Unsafe Drugs Were Prescribed More Than One Hundred Million Times in the United States Before Being Recalled

By Sonali Saluja, Steffie Woolhandler, David U. Himmelstein, David Bor, Danny McCormick
The International Journal of Health Services, June 14, 2016

Abstract

For some drugs, safety concerns are only discovered after they have been on the market, sometimes for several years. The U.S. Food and Drug Administration (FDA) has adopted several policies that could increase the likelihood of approving a potentially unsafe medication. We attempted to quantify the number of exposures in the United States to drugs that were newly approved but later withdrawn from the market. We obtained a list of all drugs approved and subsequently withdrawn from the U.S. market due to safety concerns between 1993 and 2010. Using a representative sample of outpatient physician office visits in the National Ambulatory Medical Care Survey, we estimated the number of visits in the United States at which these unsafe drugs were prescribed. Seventeen drugs were approved and later withdrawn during this 18-year period and were prescribed at 112 million physician office visits in the United States. Nine of these drugs were prescribed more than 1 million times before their market withdrawal. New drugs that are later withdrawn due to being unsafe are frequently prescribed in the United States. To minimize the negative health consequences of prescribing potentially unsafe medications, we should reconsider some of the FDA policies that encourage the rapid approval and dissemination of new drugs.

From the Introduction

Each year more than 2 million serious adverse drug reactions occur in the United States, causing an estimated 100,000 deaths. Many safety problems emerge only after drugs have received Food and Drug Administration (FDA) approval. Indeed, in the first 16 years after approval, 27 market withdrawals and serious new safety warnings—so-called black box warnings (BBWs)—are issued for every 100 newly introduced drugs. For withdrawn drugs, the median time from FDA approval to removal from the market is five years.

The FDA initiated a series of programs in the 1980s and 1990s that allowed the expedited review of certain drugs. Perhaps as a consequence of these programs, the FDA approves new drugs significantly faster than the regulatory bodies of Europe, Canada, and Japan. Unlike the United States, most European Union countries require that new drugs undergo a secondary review process comparing their efficacy to the existing standard of care before health insurance plans will pay for them. Furthermore, the European Union, Canada, and Japan prohibit direct-to-consumer advertising, which is known to increase prescribing of the advertised drug.

Pharmaceutical firms often heavily market newly approved medications in the United States, and doctors frequently prescribe them. After the FDA relaxed regulations on direct-to-consumer advertising in 1997, including allowing less reporting of product risks, pharmaceutical spending on advertising increased more than three-fold. Patients commonly ask for advertised drugs in the United States and clinicians often feel pressured to prescribe them. Hence, many Americans may be exposed to drugs that pose a risk to their health before their dangers are adequately appreciated.

From the Discussion

This descriptive study is the first systematic attempt to quantify the extent to which the U.S. population is exposed to unsafe drugs in the outpatient setting.

Special FDA programs that allow for the expedited review of some drugs are now commonly used by industry to gain quick access to the U.S. market. Expedited reviews were initiated in the 1980s to allow for rapid approval of HIV drugs. These programs were intended for drugs used in exceptional circumstances: for life-threatening, untreatable, or rare diseases. However, the pharmaceutical industry now frequently uses these programs in non-exceptional circumstances; currently, the majority of new drugs qualify for expedited review. This year the U.S. Congress will consider additional legislation, the 21st Century Cures Act, that would further accelerate approval of some drugs and could expose millions more Americans to medications that have been only briefly studied for safety.

Several policy steps might reduce patients’ exposure to unsafe drugs, including: returning to a more stringent FDA approval process, increasing post-marketing surveillance, and eliminating direct-to-consumer advertising.

http://joh.sagepub.com/content/early/2016/06/10/0020731416654662.abstract

***

Comment:

By Don McCanne, M.D.

Since it is impossible to read all of the research studies on new drugs, we can be thankful that we have the Food and Drug Administration (FDA) to collate and evaluate all of that information so that we know that new drug products released on the market have been demonstrated to be both effective and safe. Or can we? This new study adds to our concerns.

With the politics in our nation being under the control of the pro-market neoliberals and conservatives, the pharmaceutical industry and insurance companies have been given a most favored status under the belief that markets will serve the public better if not constrained by supposedly excessive government oversight.

In the case of pharmaceuticals, the public can experience the benefits earlier of the new blockbuster miracle drugs if the government (FDA) will just get out of the way, or so they say. More recent laws and regulations have allowed pharmaceutical firms to pay fees to enter an accelerated process for new drug approval (like buying their way to the front of the queue). This accelerated process has been expanded to include most new drugs, ignoring the fact that there may be a conflict of interest when firms can buy off government regulators to expedite approval of their products.

To be sure that the information evaluated truly represents the value of the new drugs, pharmaceutical firms have agreed to register all studies in advance and not just the studies with favorable results. But research studies with adverse results are still being filed away without public oversight, explaining some of the reason that drugs on the market do not have the same benefits and safety margin as the pre-marketing studies submitted to the FDA show. Also the firms have promised close post-marketing surveillance, but that seems to disappear once the drug is approved. Also the firms are not required to compare new drugs with existing drugs even though many turn out to be inferior. Yet with our lax rules on direct-to-consumer advertising, a demand can be created for these new drugs in spite of their typically outrageous prices. Now Congress is advancing the CURES Act to further benefit the biomedical firms, potentially at a cost to the public’s health that may offset the benefits.

This problem is serious. The study by Saluia et al. shows that over 100 million prescriptions were issued for drugs that had to be withdrawn from the market because they proved to be unsafe. About 100,000 people die each year from drug reactions, and this is particularly tragic when it is from a drug that never should have been on the market in the first place.

The stewards of a well designed single payer system would demand much better performance from the pharmaceutical industry – drugs and other biomedical products that are effective, that are an improvement over existing treatments, that are reasonably safe, and that are priced appropriately based on legitimate costs and a fair profit margin. Regardless, the government has to step up if we want better quality and value in our nation’s drug supply.

Unsafe Drugs Were Prescribed More Than One Hundred Million Times in the United States Before Being Recalled

By Sonali Saluja, Steffie Woolhandler, David U. Himmelstein, David Bor, Danny McCormick
The International Journal of Health Services, June 14, 2016

Abstract

For some drugs, safety concerns are only discovered after they have been on the market, sometimes for several years. The U.S. Food and Drug Administration (FDA) has adopted several policies that could increase the likelihood of approving a potentially unsafe medication. We attempted to quantify the number of exposures in the United States to drugs that were newly approved but later withdrawn from the market. We obtained a list of all drugs approved and subsequently withdrawn from the U.S. market due to safety concerns between 1993 and 2010. Using a representative sample of outpatient physician office visits in the National Ambulatory Medical Care Survey, we estimated the number of visits in the United States at which these unsafe drugs were prescribed. Seventeen drugs were approved and later withdrawn during this 18-year period and were prescribed at 112 million physician office visits in the United States. Nine of these drugs were prescribed more than 1 million times before their market withdrawal. New drugs that are later withdrawn due to being unsafe are frequently prescribed in the United States. To minimize the negative health consequences of prescribing potentially unsafe medications, we should reconsider some of the FDA policies that encourage the rapid approval and dissemination of new drugs.

From the Introduction

Each year more than 2 million serious adverse drug reactions occur in the United States, causing an estimated 100,000 deaths. Many safety problems emerge only after drugs have received Food and Drug Administration (FDA) approval. Indeed, in the first 16 years after approval, 27 market withdrawals and serious new safety warnings—so-called black box warnings (BBWs)—are issued for every 100 newly introduced drugs. For withdrawn drugs, the median time from FDA approval to removal from the market is five years.

The FDA initiated a series of programs in the 1980s and 1990s that allowed the expedited review of certain drugs. Perhaps as a consequence of these programs, the FDA approves new drugs significantly faster than the regulatory bodies of Europe, Canada, and Japan. Unlike the United States, most European Union countries require that new drugs undergo a secondary review process comparing their efficacy to the existing standard of care before health insurance plans will pay for them. Furthermore, the European Union, Canada, and Japan prohibit direct-to-consumer advertising, which is known to increase prescribing of the advertised drug.

Pharmaceutical firms often heavily market newly approved medications in the United States, and doctors frequently prescribe them. After the FDA relaxed regulations on direct-to-consumer advertising in 1997, including allowing less reporting of product risks, pharmaceutical spending on advertising increased more than three-fold. Patients commonly ask for advertised drugs in the United States and clinicians often feel pressured to prescribe them. Hence, many Americans may be exposed to drugs that pose a risk to their health before their dangers are adequately appreciated.

From the Discussion

This descriptive study is the first systematic attempt to quantify the extent to which the U.S. population is exposed to unsafe drugs in the outpatient setting.

Special FDA programs that allow for the expedited review of some drugs are now commonly used by industry to gain quick access to the U.S. market. Expedited reviews were initiated in the 1980s to allow for rapid approval of HIV drugs. These programs were intended for drugs used in exceptional circumstances: for life-threatening, untreatable, or rare diseases. However, the pharmaceutical industry now frequently uses these programs in non-exceptional circumstances; currently, the majority of new drugs qualify for expedited review. This year the U.S. Congress will consider additional legislation, the 21st Century Cures Act, that would further accelerate approval of some drugs and could expose millions more Americans to medications that have been only briefly studied for safety.

Several policy steps might reduce patients’ exposure to unsafe drugs, including: returning to a more stringent FDA approval process, increasing post-marketing surveillance, and eliminating direct-to-consumer advertising.

http://joh.sagepub.com/content/early/2016/06/10/0020731416654662.abstract

Since it is impossible to read all of the research studies on new drugs, we can be thankful that we have the Food and Drug Administration (FDA) to collate and evaluate all of that information so that we know that new drug products released on the market have been demonstrated to be both effective and safe. Or can we? This new study adds to our concerns.

With the politics in our nation being under the control of the pro-market neoliberals and conservatives, the pharmaceutical industry and insurance companies have been given a most favored status under the belief that markets will serve the public better if not constrained by supposedly excessive government oversight.

In the case of pharmaceuticals, the public can experience the benefits earlier of the new blockbuster miracle drugs if the government (FDA) will just get out of the way, or so they say. More recent laws and regulations have allowed pharmaceutical firms to pay fees to enter an accelerated process for new drug approval (like buying their way to the front of the queue). This accelerated process has been expanded to include most new drugs, ignoring the fact that there may be a conflict of interest when firms can buy off government regulators to expedite approval of their products.

To be sure that the information evaluated truly represents the value of the new drugs, pharmaceutical firms have agreed to register all studies in advance and not just the studies with favorable results. But research studies with adverse results are still being filed away without public oversight, explaining some of the reason that drugs on the market do not have the same benefits and safety margin as the pre-marketing studies submitted to the FDA show. Also the firms have promised close post-marketing surveillance, but that seems to disappear once the drug is approved. Also the firms are not required to compare new drugs with existing drugs even though many turn out to be inferior. Yet with our lax rules on direct-to-consumer advertising, a demand can be created for these new drugs in spite of their typically outrageous prices. Now Congress is advancing the CURES Act to further benefit the biomedical firms, potentially at a cost to the public’s health that may offset the benefits.

This problem is serious. The study by Saluia et al. shows that over 100 million prescriptions were issued for drugs that had to be withdrawn from the market because they proved to be unsafe. About 100,000 people die each year from drug reactions, and this is particularly tragic when it is from a drug that never should have been on the market in the first place.

The stewards of a well designed single payer system would demand much better performance from the pharmaceutical industry – drugs and other biomedical products that are effective, that are an improvement over existing treatments, that are reasonably safe, and that are priced appropriately based on legitimate costs and a fair profit margin. Regardless, the government has to step up if we want better quality and value in our nation’s drug supply.