The user fee proposal is one of three such agreements that the agency is submitting to Congress for approval by lawmakers. The agreements would each charge drug manufacturers application fees for reviewing traditional drugs, generic drugs and a new class of generic biotech drugs, respectively.

The FDA has used industry fees to hire extra staff to review regular prescription drugs since 1992. One of the proposals unveiled Friday extends that approach to generic drugs, which have long had slower review times.

Whereas most new drugs are reviewed in 10 months, the typical review time for a generic drug is 30 months. The FDA has a backlog of more than 2,000 generic drug applications awaiting review, according to the Generic Pharmaceutical Association.

The FDA proposes collecting $299 million in fees annually to hire additional generic drug reviewers starting in fiscal year 2013. That figure would come from an estimated 750 generic drug applications per year as well as other fees, including the inspection of foreign drug manufacturing sites. In return for these fees, the FDA will aim to review 90 percent of generic drug applications within 10 months.

“These agreements are important because they are a substantial resource that lets the agency carry out its mission of protecting patients and ensuring important products come to market in a timely way,” said Allan Coukell, director of the Pew Charitable Trusts’ health advocacy group. “For the first time we will also have funding directed at increasing FDA’s inspection of foreign manufacturing facilities.”

Another first-of-a-kind agreement would charge companies for the review of generic versions of biotech drugs, which are complex medicines that often contain proteins and living microorganisms.

Up until 2010, the FDA did not have authority to approve knock-off versions of biotech drugs, or biosimilars, which are produced using far more complicated manufacturing processes than traditional chemical drugs. But the Obama administration’s health reform law signed into law in March 2010 instructed the FDA to begin reviewing and approving biosimilars. The FDA is still drafting instructions on how companies should submit applications for biosimilars.

The FDA also sent Congress its proposal for the traditional prescription drug user fee program, which is expected to raise more than $712.8 million in fees annually over five years. Like the other agreements, the deal must be approved and drafted into law by Congress before Oct 1, 2012, to be in place for the government’s next fiscal year.

Lawmakers already have granted three 5-year extensions to the Prescription Drug User Fee Act, which has allowed the FDA to hire hundreds of additional scientists in return for meeting certain performance goals. Under the latest version of the agreement, the FDA would be tasked with providing more meetings and updates to companies that have submitted first-of-a-kind drugs for review.

Separate but similar talks between the FDA and medical device makers are dragging out over a number of disagreements. Those companies have made shorter review times a priority, though the FDA says that goal will require significantly more funding, according to minutes from closed-door meetings between regulators and company executives.

Copyright 2012 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

“Smoking is the leading cause of preventable death in the United States,” said Leighton Ku, Ph.D., professor of Health Policy at the GW School of Public Health and Health Services, who led the research project. “Millions of low-income smokers in the U.S. are insured by Medicaid. In 2004, smoking-related Medicaid expenditures for all states combined was $22 billion, which represented 11 percent of all Medicaid spending.
Investments in comprehensive tobacco cessation services in Medicaid can improve the health of patients, as well as save money for states and the federal government.”

The research focused on estimating the costs of tobacco cessation programs compared to the savings that Medicaid will realize due to fewer inpatient hospital visits for heart attacks and related cardiovascular conditions. Researchers used data gathered from the 2002-2008 Medical Expenditure Survey and the Behavioral Risk Factor Surveillance Surveys to estimate the cost of hospital inpatient admissions for smokers covered by Medicaid. A smoking cessation program in Massachusetts, which offered a wide range of smoking cessation medications, as well as individual and group counseling for Medicaid recipients, proved to be successful and was estimated to have saved an average of $388 per user per year.

The Patient Protection and Affordable Care Act (PPACA) will add millions of new Medicaid recipients in 2014 and tobacco cessation services in Medicaid could soon be offered to a much larger share of the low-income smoking population. Researchers concluded that despite the Medicaid budgetary shortfalls faced by state and federal governments, a comprehensive tobacco cessation program for Medicaid enrollees is an evidence-based policy strategy which should improve public health and reduce health care expenditures.

The full article can be found at: http://dx.plos.org/10.1371/journal.pone.0029665

About the George Washington University School of Public Health and Health Services:
Established in July 1997, the School of Public Health and Health Services brought together three longstanding university programs in the schools of medicine, business, and education that we have since expanded substantially. Today, more than 1,100 students from nearly every U.S. state and more than 40 nations pursue undergraduate, graduate, and doctoral-level degrees in public health. Our student body is one of the most ethnically diverse among the nation’s private schools of public health. http://sphhs.gwumc.edu/

About Partnership for Prevention:
Partnership for Prevention was founded in 1991 by leaders dedicated to making disease prevention and health promotion national priorities and America a healthier nation. ActionToQuit, Partnership’s tobacco control initiative, urges all sectors – health care systems, employers, insurers, government agencies, quitlines, and policymakers – to work together to develop and promote sound tobacco control policies. www.prevent.org

Life Technologies Corp., a Carlsbad, Calif., genomics company, plans to introduce Tuesday a machine it says will be able to map an individual’s entire genetic makeup for $1,000 by the end of this year. Moreover, the machine and accompanying microchip technology, both developed by the company’s Ion Torrent unit, will deliver the information in a day, the company says.

 If Life Technologies delivers on the claim, it would likely make the company the first among a group of rivals racing to produce a $1,000 gene map. The current cheapest sequencing costs about $3,000 and takes a week.

The goal, triggered in part by an initiative launched by the U.S. government’s National Human Genome Research Institute in 2004, already has resulted in a dramatic cost reduction in sequencing all three billion units of DNA, known as base-pairs, that make up the human genetic code.

Scientists say that breaking the $1,000 barrier—roughly the price of an MRI test—will accelerate an already fast-moving transformation in genetic discovery and drug development.  Some experts believe a person’s genetic code eventually will be used routinely to guide prevention and treatment of illnesses throughout life.

Drug companies increasingly are identifying gene variants that they can target with drugs. And geneticists are identifying more and more diseases that result from a mutation in just one gene.

The hope is that mapping variations in the entire human genome can speed up or improve disease diagnosis and aid in developing more medical treatments targeted to patients with a specific genetic makeup.

Genomic information also may give individuals information about their risk for a common disease and predict how one will respond to particular medications or environmental exposures, such as radiation from medical tests, according to the U.S. Department of Energy Genome Programs.

Whole-genome sequencing—as opposed to identifying just a subset of genes suspected of being linked to an illness—allows scientists to look broadly across all genes for mutations that are associated with diseases.

This “broad net” approach is particularly useful when researchers don’t have a good sense of which genes might be involved in a disease and may identify a novel drug target, said Richard K. Wilson, director of the Genome Institute at Washington University in St. Louis.

Eventually, if people can be sequenced early in life to learn about health risks, such as aneurysms or early-onset heart attacks, they may be able to take preventive drugs or boost the monitoring of their health, Dr. Wilson said.

With single-gene conditions such as sickle-cell disease, sequencing the whole genome could be useful in identifying “modifier” genes that work with the primary mutation to make a disease more or less severe, Dr. Wilson added.

But understanding how genes work together to cause a condition or to develop a treatment will require extensive laboratory research far beyond merely analyzing the genome, said Karen Kaul, a molecular pathologist at NorthShore University HealthSystem in Evanston, Ill., and spokeswoman for the American Society for Clinical Pathology.

“We are just beginning to scratch the surface about what [genomic] changes are clinically relevant,” she said. “I think we have to be realistic and a little cautious” about current genomic information.

Completion of the Human Genome Project in 2003—which for the first time mapped the human genome—created high expectations that a stream of new drugs would soon flow out of pharmaceutical labs. When that didn’t happen, skeptics questioned the value of the effort.

But in the past year or two, drugs based on genomic information have begun to reach the market.

Still, the wider availability and lower price of sequencing raises the question of how to convert the flood of genetic data into useful information for drug development and treating patients.

“We can sequence the genome for dirt cheap,” said Eric Green, director of the NHGRI, “but we don’t know how to deal with the data. We’ve got to work on that.”

Whether Ion Torrent actually hits the $1,000 target by year’s end won’t be known until the machine and its accompanying technology are delivered and tested by top sequencing centers. Some earlier promises to hit less ambitious price targets by industry participants have failed to meet deadlines or pan out.

Just four years ago, Knome Inc. of Cambridge, Mass., introduced the first commercial human genome, priced at $350,000. Until recently, the high cost largely has limited sequencing to a handful of people, including the late Apple Inc. chief executive, Steve Jobs, according to a recent biography of him by Walter Isaacson.

Even now, only an estimated 1,800 whole genomes have been sequenced using high-quality technology, according to the National Human Genome Research Institute.

Current machines marketed by Illumina Inc. of San Diego, the market leader in sequencing devices, can decode an entire human genome in about a week for about $3,000.

In the wings, said Jeff Schloss, a program director and technology expert at NHGRI, are newer approaches to sequencing that could help drive the price of a genome down to $100.

Jonathan Rothberg, founder of Ion Torrent, is unveiling the machine Tuesday at the annual J.P. Morgan Healthcare conference. It will cost $149,000. The announcement comes amid challenging times for sequencing companies despite the rapid leaps in technology as restraints in government and academic research budgets and the uncertain economy have damped sales of big-ticket sequencers.

“It’s tremendously concerning that at the same time policymakers and law enforcement professionals are waging a war on the growing prescription drug crisis, new super-drugs could well be on their way, flooding the market,” said Sen. Charles Schumer, D-N.Y. “The FDA needs to grab the reins and slow down the stampede to introduce these powerful narcotics.”

A message seeking comment from the Food and Drug Administration was not immediately returned Friday.

The Associated Press reported last month about addiction experts’ fears over four drugs being tested that contain a more powerful version of one of the nation’s most abused painkillers — hydrocodone.

Schumer is particularly concerned about legalizing the drugs for prescriptions because they would be prized commodities in the black market.

Experts say painkiller addiction has been driven partly by a loophole in the 1970 Controlled Substances Act that classified pure hydrocodone — a super painkiller — as a strictly controlled Schedule II drug. But the law put combination products, such as pills containing hydrocodone and acetaminophen, into the less strict Schedule III.

Because of the loophole, patients can refill a prescription for a hydrocodone-acetaminophen drug like Vicodin up to five times. A prescription for a similar oxycodone product, such as Percocet, can be filled only once. Critics say the loophole has flooded American medicine cabinets with hydrocodone.

In 1999, the Drug Enforcement Administration and FDA began reviewing whether they should reschedule hydrocodone combination products. But an AP review of regulatory documents and court filings shows the agencies have repeatedly passed the rescheduling study back and forth, with no final decision made.

A New Year’s Eve robbery at a Long Island pharmacy netted prescription painkillers and cash and left the robber and a federal agent dead. In June, four died in another Long Island pharmacy robbery in which 11,000 hydrocodone pills were stolen.

If the pure hydrocodone drugs are approved, Schumer wants a “robust post-market surveillance” of the drugs as they are marketed, advertised and sold.

Information on the affected bottle sizes, and related expiry dates will be available at www.novartisOTC.com as of January 9, 2012. This precautionary recall follows the recent voluntary suspension of operations and shipments from Novartis Consumer Health Inc’s Lincoln, NE facility. These actions were taken to accelerate maintenance and other improvement activities at the site.

There have been no related adverse event reports received as a result of these issues. The established safety profile for each of these products remains consistent. Mixing of different products in the same bottle could result in consumers taking the incorrect product and receiving a higher or lower strength than intended or receiving an unintended ingredient. This could potentially result in overdose, interaction with other medications a consumer may be taking, or an allergic reaction if the consumer is allergic to the unintended ingredient. NCH is not aware of adverse events reported with the issues leading to the recall. This recall is being conducted with the knowledge of the U.S. Food and Drug Administration (FDA) and Novartis Consumer Health will continue to work closely with the agency as well as its customers throughout this process.

“We are committed to a single quality standard for the entire Novartis Group and we are making the necessary investments and committing the right resources to ensure these are implemented across our entire network,” said Joseph Jimenez, CEO of Novartis. “The high quality of our products and operations has been critical to building the Novartis reputation over the past 15 years. We are committed to ensuring the highest standard for patients who rely on our products and medicines.”

NCH is recalling these products as a precaution due to an internal product review and complaints that identified issues such as broken gelcaps, chipped tablets and inconsistent bottle packaging line clearance practices, where a potential for a tablet mix up could not be ruled out.

NCH plans to gradually resume operations at its Lincoln, NE site following implementation of planned improvements and in agreement with the FDA. The Novartis Consumer Health Inc. Lincoln, NE facility produces a variety of products mainly for the US market with annual sales value of less than 2% of Novartis Group sales. At this stage, it is not possible to determine when the plant will resume full operations and the full financial impact of these events. NCH will take a one-time charge currently estimated at USD 120 million in the fourth quarter of 2011, relating to the recalls and improvement work at the Lincoln, NE facility.

Novartis commitment to quality
Novartis Group is fully committed to ensure the quality, safety and integrity of its products. All Novartis Group companies have a clear commitment to patients and Health Authorities to ensure high quality standards for all our products and services. Novartis Group stands behind the safety and efficacy of its products, and is fully committed to maintaining high quality standards at all production sites in the US and around the world. All Novartis Group products are subjected to strict manufacturing, testing and monitoring standards. Where they fall outside the standards, Novartis Group companies take actions to correct the issue and may recall products as a precaution.

Note to US consumers and customers
Consumers and customers in the US who have questions can call the Consumer Relationship Center at 1-888-477-2403 (available Monday-Friday 9 a.m. to 8 p.m. Eastern Time).

For more detailed information regarding the product, potential drug reactions, impacted configurations, related NDC numbers and expiry dates, please visit our website starting January 9, 2012 at www.novartisOTC.com.

Tobacco industry information can’t be taken at face value, the researchers conclude. They say their work provides evidence that hundreds of additives, including menthol, should be eliminated from cigarettes on public health grounds.

The article is published in PLoS Medicine.

In the new, independent study, the scientists reassessed data from Philip Morris’ “Project MIX,” which detailed chemical analyses of smoke and animal toxicology studies of 333 cigarette additives. Philip Morris, the nation’s largest tobacco company, published its findings in 2002.

By investigating the origins and design of Project MIX, the UCSF researchers conducted their own inquiry into the Philip Morris results. They stressed that many of the toxins in cigarette smoke substantially increased after additives were added to cigarettes.

They also found, after obtaining evidence that additives increased toxicity, that tobacco scientists adjusted the protocol for presenting their results in a way that obscured these increases.

“We discovered these post-hoc changes in analytical protocols after the industry scientists found that the additives increased cigarette toxicity by increasing the number of fine particles in the cigarette smoke that cause heart and other diseases,” said senior author Stanton A. Glantz, PhD, UCSF professor of medicine and director of the Center for Tobacco Control Research and Education at UCSF.

“When we conducted our own analysis by studying additives per cigarette – following Philip Morris’ original protocol — we found that 15 carcinogenic chemicals increased by 20 percent or more,” he said.

Additionally, in the independent study, the researchers discovered the reason behind Philip Morris’ failure to identify many toxic effects in animal studies: its studies were too small.

“The experiment was too small in terms of the number of rats analyzed to statistically detect important changes in biological effects,” Glantz said. “Philip Morris underpowered its own studies.”

The results of “Project MIX” were first published as four papers in a 2002 edition of Food and Chemical Toxicology, a journal whose editor and many members of its editorial board had financial ties to the tobacco industry. While Philip Morris was trying to get the papers published, the company scientist who led Project Mix sent an email to a colleague describing the peer review process as “an inside job.” http://legacy.library.ucsf.edu/tid/ekw86a00/pdf?search=%22inside%20job%20philip%20morris%20project%20mix%20email%22

In the new study, the researchers used documents made public as a result of litigation against the tobacco industry. The documents are available to the public through UCSF’s Legacy Tobacco Documents Library.

Co-authors of the study include Marcia Wertz, RN, PhD, of UCSF’s Department of Social and Behavioral Sciences.

A video describing the paper is available at http://www.scivee.tv/node/37778.

The study was supported by the National Cancer Institute.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Physicians often gravitate to cost control proposals that do not involve their own role and changing their practices, whereas policymakers may propose solutions that will not significantly reduce costs. In assessing cost control proposals, 2 criteria are fundamental. One criterion is that 2% growth in health care costs over growth in GDP amounts to $52 billion a year; serious proposals are aimed at reducing the growth in health care costs to 1% over GDP growth. Consequently, anything short of $26 billion in savings is not credible. A second criterion is that cost control proposals should transform the delivery of care and lead to improved quality as well as patient and physician satisfaction.

Malpractice Costs.. Physicians frequently cite malpractice premiums and the cost of defensive medicine as drivers of high costs. A recent Congressional Budget Office (CBO) analysis estimated that a package of reforms consisting of a $250 000 cap on noneconomic damages, a $500 000 cap on punitive damages, reducing the statute of limitations (1 year for adults and 3 years for children), and implementing fair-share liability could reduce malpractice premiums by 10% ($3.5 billion per year) and reduce defensive medicine for the entire health care system by 0.3% ($7 billion), for a total savings of approximately $11 billion or 0.5% of national health care spending per year.^3​ No reliable data indicate that other malpractice reforms would generate cost savings.

Importantly, more than 30 states have instituted similar caps and limits. If these measures have reduced costs, they are insufficient to counter other factors increasing costs. In addition, physicians in those states, such as California, do not seem to indicate that the practice environment is better. There is little research on the effects of malpractice caps on quality, although 1 study cited by the CBO suggested that caps lowered the quality of care.⁴ This suggests that limits on malpractice liability would not likely both reduce costs and improve quality.

Insurance Company Profits. Another proposed cost control mechanism focuses on the profits of insurance companies. In 2010, the combined profits of the 5 largest insurers—Wellpoint, United, Aetna, Humana, and Cigna—increased substantially, reaching $11.7 billion.^5​ It may be worthy to reduce these profits, but in the scheme of $2.6 trillion in national health care spending, this amount constitutes just 0.5% of total spending.

Drug Costs. In 2010, the United States spent $262 billion on prescription drugs, 10% of total health care spending.¹ There is a worrisome trend that new drugs and biologics costing tens of thousands of dollars per year do not provide cures, but achieve only modest disease benefit. One approach to cost savings is drug reimportation, which would allow brand-name drugs sold at lower prices in Canada or other countries to be imported into the United States. Assuming the logistical and supply problems were solved, the CBO estimated that reimportation could save approximately 1% of drug costs, an insignificant $2.6 billion.^6​

Another approach might be to substitute generic drugs for brand-name drugs. Between 2004 and 2009, use of generic drugs increased substantially from 57% to 75% of all prescriptions.⁷ Despite this change, costs for health care and for prescription drugs have both increased by approximately 25% during those years. By increasing generic prescription levels to 100%—an unrealistic level—CBO estimated that an additional $900 million could be saved for Medicare Part D in 2009.^8​ Of the $502 billion spent on Medicare in 2009, this would amount to a savings of less than 0.2%. The US Department of Health and Human Services recently concluded that increased savings from expanding generic use “are likely to be small relative to total spending on drugs”⁷—not to mention total health care costs.

“The Million Dollar Baby.” Many physicians believe the US health care system expends excessive amounts on so-called “million dollar babies”—patients who spend long periods in intensive care units and require tracheostomies, gastrostomy tubes, and myriad other interventions. However, an analysis of nearly 20 million commercially insured patients revealed that only 255 patients had consumed more than $1 million each on health care expenditures in 2010. Extrapolating to the entire health care system suggests these patients use 0.5% of all health care costs. Even if all costs attributed to care of these “million dollar babies” could be eliminated, there are not enough of such patients to significantly reduce health care spending. Expanding this group to patients who consume more than $250 000 in health care expenditures each per year would translate into 6.5% of health care costs. But how can these high-cost patients be identified before they get treatment? Furthermore, it would not seem possible to curtail the health care services such patients receive without raising the charge of “death panels.”

Some may suggest that even if each of these individual cost control measures does not save much money, all together the savings might begin to approach $15 or $20 billion. Maybe. However, there are no specific policies that would enable saving money on the care of “million dollar babies” and the probability of policies that would foster adoption in other areas is remote. More importantly, none of these 4 cost control approaches would transform the delivery of care and generate higher-quality care more efficiently. Malpractice reform based on caps to damages has the suggestion of lowering quality, reimportation of drugs and reducing insurers’ profits lower prices but do not affect the delivery of care or quality, and money saved on the “million dollar babies” cannot be anticipated.

Where Are the Cost Savings?

Where is the money in health care? Approximately 10% of the population consumes about 64% of health care expenditures. Who are these patients? “Chronic conditions were closely linked to high expenditure levels: more than 75% of high-cost beneficiaries . . . had one or more of seven major chronic conditions . . . 42% had coronary artery disease, 30% had congestive heart failure, and 30% had diabetes.”^9​ Another reason to focus on these patients is to improve quality—they use the majority of health care services.

There are 2 important aspects about their health care spending and quality of care. First, one estimate suggested that as much as 22% of all health care expenditures is related to potentially avoidable complications such as hospital admissions for patients with diabetes with ketoacidosis or amputation of gangrenous limbs or of patients with congestive heart failure for shortness of breath due to fluid overload.¹⁰ Thus, reducing avoidable complications by 10% could save more than $40 billion per year.

Second, reducing unnecessary medical care for chronically ill patients is about improving tertiary prevention. While some efforts to improve tertiary prevention have failed, others have succeeded. Development and dissemination of additional approaches are needed. Successful efforts seem to entail instituting at least 4 common changes: (1) installing electronic health records and using them to track patients’ health status and physician performance, as well as using decision supports to increase adherence to treatment pathways; (2) using the information for more intensive interactions between patients, caregivers, and clinic staff, including use of care coordinators, 24/7 access, interventions to increase medication adherence, specialized clinic services for recurrent problems of patients with chronic disease such as anticoagulation clinics; (3) reducing use of specialists, and when specialists are involved using those who are more efficient; and (4) providing services not traditionally covered by fee-for-service reimbursement, such as e-mail, wireless monitoring to increase medication adherence, home evaluations to minimize falls, lifestyle interventions to improve nutrition and exercise, and transportation services for office visits. Cumulatively, the savings appear to occur through fewer hospitalizations, emergency department visits, and lower use of specialist services.

The Role of Physicians

For physicians to know “where the money is” and the availability of some successful models for reducing costs has 3 implications. First, physicians must be the leaders and must stop looking to drug companies, insurers, or someone else to initiate and achieve cost savings.

Second, physicians have the responsibility to redesign care delivery to emphasize more tertiary prevention and avoid unnecessary complications. Although this will be hard work, only effective physician leadership can ensure successful redesign.

Third, physicians know well that such care redesign cannot occur without payment reform. Rather than complain about the payment system and reimbursement rates, and the problems of accountable care organization regulations or bundled payment regulations, physicians need to take the initiative. They need to develop and propose bundled payments or suggest revisions to the new regulations on accountable care organizations that will facilitate the redesign of care and tertiary prevention.

Deficit pressures are making cost control inevitable. It will only be successful if physicians stop looking to others to find solutions and focus on approaches that improve the care for patients with chronic illnesses.

Author Information

Corresponding Author: Ezekiel J. Emanuel, MD, PhD, Office of the Provost and Department of Medical Ethics and Health Policy, University of Pennsylvania School of Medicine, 122 College Hall, Philadelphia, PA 19104 (zemanuel@upenn.edu).

REFERENCES

. Recession contributes to slowest annual rate of increase in health spending in five decades. Health Aff (Millwood). 2011;30(1):11–22, pmid:21209433.Free Full Text

. The Long-Term Outlook for Health Care Spending. http://www.cbo.gov/ftpdocs/87xx/doc8758/MainText.3.1.shtml. Accessed November 30, 2011.

. Selected CBO Publications Related to Health Care Legislation, 2009-2010: Effect of Proposals to Limit Costs Related to Medical Malpractice (Tort reform). http://www.cbo.gov/ftpdocs/120xx/doc12033/12-23-SelectedHealthcarePublications.pdf. Accessed November 30, 2011.

. Evaluation of Options for Medical Malpractice System Reform. http://www.medpac.gov/documents/Apr10_MedicalMalpractice_CONTRACTOR.pdf. Accessed November 30, 2011.

. HCAN Analysis Shows Health Insurers Pocketed Huge Profits in 2010 Despite Weak Economy. http://healthjusticenetwork.wordpress.com/2011/03/04/hcan-analysis-shows-health-insurers-pocketed-huge-profits-in-2010-despite-weak-economy/. Accessed November 30, 2011.

. H.R. 2427: The Pharmaceutical Market Access Act of 2003, CBO Cost Estimate: November 19, 2003. http://www.cbo.gov/ftpdocs/48xx/doc4852/hr2427.pdf. Accessed December 7, 2011.

. ASPE Issue Brief: Expanding the Use of Generic Drugs: December 1, 2010. http://aspe.hhs.gov/sp/reports/2010/GenericDrugs/ib.pdf. Accessed November 30, 2011.

. Effects of Using Generic Drugs on Medicare’s Prescription Drug Spending. http://www.cbo.gov/doc.cfm?index=11838. Accessed November 30, 2011.

. The high concentration of US health care expenditures. Research in Action. 2006:19. http://www.ahrq.gov/research/ria19/expendria.pdf. Accessed November 30, 2011.

. Building a bridge from fragmentation to accountability: the Prometheus Payment model. N Engl J Med. 2009;361(11):1033–1036, pmid:19692682.Find Full-TextCrossRefMedline

[medpagetoday] Drug research, even from clinical trials sponsored by the federal government, routinely is suppressed, harming patients and increasing healthcare costs, according to a series of reports published by BMJ.

“The current situation is a disservice to research participants, patients, health systems, and the whole endeavor of clinical medicine,” according to an editorial published with the reports.

A solution, according to Richard Lehman, MD, a consultant psychiatrist at the University of Oxford, and Elizabeth Loder, MD, MPH, a contributing editor at BMJ, would be to subject researchers who withhold data to “disciplinary action by professional organizations.”

An unexpected finding in the BMJ analysis was that serious lapses appear to have occurred in clinical trials funded by the National Institutes of Health.

According to the analysis, less than half of NIH-funded clinical trials were published in a medical journal within 30 months of the completion of the trial and after 51 months, one-third of trials remained unpublished.

While industry-related profit motives may not be a factor in such cases, there are other possible explanations, said senior author Harlan Krumholz, MD, of Yale University.

Sometimes researchers may get an unexpected finding that contradicts a position they have staked out, he said.

“It is a conflict of their academic beliefs,” he said.

At the same time, medical journals may not want to publish negative findings, he said.

A second BMJ paper assessed clinical trials of drugs that already had received at least one Food and Drug Administration approval. In such cases a law requires the reporting within one year of the completion of the trial.

Despite the law, only 163 of 738 such trials, or 22%, had reported the results within a year, the paper found.

Lead author Andrew Prayle, PhD, a researcher with the University of Nottingham, in England, said he hoped the finding would spur more researchers to post summaries of the work at the NIH site, ClinicalTrials.gov.

The BMJ papers are just the latest salvos in an ongoing controversy over both industry support of research and control of raw data from trials.

“It is grossly unethical and an insult to the integrity of medicine when this is allowed to occur and go unpunished,” said orthopedic surgeon Chuck Rosen, MD, president of the Association for Medical Ethics.

From diabetes drugs to spine surgery products, scandals involving concealed data have mounted. Consider the cases of a trio of drugs that were the subject of Journal Sentinel/MedPage Today articles:

For two years, Schering-Plough, the maker of the popular cholesterol drug Vytorin, sat on the results of a clinical trial showing the drug provided no benefit in improving artery health. During that time the drug was heavily marketed to consumers in TV ads. The situation came to light in 2008 after a congressional investigation was launched.

In 2003, a clinical trial of Multaq, a drug that treated irregular heart beat, was stopped because more patients who were getting the drug were dying than those who were getting a placebo. However, the study was not published until five years later.

In 2007, an independent analysis of the diabetes drug Avandia found that the drug increased heart attacks and cardiovascular deaths.

Steven Nissen, MD, the lead author of the analysis, said 35 of the 42 studies he looked at were unpublished and were obtained only because a court case required the drug’s maker, GlaxoSmithKline, to turn over the data.

“Had the medical community known about this hazard, Avandia would likely never have become the world’s largest selling diabetes drug,” said Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. “Our ability to provide the best care for patients is dependent on access to all of the available clinical trial evidence, regardless of whether the study showed favorable results.”

While much of the criticism of suppressed medical research has been aimed at drug companies, research data from medical devices also has been delayed, especially when it reflects negatively on a product.

Critics pointed to Medtronic’s bone-growth stimulating back surgery product known as Infuse.

Last year, the Journal Sentinel/MedPage Today reported that the results of a crucial clinical trial of the product were not published until nearly five years after the trial had to be halted because unwanted bone was growing around the spines of the trial volunteers. The paper was written by surgeons who have received millions of dollars in royalties from other Medtronic spine products.

What’s more, the authors of the belated paper downplayed the bone overgrowth, saying it did not harm patients, a claim that was flatly refuted by a doctor interviewed by the Journal Sentinel/MedPage Today.

The doctor, an Oklahoma orthopedic surgeon, said two of his patients who were in the trial had to undergo additional surgery because the bone overgrowth was painfully impinging on nerve roots. One of the patients, a man who was in his 50s at the time, needed three operations — one for the implant, a second to remove the unwanted bone formation, and a third when the additional bone grew back yet again.

Independent research and Journal Sentinel stories since have noted that unpublished data showed that Infuse was linked to a variety of serious complications, including sterility in men and cancer.

The failure of the medical literature to report such findings “has been a major failure in our field,” said Eugene Carragee, MD, a Stanford University orthopedic surgeon and editor-in-chief of the Spine Journal.

Carragee said the BMJ analysis and its call for disciplinary action against offending doctors is “an important departure from the historical laissez-faire attitude of the recent past.”

By John Fauber, Reporter, Milwaukee Journal Sentinel/MedPage

The Argentinian Federation of Health Professionals accuses drug maker GlaxoSmithKline of misleading participants and pressuring poor families into joining a trial for the Synflorix vaccine, which the company says protects against bacterial pneumonia and meningitis.

“They recruited children in an irregular manner. … They did not do what they were supposed to. They did not inform. There were not independent witnesses. They pressured the mothers of poor children,” said Jorge Yabkowsky, the federation’s director.

But GlaxoSmithKline, the world’s second largest pharmaceutical company, denies those accusations and says it will appeal a judge’s approval of Argentina’s National Administration of Medicine, Food and Medical Technology’s fining the company and two doctors a total of nearly $240,000 for irregularities in documentation of the trial.

In a statement, GlaxoSmithKline said it conducts clinical studies all over the world, respecting laws and meeting the highest standards of ethics and quality.

“The ruling has to do with procedures, with the form of documenting procedures of the studies. … None of the patients that were included in this study were included without their appropriate consent,” said Rosana Felice, medical director of Glaxo Argentina.

Felice said official investigations by Argentina’s drug administration, known as ANMAT, and ethics reviews have not turned up any irregularities in the vaccine’s safety.

GlaxoSmithKline’s statement said there are no cases alleging fraud or corruption in the study.

The deaths of 14 children who reportedly died after participating in the trials, have drawn widespread attention in Argentinian media. Their deaths are under investigation, but there has been no evidence linking deaths to the vaccine or irregularities in the studies.

Felice said GlaxoSmithKline categorically denies that the vaccine caused the deaths.

“In no case was it related to the administration of the vaccine, and this has been sufficiently demonstrated, proven and evaluated by ANMAT,” Felice said.

But the health professional federation pointed to the children’s deaths in its call for increased regulations on drug testing.

The trial included 24,000 children, Felice said, including 14,000 children in Argentina and 10,000 others in Colombia and Panama.

The Synflorix vaccine has been approved by regulatory agencies in more than 85 countries, based on more than 40 clinical studies, GlaxoSmithKline said.