I look back over my interview and the other interviews, it was very clear that people like myself, who care about drug safety, had become too controversial. Just like Senator Kennedy didn’t want to take somebody right out of the drug industry, the drug industry didn’t want someone like myself, who was going to focus on toxicity and side effects. So it became clear that I wasn’t going to be able to meet a broad enough constituency. …

How did Secretary Thompson tell you that you couldn’t get this job? What did he say?

Secretary Thompson told me that I was a candidate, that I would be very high on his list, but that it was going to be a long process, that there were other considerations, that I might not be the final candidate, and that it would be a long time before I would know. He didn’t say that someone was going to veto me; he did say that I was a candidate that would be acceptable to him, and now he’s very proud of that. But he also said that it wasn’t just his decision.

Did he imply to you that you would not be accepted by some other powerful constituency, that it would be a problem?

Some people on his staff indicated that my stand on dietary supplements and especially ephedra-containing supplements — I’ve asked the FDA to ban these, because I think they are killing people and they must be regulated as drugs — I think his staff told me that that had really alienated a very powerful part of the dietary supplement industry.

It became clear that anyone who had focused on drug safety couldn’t make it, just like people who had come right out of industry couldn’t make it. Too far on the extremes to be acceptable.

To me, the greatest sadness is that people who care about drug safety and food safety to the level that they get involved and they try to make a difference can’t be acceptable to regulate the agency. I think that’s one of the main criteria that should be used. Of course the regulators have to serve, but they also have to regulate and they have to protect. To me, protection is first; serve has to be second. You’ve got to take risks. You can’t just be risk-averse and unwilling, because people need medications and they need access to foods, so it’s the ability to balance risk and benefit. To work in drug development and focus on drug safety, you become identified with the risk and not the benefit.

Is the balance of the FDA out of whack, in your opinion?

I think the FDA is so grossly underfunded for its mission that it is out of balance because of user fees. User fees enable the agency to hire people to work for the industry. The other budget has been so limited and so cut — the other budget being that which is there for safety — the number of people hired at the agency to protect, to analyze data and drug safety, is criminal. The number of people required to study 3,000 drugs that are on the market is far more than the 17 or 20 — however many they have now. The teams that are needed to do drug safety are infinitely more than what they’ve got right now. We don’t have a safety system in this country.

Why is the safety part resisted so adamantly? How do you explain it?

The budgets of the FDA are determined by lobbyists who call for money to be spent in certain ways. The user fee is negotiated to be spent on reviewers. Until recently, none of the money that was sent by the pharmaceutical industry for user fees could be used for drug safety. Now that’s changing — not to the rate I’d like to see it. Some of the money can now be spent for drug safety, but that was impossible until recently. It’s only because many of us have screamed that that has to change has it changed. …

What’s the lobbying in terms of safety?

Nothing. They’re not lobbying for safety. … The pharmaceutical industry doesn’t lobby for safety. They lobby for rapid review, rapid access to the marketplace. They haven’t lobbied for drug safety; no one has. There are groups, consumer groups, that have spoken out, but not with a uniform voice. Large constituencies haven’t joined together to say, “Stop the harm.” When the papers came out from the Institute of Medicine talking about medical errors and medical harm, I thought surely there would be action taken and the agency would be given money to increase its safety net. But it hasn’t happened. There’s a lot of lobbying for helping the agency serve. … No lobbying [is] being done to help it get its safety mission accomplished.

Spokesman for the Pharmaceutical Research and Manufacturers of America (PhRMA), the industry’s lobbying organization.

What is PDUFA, or the User Fee Act? Where did it come from?

The Prescription Drug User Fee Act was established over a decade ago [in 1992] to provide a way to help improve the availability of resources at the Food and Drug Administration to review pharmaceuticals. It’s a process which has worked very, very well in increasing the scientific expertise within the agency to allow timely, effective, and thorough review of prescription drugs.

This is something that was largely pushed by the pharmaceutical industry. Give us some history from the industry’s perspective.

The pharmaceutical industry is remarkably productive. We develop a number of new medicines every year. Part of the challenge that we’ve found was occurring a number of years ago — that the FDA didn’t have the resources to do the reviews in a timely and effective way. So PDUFA was a way to help improve the resources available to the Food and Drug Administration so they could review pharmaceuticals.

This act has been very effective. It has improved the efficiency of the review process. It has not changed the standards or the review process, so the drugs that are ultimately approved by the Food and Drug Administration are determined by the FDA to be safe and effective. So PDUFA has worked very, very well in helping to improve timely access to beneficial medicines. …

So are your member companies, the pharmaceutical companies, happy?

The pharmaceutical industry has been pleased with PDUFA and has been very supportive, because what it has done is to improve the efficiency of the review process. It’s in the pharmaceutical industry’s interest and in the public’s interest to have that review process as thorough and effective as it can be. I think that we have made tremendous progress during the last decade in improving the review process. In fact, we expect that the process will continue to improve, and we welcome that.

Of course, there are critics of that whole system. There are lots of people who say, “Congress should do something about this. And why has Congress left it to industry?” How do you respond to that?

Congress decided how to fund the FDA. Congress reviewed and passed PDUFA — not once, not twice, but three times. Congress has decided this is the way it wants to fund the activities of the FDA. Industry has been supportive, because what this has done has been to allow the FDA to complete the review process in a timely way, and ultimately to allow the public to have access to beneficial medicines. …

What the pharmaceutical industry is interested in is having a strong FDA, with effective reviewers who can complete reviews in a timely way to help assess the benefits and the risk of pharmaceuticals, so that medicines that work and that are safe can be available to the public. …

I’ve heard from a lot of people inside the Food and Drug Administration — some people who’ve quit, some people who are still there and would like to talk, but their jobs are threatened. They say that having the industry fund the Food and Drug Administration [has been] for the worst, that there’s an atmosphere there [that says, "Please the industry, approve as many drugs as possible"]. What do you say to these people? I’ve heard it from dozens of people, literally. … What do you say to them?

The Congress has repeatedly looked at how it wants to fund the FDA. So once, twice, and again, last year, the Congress decided that the best way to fund the FDA was to look to the pharmaceutical industry to provide a portion of the funds to help support review. That’s the decision of the Congress. The pharmaceutical industry has contributed the funds to support the review, because we think that has been an effective approach. We also think that it’s been a way of helping to advance science.

We have learned over the course of this time a tremendous amount about how to monitor risk, how to assess risk. We’ve developed a wide variety of new tools to help monitor the safety and effectiveness of pharmaceuticals. The system’s been working. There is also a very strong commitment on the part of the FDA, as well as on the pharmaceutical industry, to improve the system. So we look forward to the continued progress in the system that we have in place today.

Politics, Profits and Pharma

H. Sandra Chevalier-Batik — Mon, 18 May 2009 17:37:28 +0000

The following is a transcript from the Public Television series, FRONTLINE. The program, Politics, Profits and Pharma was aired on November 13, 2003. I’ve kept in my files for years as a source reference document. This past week, while working on a paper with my writing partner, Leslie C. Botha, and I opened my FRONTLINE file to review the strage twists and turns of American drug approval, regulatory process. After rereading the transcript, the information and insights struck me as being applicable in our current Gardasil discusion. It is a big read, take your time with it, think about it, and I hope you find it as insightful as I did.

I guess I should through in the usual plug, “This transcript brought to you by, the friends and members of Public Television.”

The pharmaceutical industry is one of the most powerful interest groups in Washington — one that has rarely shied away from wielding its influence with Congress and the FDA. But are the industry’s lobbying efforts always good for business?

In 1906, when Congress was about to pass the first federal law to protect food and drug safety, a trade group representing companies that made medicines (or what passed for them back then) warned darkly: “Such a law would practically destroy the sale of proprietary remedies in the United States.”

The relationship between drug manufacturers and those who would regulate them had not improved much by the 1930s, when Congress was on the verge of passing the first law requiring drug makers to demonstrate that their products were safe before selling them. The bill, industry groups wrote in a letter, “will put thousands of men and women out of work. It will close dozens of manufacturing plants and hundreds of stores. … It will help none.” And in the 1960s, when Congress was about to pass a law requiring drug companies to demonstrate that drugs were not merely safe but were effective as well, the pharmaceutical industry once again warned of dire consequences — specifically, that drug prices would rise, innovation would slow, and millions would lose their jobs.

As we all now know, none of these dreadful consequences ever materialized. On the contrary, as Philip Hilts recounts in his sweeping history of the Food and Drug Administration, Protecting America’s Health (2003), the American pharmaceutical industry not only survived the efforts at regulation during the 20th century, it actually thrived as a result of them. Every time the government demanded something more of the drug industry — every time it raised its standards for safety or efficacy — the industry responded by making better products that enjoyed more consumer confidence, which ultimately meant not just better medicines for patients but bigger profits for the drug companies. “The regulations and the government shepherding of the drug business did what the free market failed for at least sixty years to do,” Hilts wrote of the 1938 law, although he might well have been writing about any one of the major drug safety acts during the last century.

“It weeded out the brutal, the stupid, and the needless that prevented the pharmaceutical industry from becoming a great engine of discovery and sales.”

It’s worth keeping that in mind when looking at some of the more recent battles pitting the drug industry against its regulators. Although drug company executives and representatives speak in genial tones when they talk about the FDA publicly, they have also lobbied to make the agency more docile and business-friendly. Because the pharmaceutical industry is one of Washington’s most powerful interest groups, many of these efforts have succeeded. But given the history of pharmaceuticals in America, it’s fair to ask whether, in the long run, these successes will help the drug industry or hurt it — by undermining the outside watchdog that guarantees the credibility essential to its financial survival.

Probably the single most important shift in the FDA of the last decade has been the change in how the agency approves new drugs — or, more precisely, how quickly it approves new drugs. In the late 1980s, the pressure to speed up drug approvals was rising. And it wasn’t just the drug makers complaining. It was doctors and patients who were agitating, too, over everything from why the FDA hadn’t approved the chicken pox vaccine (even though European nations had approved its use for years) to why it wasn’t moving faster on potentially life-saving AIDS treatments — a grievance that famously led to mass protests outside FDA headquarters in Rockville, Maryland. These public displays of disaffection, combined with behind-the-scenes lobbying by pharmaceutical manufacturers and their trade groups, finally produced the Prescription Drug User Fee Act (PDUFA) of 1992.

Under the terms of PDUFA, the drug industry agreed to help finance the approval process — through “user fees” accompanying each new drug application — in exchange for an FDA promise to speed up its deliberations. Widely considered one of the most significant pieces of legislation in FDA history, it would effect a remarkable transformation: In 1992, it had been taking the FDA an average of 30 months to approve a new drug. By 1996, the agency had cut the time nearly in half, to 16 months, prompting outgoing commissioner David Kessler to announce (accurately) that “the U.S. is now a world leader in drug review.”

Naturally, not everybody was so enthusiastic about this shift. Consumer advocates and other watchdogs had never been entirely comfortable with the user-fee arrangement, since it seemed to make the FDA financially beholden to the very industry it is supposed to regulate. More important, critics feared that the haste to approve drugs would let more unsafe drugs get into the market — a fear that did not dissipate in subsequent years. A 2002 report by the General Accounting Office showed that the rate of drug recalls had increased in the years since PDUFA’s passage. Among the GAO’s recommendations were that the FDA do more to monitor drugs even after they’ve been approved — a sensible idea given that, according to one study in the Journal of the American Medical Association, more than half of the dangerous side effects of drugs are detected only after they’ve been on the market for seven years or more.

But the drug industry sees things a little differently, disputing, among other things, the results of that GAO study. If they have a complaint about the drug approval process, it’s precisely the opposite one: that the FDA is still too slow. By 2002, the average approval time for a standard application had risen to 19 months, up from a low of 13 months in 1998, prompting Pfizer’s CEO, Henry McKinnell, to complain to Business Week that “The FDA has become more risk-averse.” And while the approval time was still far less than what it was before PDUFA’s enactment, drug industry executives began calling attention to another figure: the average “development time” for a drug, including the time invested before a company even applies formally for approval. According to studies by Tufts University researchers, it now takes more than seven years to develop a new drug — up from six a decade ago. A major reason for this increase, say the drug makers, is that the FDA demands too much scientific information about a new drug before granting approval — far more information, the drug makers say, than is necessary to guarantee efficacy and safety.

Earlier this year, these complaints produced at least a rhetorical response. Upon taking office in 2003, new FDA commissioner Mark McClellan pledged to reduce the average drug approval time by 10 percent. As a practical matter, though, even industry allies concede there’s only so much more the FDA can do to compress a process that’s already relatively compressed — particularly since the types of drugs companies now produce, and the types of diseases they seek to treat, are inherently more complicated than they were a decade ago. As Wayne Pines, a former FDA official who now consults for the pharmaceutical industry, explains, “Drugs being developed now are much harder to assess than previous ones. Measuring an antibiotic, that’s easy: it either works or it doesn’t. Now we’re treating heart disease, producing quality-of-life drugs. It’s much harder to assess. I don’t think the standards have changed so much as the drugs have changed.”

Precisely because the prospects for further accelerating the approval process seem slim, the industry in the last few years has expended considerable lobbying efforts on other issues. Many of these efforts have taken place through PhRMA, Pharmaceutical Research and Manufacturers of America, one of Washington’s most powerful trade groups. PhRMA is a well-financed, well-staffed operation: according to a report by Public Citizen, the liberal watchdog group, PhRMA alone employed 50 lobbyists in 2001. (The drug industry as a whole used more than 600 lobbyists that year, the report said.) But the reason drug lobbyists have had so much clout is that the pharmaceutical industry has spent a great deal of money financing political campaigns, devoting dramatically greater sums each year. According to the Center for Responsive Politics, the pharmaceutical industry spent $22 million on campaign contributions in 2002 — or more than nine times what it did in 1990. Given that the industry spends untold millions more on advertising and other forms of issue-oriented public relations, it’s no wonder Illinois Senator Dick Durbin, a Democrat, recently declared that PhRMA “has a death grip on Congress.”

That may be overstated. But one case study that demonstrates the industry’s power is the issue of so-called “pediatric exclusivity.”

Prior to the 1990s, drug companies rarely tested their products on children, in part because testing on children is more complicated than testing on adults (for ethical reasons) and in part because it was just plain expensive. But by the 1990s, with studies showing that some 80 percent of all children’s medications hadn’t actually undergone specific pediatric testing, the pressure to run more clinical trials for children had become almost irresistible. So rather than fight the inevitable, the industry settled for a compromise: it agreed to drop its objections as long as Congress agreed to compensate the companies. Specifically, if a drug company voluntarily tested its product on children, the government promised to extend the company’s patent on that drug by six months.

The law succeeded, in the sense that it increased pediatric testing. But the reformers who’d pushed for the measure quickly came to rue the cost. Pediatric testing may be more expensive than regular adult testing, but the price pales in comparison to the amount of money a drug company makes from extended patent protection for an extra half-year. (This is particularly true since the exclusivity applies to every form of the drug, not just the one tested on kids.) According to the FDA’s calculations, pediatric exclusivity will bring brand-name drug makers a net windfall of about $30 billion over 10 years — $14 billion of it out of the pockets of consumers paying higher prices than they would have otherwise. (Carl Seiden, a well-regarded industry analyst with JP Morgan Chase, has estimated that the six-month extension on Prozac alone brought Eli Lilly an extra $1 billion in sales, $700 million of it pure profit.)

Mindful of these figures, and the fact that millions of Americans have been struggling to pay for their expensive prescription drugs (see FRONTLINE’s recent report “The Other Drug War”), industry critics in Congress such as Rep. Henry Waxman, a Democrat from California, tried in 2001 to renegotiate the arrangement. Under Waxman’s proposal, instead of extending patents, the government would simply pay industry twice the cost of actually running the pediatric studies. But the drug lobby would have nothing of it. Warning that cuts in the financial incentive would leave the industry with little choice but to abandon pediatric testing, drug makers lobbied Congress to preserve the arrangement unaltered. It even hired two former congressional staffers, who had worked on the committees with jurisdiction over the legislation, to help make the case. The industry prevailed, and the law was renewed with no substantial changes.

A case where the industry has more clearly fought the FDA itself — and largely won — is the area of “off-label” promotion and advertising. Few mandates are more fundamental to the FDA’s mission than its duty to police what drug companies say about their products. (As Hilts documents in his book, it was misleading claims about medications that sparked the very first attempts to regulate drugs back in the 19th century.) And in theory, anyway, the 1962 drug safety act very explicitly prohibits manufacturers from promoting drugs for uses other than those specifically sanctioned by the FDA during the approval process. The reason? The architects of the 1962 law suspected that in the absence of such rules, drug companies would make unsubstantiated boasts just to enhance their sales, potentially sacrificing safety. “The initial claim would tend to be quite limited,” supporters of the 1962 bill said at the time. “Thereafter, the sky would be the limit. … Extreme claims of any kind could be made.”

The drug industry has long protested these regulations, saying that requiring such extensive proof has led — as Pfizer attorneys recently put it — “to a regime where manufacturers are precluded from using advertising for its intended purpose.” And the industry position has a certain logic to it. After all, a drug that treats indoor allergies like dust probably works well against outdoor allergies like pollens, too. Why force the companies to stage a whole new set of clinical trials, then force them to wait — losing valuable patent time — while the FDA takes a year or more to review the data? As long as a manufacturer has demonstrated that a drug is safe, the argument goes, shouldn’t it be free to promote the drug however it wants, and allow physicians to determine — based on their own reading of any available studies — whether it’s appropriate in certain cases? Physicians already have that freedom, and use it all the time, particularly in specialties like psychiatry where the boundaries between different disorders are blurry in the first place.

Unfortunately, doctors rarely have the time (or, in many cases, the desire) to keep up with the latest clinical data. As such, they are basically at the mercy of the drug companies, some of whom have promoted their drugs beyond approved uses, despite safety concerns.

During the mid-1990s, for example, executives at Parke-Davis, a Warner-Lambert subsidiary at the time, allegedly marketed an epilepsy drug called Neurontin for such unapproved uses as migraines, social phobia, and manic-depressive disorder. Their methods: staging continuing medical education classes noting these uses, financing speeches by doctors who would promote off-label treatments, even hiring public relations firms to help physicians write up journal articles touting the medication’s alternative uses. These techniques came to light after a former Warner-Lambert scientist named David Franklin came forward as a whistleblower, prompting a federal investigation that uncovered internal memos documenting the campaign. In an interview with The New York Times, Franklin said he was told to exaggerate the results of favorable studies and to suppress evidence contradicting the company’s off-label claims. “We were truly experimenting on patients, which put them at risk,” Franklin said. “I was involved in this, trained and asked to deceive physicians and take advantage of their trust, and I’m embarrassed by that.” (Franklin has brought a whistleblower lawsuit against Parke-Davis and its new parent company, Pfizer. But because Pfizer acquired Parke-Davis well after the alleged conduct occurred, its spokesman declined to comment on the case — except to say that Pfizer itself does not promote off-label usage.)

This doesn’t appear to be an isolated incident, or the most egregious one. During the 90s, Wyeth promoted the drug Cordarone for “early use” against heart disease — even though the FDA had approved it only as a last-resort medication. At the same time, according to an investigative story by Lee Scheier in the Chicago Tribune, Wyeth failed to warn U.S. physicians and consumers about some of the drug’s potential side effects on eyesight, even as it was printing such warnings on drugs that were being sold in Canada. Years later, the company — already in legal trouble over the Fen Phen diet drugs — ended up paying more than $30 million to two men who developed permanent blindness after taking the drug (although the company has denied any wrongdoing, and says their drug didn’t cause the eye problems). A recent series by Knight-Ridder reporters Chris Adams and Alison Young documents several other incidents of off-label promotion. For example, the FDA twice warned Bayer that it was improperly promoting the antibiotic Avelox for unapproved uses — although Bayer has denied doing so. Back when the drug was first approved by the FDA, one reviewer speculated that “This is exactly the kind of place that you get into trouble. … I am absolutely convinced that the drug will be used differently once it’s marketed frequently.”

Despite publicity over episodes like these, efforts by the FDA to clamp down on off-label and other instances of inappropriate advertising have been pretty ineffective. To some extent, the problem is largely a practical one, since so many of the promotions take place beneath the FDA’s radar. “In any given year, you have 400,000 dinner meetings with doctors,” says industry consultant Wayne Pines. “Who’s regulating that? Nobody can.” But even in those cases where the FDA has evidence of wrongdoing, it doesn’t seem to be pursuing them with the relish it once did. Last fall, Waxman’s office wrote a letter to the FDA documenting a precipitous drop in so-called “enforcement actions” against companies that use misleading advertising. From 1999 to 2001, the FDA had issued one warning letter for every 2.8 complaints of improper or false advertising; in the first few months of 2002, the rate fell to one letter for every 13.5 complaints.

One likely reason for the slow-down is that all such letters must now be reviewed by the FDA’s chief counsel, Daniel Troy. Before coming to the FDA in 2001, Troy was a lawyer representing the pharmaceutical industry who spent much of his time filing lawsuits challenging FDA advertising regulations. Since his appointment, he has steered the FDA in a more cautious direction. For example, as The New York Times reported this summer, it took 78 days for Troy’s office to approve a letter warning Tap Pharmaceuticals to withdraw ads making misleading claims about the heartburn drug Prevacid — this despite an admonishment, just months before, from government auditors that the FDA was taking far too long to follow up on complaints. (Troy says he simply wants to avoid legal challenges that might undermine his agency’s authority. As he told The American Lawyer, “The public health cannot abide an FDA that lacks credibility in court.”)

Naturally, not everybody was so enthusiastic about this shift. Consumer advocates and other watchdogs had never been entirely comfortable with the user-fee arrangement, since it seemed to make the FDA financially beholden to the very industry it is supposed to regulate. More important, critics feared that the haste to approve drugs would let more unsafe drugs get into the market — a fear that did not dissipate in subsequent years. A 2002 report by the General Accounting Office showed that the rate of drug recalls had increased in the years since PDUFA’s passage. Among the GAO’s recommendations were that the FDA do more to monitor drugs even after they’ve been approved — a sensible idea given that, according to one study in the Journal of the American Medical Association, more than half of the dangerous side effects of drugs are detected only after they’ve been on the market for seven years or more.

• • •

That may be overstated. But one case study that demonstrates the industry’s power is the issue of so-called “pediatric exclusivity.”

• • •

It’s easy to see why the pharmaceutical industry might want a freer hand to advertise its wares — and why, in the short run, it might even make more money that way. But in the long run, allowing the industry to make misleading claims about its products could also serve to undermine its credibility with consumers. The same goes for efforts to speed up the drug approval process. Getting medicines to market faster obviously helps the drug industry’s bottom line. But if, as consumer advocates charge, it ends up putting more dangerous products on the market, it is the industry’s own revenues that will fall as a result of falling confidence (and rising litigation costs). Even the extension of pediatric exclusivity could come back to bite the drug industry. One can argue that the more quick-and-easy opportunities drug companies have to increase profits from today’s products, the less incentive they will have to invest in research to generate tomorrow’s blockbusters.

That might all seem rather hypothetical — until you consider just how the drug industry has been doing lately. On Oct. 23, three major drug companies published disappointing financial reports. Merck said it wasn’t going to meet its profit projections — and would be eliminating more than 4,000 jobs — partly because it had no promising new drugs in development. Schering-Plough and Wyeth had to revise their own profit forecasts downward, in each case citing (among other reasons) millions of dollars spent defending themselves in lawsuits alleging that they made false claims about their products or put unsafe products on the market. Wall Street responded accordingly, with the Standard and Poors’ pharmaceutical index falling to 3 percent below its level at the beginning of the year. (By contrast, the broader S&P 500 index was up 17 percent by that date.) Assuming the next two months bring no improvement — and nobody seems to think it will — 2003 will go down as the third consecutive year of declining stock prices for the drug industry.

Lack of innovation. Misleading claims about products. Potentially unsafe drugs on the market. These were exactly the sorts of conditions that led the federal government to create the FDA and then strengthen it over the years. The pharmaceutical industry should keep that in mind the next time it tries to stop the agency from meddling in its affairs.

Jonathan Cohn, a senior editor at The New Republic and a Media Fellow at The Kaiser Family Foundation, is writing a book about the U.S. health care system.

Inside a Contract Research Organization (CRO)

H. Sandra Chevalier-Batik — Mon, 18 May 2009 16:18:44 +0000

Health Decisions Celebrates 20 Years of Adaptive Clinical Research

This past week we have addressed the issue of CROs (Contract Research Organizations) and how the financial relationship with Big Pharma could possible effect aspects of drug trials. The Durham-based CRO discussed below believes the concept of “agile clinical research,” an adaptive system that allows mid-trial improvements to both operations and design that can help sponsors get drugs and diagnostics to market faster and cheaper. I found the information in the article in “eCliniqua.” It is an interesting look at the thought process and corporate culture at one of the most successful CROs in the country.

In building a company of some 150 employees over the past two decades, Health Decisions founder and CEO Michael Rosenberg has presumably done something right. But he maintains the industry is still doing a lot wrong. “The drug industry’s remarkable success has made it reluctant to change, but some changes are long overdue,” says Rosenberg .

The Durham, N.C.-based CRO espouses the concept of “agile clinical research,” an adaptive system that allows mid-trial improvements to both operations and design that can help sponsors get drugs and diagnostics to market faster and cheaper. Rosenberg says his firm’s success is predicated on technology as a platform. “You can’t manage effectively without timely information, and you can’t get that information without the kind of technology we use. Clinical research has not taken advantage of technologies that other industries have been using for years. When you look at the economic difficulties the industry is having, I think that technology as an enabler is way, way overdue,” says Rosenberg.

“The drug industry tries to manage complex, clinical operations without timely information because it doesn’t collect and process information fast enough,” Rosenberg sighs. “The industry hasn’t seen a need to manage trials based on near-real-time information.” But that provides “a great opportunity to improve efficiency,” says Rosenberg. “Efficiency is going to determine who leads the industry into the next era, not megamergers and off shoring.”

‘Agile’ clinical research encompasses design adaptations, operational adaptations, and underlying technology that make continuous adaptation possible—changing in response to changing information. (That philosophy will be detailed in Resenberg’s forthcoming book—Adaptive Research the Agile Way: Optimizing Efficiency in Clinical Development—to be published by Wiley later this year.)

Rosenberg recalls a recent interview with a big pharma executive who admitted his firm was so poor at early development that it was shifting strategy and buying drugs developed by other companies. “I thought, well, that’s a very striking statement. Outsourcing early drug development doesn’t reduce risks—it delays risks and raises the stakes. It makes more sense to develop your own drugs, but learn how to do it more efficiently. It’s pretty sad when a major company thinks it’s incapable of becoming efficient.”

Rosenberg believes fast, accurate data capture is essential for running clinical studies efficiently. Web-based EDC is not up to the task, Rosenberg says. Health Decisions placed its first remote EDC system more than 15 years ago, but there were problems, particularly around data entry. “If you look today at the problems in web-based EDC, it’s exactly the same problem. Somebody’s got to sit down at a keyboard and enter data. Until they have the time and inclination to do that tiresome chore, data sits around in batches. That delays finding out about problems. Meanwhile, the same problems recur again and again.” Moreover, web-based EDC systems don’t collect performance metrics. “You need more than the patient data—you need timely information on the status of all key operations,” he says.

A major reason the industry is so expensive and error prone is that it recruits about 85% of studies late. Why is that? “The problem with web EDC is, it doesn’t tell you which recruitment strategy is working and which isn’t, or what’s responsible for screen failures, or how different inclusion/exclusion criteria are affecting recruitment. There’s no quick way to find out if I’m spending money well on recruitment strategies. Our system tracks information that lets you manage recruitment efficiently.”

Waste Not
“Typical clinical studies waste a tremendous amount of time and money,” Rosenberg continues. “About 1/3 study budgets are spent redoing stuff that wasn’t done right the first time.” He says the clearest indicator of waste in the industry is the query rate. When a site submits data, Health Decisions runs the data through a validation engine. Sometimes, the site receives a note saying, we didn’t get a response for this question, could they clarify what it is? Queries are necessary to ensure accuracy, Rosenberg says, but that does not mean study managers should be complacent.

“The query ratio for web EDC systems is usually 5-7 queries per 100 fields. We looked at this and said, we need to make it easier for sites to enter data. But once you’ve submitted the data, we want to identify the problems right away… You don’t want sites to make the same inadvertent or dumb mistakes while waiting for queries to come back. You don’t want to find out six months later that ambiguous instructions for the CRF were causing the errors.”

Rosenberg sees parallels between the state of clinical studies and the downfall of the U.S. car industry 50 years ago, when assembly line workers counted on fixing mistakes at the end of the line. “Toyota stopped the assembly line and fixed problems immediately, diagnosed the cause, and fixed that, too,” says Rosenberg. “The institutionalized query system with all its delays is like the rework area in an obsolete car factory. You expect queries, and clinical studies focus on processing queries, but there’s not much urgency about it. Queries often get resolved when regularly scheduled site visits roll around, not immediately. Meanwhile, errors and queries proliferate.”

Rosenberg says the most important metric is, what’s the interval between when a data point is generated and when the CRO gains access to it in house? “In typical studies, there’s a very long feedback loop. We know from other industries, if you want people to decrease their frequency of errors, you have to provide quick feedback.” This is where machine-read entry and the digital pen (a Health Decisions hallmark) come in handy.

Digital Penmanship
There are usually 1-2 digital pens per site. The digital pen writes on a piece of special paper that has a very fine grid pattern, which orients the pen as to which form it is and where it is on the form. Once the pen is docked, the data are transmitted to Health Decisions, much like a PDF. Upon arrival, it is machine read into the system, where it can undergo immediate validation. “When I’ve written your name, I dock the pen,” says Rosenberg. “If I’m collecting data in Croatia, and its 4 p.m. there and somebody’s interviewing a patient, I can have this information on your desktop in digested form before the patient walks out the door.” The system is poised to validate information, issue queries, and update operational performance metrics as soon as the data comes in.

If the system works, one expects to see a lower query rate, and that’s exactly what Rosenberg delivers. The query rate is 1 per 100 fields, even lower in bigger studies. According to a commentary last year in Science, each query costs about $350. “That’s pretty reasonable when you consider all the costs,” says Rosenberg. But “take that $350 and multiply by 10,000 queries over the life of a study…. You’re wasting a couple of million dollars.”

He adds: “We can tell where our recruitment dollars are best spent. We know why patients come in… If someone doesn’t show up for an appointment, we jump on that.” By contrast, he says, “Phase Forward and Medidata grew up around the data technology nerds and they’re not focused around the users of the system… I think the technology world that we work in misses 90% of the important stuff that’s helpful to shortening timelines and reducing costs.” A new release of Health Decisions includes web 2.0 capabilities to enhance collaboration between sites.

Just as Apple puts things together by thinking about the user and making their life easy, Rosenberg says his priority is “making the user’s life dead easy. You get fewer data entry errors and delays if you make data entry really easy—as easy as writing with an ordinary pen.” Could he be considered the Steve Jobs of the clinical world, I ask? “That’s probably a stretch,” he laughs.

The Health Decisions central system integrates all the components in a clinical study: data collection, adaptive randomization, site payments, administrative functions, and a reporting suite. “We’ve been using dedicated study websites for reporting and coordinating for 7-10 years,” says Rosenberg. “I assumed everyone was doing this. But almost nobody else does that. From a technology standpoint, this is a no brainer. It’s the quickest, easiest, most efficient way to distribute information.”

David and Goliath
Health Decisions recently finished a sizeable study of 4,000 patients for a start-up company that was battling a big pharma. “This was a David v. Goliath story,” says Rosenberg, who says the CEO of his client said: “You did for $7 million what Roche failed to do for $20 million.” “We catapulted them ahead of Roche,” says Rosenberg. “This [diagnostic] product was just approved by the FDA.”
Health Decisions was able to do everything quickly: recruitment, data entry, and study turnaround. “The FDA audited this study, and normally they’d come out to the CRO. They were comfortable enough with the pen that we could provide everything online. I believe this sets a new benchmark. We did this without a single 483 [FDA notice of a discrepancy].”

At a recent CHI conference, one IT staffer from a pharma company was quoted as saying: “All EDC vendors lie… None can do adaptive trials.” Rosenberg begs to differ. Almost every study Health Decisions does is adaptive. “Some types of EDC can do adaptive studies, but they have to be able to collect, transmit, and validate information quickly, and to generate timely metrics on study progress and operational efficiency… The digital pen and our systems make that routine.”

Rosenberg says his company is “ a little unusual for a CRO. We work with a lot of companies to consult on the design. Most companies are just beginning to dip their toe in this stuff.