Latest Drugwonks' Blog
FDA Says Consumers Continue to Buy Risky Drugs Online
Self-medication a concern; FDA-approved generics may be cheaper alternative
A yearlong U.S. Food and Drug Administration (FDA) investigation into drugs mailed to the United States from foreign countries suggests that consumers may be buying drugs online to avoid the need for a prescription from their physician. The FDA sampling of imported drugs also indicates that consumers continue to spend money unnecessarily on potentially risky drug products bought over the Internet.
The investigation found 88 percent of the 2,069 drug packages examined appeared to be prescription medicines available in the United States. Of the remaining products, some were dietary supplements, some were foreign products with labeling that was illegible or incomprehensible, and some were medications not available in the United States. More than half (53 percent) of the products sampled have FDA-approved generic versions, likely sold at lower costs, according to earlier studies that have shown generics in the United States to be generally cheaper than a comparable drug in Canada or Western Europe. In fact, approved generic versions of approximately half (47 percent) of the sampled products can be bought for $4 at several national chain pharmacies, a price often lower than the shipping costs for the same drugs purchased online.
"The data lead us to believe that many people are buying drugs online not to save money but to bypass the need for a prescription from their doctor since these Web sites typically do not require the purchaser to have a prescription," said Randall Lutter, Ph.D., FDA's deputy commissioner for policy. "In essence, they seem to be getting and using prescription drugs without a prescription, an intrinsically risky practice."
These data are based on surveys conducted from September 2006 to August 2007 in international mail facilities and courier facilities across the country. At each city, all parcels suspected by customs and border patrol of containing pharmaceuticals were stopped for a period of 24 hours. FDA then recorded data on the contents of these parcels, before handling them in accordance with its usual procedures.
In general, a Web site can appear legitimate, but in fact be a front for an illegal operation. FDA urges consumers to beware of unregulated Internet drug sellers, because many of their products might not contain the correct ingredients and could contain toxic substances. Several drugs found in this survey require special monitoring by physicians or other health care professionals for potential adverse events and to ensure their effectiveness. These include antibiotics, antidepressants, the blood thinner warfarin, and levothyroxine (a thyroid replacement hormone).
Self-medication a concern; FDA-approved generics may be cheaper alternative
A yearlong U.S. Food and Drug Administration (FDA) investigation into drugs mailed to the United States from foreign countries suggests that consumers may be buying drugs online to avoid the need for a prescription from their physician. The FDA sampling of imported drugs also indicates that consumers continue to spend money unnecessarily on potentially risky drug products bought over the Internet.
The investigation found 88 percent of the 2,069 drug packages examined appeared to be prescription medicines available in the United States. Of the remaining products, some were dietary supplements, some were foreign products with labeling that was illegible or incomprehensible, and some were medications not available in the United States. More than half (53 percent) of the products sampled have FDA-approved generic versions, likely sold at lower costs, according to earlier studies that have shown generics in the United States to be generally cheaper than a comparable drug in Canada or Western Europe. In fact, approved generic versions of approximately half (47 percent) of the sampled products can be bought for $4 at several national chain pharmacies, a price often lower than the shipping costs for the same drugs purchased online.
"The data lead us to believe that many people are buying drugs online not to save money but to bypass the need for a prescription from their doctor since these Web sites typically do not require the purchaser to have a prescription," said Randall Lutter, Ph.D., FDA's deputy commissioner for policy. "In essence, they seem to be getting and using prescription drugs without a prescription, an intrinsically risky practice."
These data are based on surveys conducted from September 2006 to August 2007 in international mail facilities and courier facilities across the country. At each city, all parcels suspected by customs and border patrol of containing pharmaceuticals were stopped for a period of 24 hours. FDA then recorded data on the contents of these parcels, before handling them in accordance with its usual procedures.
In general, a Web site can appear legitimate, but in fact be a front for an illegal operation. FDA urges consumers to beware of unregulated Internet drug sellers, because many of their products might not contain the correct ingredients and could contain toxic substances. Several drugs found in this survey require special monitoring by physicians or other health care professionals for potential adverse events and to ensure their effectiveness. These include antibiotics, antidepressants, the blood thinner warfarin, and levothyroxine (a thyroid replacement hormone).
Headline in today’s edition of the Wall Street Journal reports on a new IMS report that, “Prescription-Drug Sales Growth Is Expected to Slow.â€
Here’s a link to the complete WSJ story:
http://online.wsj.com/article/SB119387833538878513.html?mod=dist_smartbrief
What the headline means is that the sales volume of on-patent drugs will slow, not that the use of pharmaceutical products will decrease. Important distinction.
As the WSJ reports, “IMS forecasts that about two-thirds of prescriptions dispensed in the U.S. next year will be generics, up from 50% in 2003.â€
The article also comments on the pipeline and regulatory environment, “Drug companies, meanwhile, aren't churning out enough new medicines to keep dollar sales growing at the same pace. And regulators such as the Food and Drug Administration, burned by several drug-safety scandals, are casting a tougher eye on new products before allowing them on the market.â€
First, as to the FDA “casting a tougher eye,†the agency always casts a tough, educated, professional eye on its actions. And new legislation gives the FDA even more authority and funding to do its job better. “Better†not “Tougher†– it’s an important distinction.
As to the fact that drug companies aren’t “churning out†enough new medicines, one thought – new drugs are never “churned out.†That’s a pretty glib statement considering that, despite the increase in R&D spending, the number of new innovative products being submitted to the FDA for approval is decreasing. In fact, output of new products has been dropping since 1997. FDA is now receiving fewer applications for new drugs than in mid-1990’s. The number of new device applications is also decreasing.
And the rate of failure is increasing. Almost 50% of applications are failing in late-stage Phase 3 trials. This costs companies millions of extra dollars and is driving up the cost of successfully bringing a new drug to market. In 2003, researchers at Tufts Center for the Study of Drug Development estimated these costs to be $802 million, and some sources suggest that the total cost is closer to $1.7 billion.
As the late US Senator Everitt Dirksen once said, “A billion here and a billion there, and pretty soon you’re talking about real money.â€
The high cost of R&D is forcing many companies to make the short-term business decision to focus product-development on those molecules that have a much higher potential to recoup expenditures. Unfortunately, this trumps attempts to develop potentially risky but breakthrough products for diseases affecting smaller populations, the orphan drugs.
Consider the implications if FDA could help companies to fail faster. Using the lower end of the Tufts drug development number …
* A 10% improvement in predicting failure before clinical trials could save $100 million in development costs.
* Shifting 5% of clinical failures from Phase 3 to Phase 1 reduces out of pocket costs by $15-$20 million
* Shifting ¼ of failures from Phase 2 to Phase 1 would reduce out of pocket costs by $12-$21 million.
Hence the urgency of the FDA’s Critical Path program.
Here’s a link to the complete WSJ story:
http://online.wsj.com/article/SB119387833538878513.html?mod=dist_smartbrief
What the headline means is that the sales volume of on-patent drugs will slow, not that the use of pharmaceutical products will decrease. Important distinction.
As the WSJ reports, “IMS forecasts that about two-thirds of prescriptions dispensed in the U.S. next year will be generics, up from 50% in 2003.â€
The article also comments on the pipeline and regulatory environment, “Drug companies, meanwhile, aren't churning out enough new medicines to keep dollar sales growing at the same pace. And regulators such as the Food and Drug Administration, burned by several drug-safety scandals, are casting a tougher eye on new products before allowing them on the market.â€
First, as to the FDA “casting a tougher eye,†the agency always casts a tough, educated, professional eye on its actions. And new legislation gives the FDA even more authority and funding to do its job better. “Better†not “Tougher†– it’s an important distinction.
As to the fact that drug companies aren’t “churning out†enough new medicines, one thought – new drugs are never “churned out.†That’s a pretty glib statement considering that, despite the increase in R&D spending, the number of new innovative products being submitted to the FDA for approval is decreasing. In fact, output of new products has been dropping since 1997. FDA is now receiving fewer applications for new drugs than in mid-1990’s. The number of new device applications is also decreasing.
And the rate of failure is increasing. Almost 50% of applications are failing in late-stage Phase 3 trials. This costs companies millions of extra dollars and is driving up the cost of successfully bringing a new drug to market. In 2003, researchers at Tufts Center for the Study of Drug Development estimated these costs to be $802 million, and some sources suggest that the total cost is closer to $1.7 billion.
As the late US Senator Everitt Dirksen once said, “A billion here and a billion there, and pretty soon you’re talking about real money.â€
The high cost of R&D is forcing many companies to make the short-term business decision to focus product-development on those molecules that have a much higher potential to recoup expenditures. Unfortunately, this trumps attempts to develop potentially risky but breakthrough products for diseases affecting smaller populations, the orphan drugs.
Consider the implications if FDA could help companies to fail faster. Using the lower end of the Tufts drug development number …
* A 10% improvement in predicting failure before clinical trials could save $100 million in development costs.
* Shifting 5% of clinical failures from Phase 3 to Phase 1 reduces out of pocket costs by $15-$20 million
* Shifting ¼ of failures from Phase 2 to Phase 1 would reduce out of pocket costs by $12-$21 million.
Hence the urgency of the FDA’s Critical Path program.
Without fanfare or media coverage the European Medicines Agency reaffirmed that use of epo shoudl be handled by doctors -- not by bureaucrats -- and that there should be no hard and fast hemoglobin level imposed from above, rather a flexible level achieved as befits the needs and quality of life of individual patients.
That puts Europe light years ahead of our CMS that has deemed it cost effective and safe to toss tons of seniors into the dark ages of blood transfusions. I wonder what Pharmalot and others who had predicted a tightening of EMEA guidelines will say? Ditto the fact that the EMEA also took a mature approach to Avandia. But that is a post for another day.
For now, it is clear that CMS over-reached using the wrong data to achieve an over-restrictive decision inconsistent with the emergence of patient-centric medicine. EMEA is moving in that direction. So is FDA. Both have Critical Path programs designed to integrate the tools and knowledge to promote patient variation into the development and use of new drugs. Why not a Critical Path for CMS to achieve the same goal in developing insights into the value of new treatments?
So here's my proposal for a Critical Path for Comparative Effectiveness for CMS. Comments and thoughts welcome.
CMS should initiate a Critical Path for comparative effectiveness much as the FDA developed a Critical Path for drug approval and development. “The Critical Path Initiative is FDA's effort to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured.†CMS needs to initiate in a manner that is as transparent and as collaborative as that undertaken by the FDA to promote a national effort to modernize the science information the evaluation of the value of treatments. Just as the key scientific insights guiding the FDA critical path are genetic variations and biomedical informatics that predict and inform individual responses to treatment, CMS needs to establish a process to incorporate knowledge and tools that personalize evidence of response in its decisions.
It should to the extent possible use coverage to evidence development, research grants and partnerships with industry, the FDA, NIH, the new Reagan-Udall Critical path institute to “ harness the potential of bioinformation used to evaluate and predict safety, effectiveness, and value of treatments for each patients.
Rather than focusing on coverage decisions, CMS should focus on identifying opportunities and developing tools to improve clinical decision-making based on new science. The FDA has developed a Critical Path opportunities list in cooperation with many interested parties that provides 76 concrete examples of how new scientific discoveries—in fields such as genomics and proteomics, imaging, and bioinformatics—could be applied during medical product development to improve the accuracy of the tests used to predict the safety and efficacy of investigational medical products. CMS should begin the process of developing a similar list of ways new discoveries and tools such as electronic patient records could be used to improve the predictive and prospective nature of medicine.
As a first step, CMS could use the reopening of the ESA coverage decision as example for how to achieve a more targeted and patient-centered use of ESAs in chemotherapy. An opportunities list could be generated around this particular issue with continued coverage conditioned upon participation in Critical Path activities.
That puts Europe light years ahead of our CMS that has deemed it cost effective and safe to toss tons of seniors into the dark ages of blood transfusions. I wonder what Pharmalot and others who had predicted a tightening of EMEA guidelines will say? Ditto the fact that the EMEA also took a mature approach to Avandia. But that is a post for another day.
For now, it is clear that CMS over-reached using the wrong data to achieve an over-restrictive decision inconsistent with the emergence of patient-centric medicine. EMEA is moving in that direction. So is FDA. Both have Critical Path programs designed to integrate the tools and knowledge to promote patient variation into the development and use of new drugs. Why not a Critical Path for CMS to achieve the same goal in developing insights into the value of new treatments?
So here's my proposal for a Critical Path for Comparative Effectiveness for CMS. Comments and thoughts welcome.
CMS should initiate a Critical Path for comparative effectiveness much as the FDA developed a Critical Path for drug approval and development. “The Critical Path Initiative is FDA's effort to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured.†CMS needs to initiate in a manner that is as transparent and as collaborative as that undertaken by the FDA to promote a national effort to modernize the science information the evaluation of the value of treatments. Just as the key scientific insights guiding the FDA critical path are genetic variations and biomedical informatics that predict and inform individual responses to treatment, CMS needs to establish a process to incorporate knowledge and tools that personalize evidence of response in its decisions.
It should to the extent possible use coverage to evidence development, research grants and partnerships with industry, the FDA, NIH, the new Reagan-Udall Critical path institute to “ harness the potential of bioinformation used to evaluate and predict safety, effectiveness, and value of treatments for each patients.
Rather than focusing on coverage decisions, CMS should focus on identifying opportunities and developing tools to improve clinical decision-making based on new science. The FDA has developed a Critical Path opportunities list in cooperation with many interested parties that provides 76 concrete examples of how new scientific discoveries—in fields such as genomics and proteomics, imaging, and bioinformatics—could be applied during medical product development to improve the accuracy of the tests used to predict the safety and efficacy of investigational medical products. CMS should begin the process of developing a similar list of ways new discoveries and tools such as electronic patient records could be used to improve the predictive and prospective nature of medicine.
As a first step, CMS could use the reopening of the ESA coverage decision as example for how to achieve a more targeted and patient-centered use of ESAs in chemotherapy. An opportunities list could be generated around this particular issue with continued coverage conditioned upon participation in Critical Path activities.
It is getting hard to figure out what to panic about first: Lead in lipstick? Cough medicines for kids? The statin surge among adolescents? How about MRSA in the boysroom? Can anyone guess which is associated with more deaths: MRSA or influenza? The answer is (b) influenza with 36000 deaths a year with another 11000 deaths linked to respiratory infections linked to flu as well. MRSA, 85-90 percent which are hospital related and found among the elderly who are immunocompromised is linked to about 17000 deaths. Handwashing anyone?
Get your Halloween chills the old fashion way. In the meantime read CMPI Sr. Fellow Mark Siegel's calming piece on MRSA in today's NY Post. It's before the article on Joe Girardi.
http://www.nypost.com/seven/10312007/postopinion/opedcolumnists/rx_for_the_superbug.htm
Get your Halloween chills the old fashion way. In the meantime read CMPI Sr. Fellow Mark Siegel's calming piece on MRSA in today's NY Post. It's before the article on Joe Girardi.
http://www.nypost.com/seven/10312007/postopinion/opedcolumnists/rx_for_the_superbug.htm
There is a lot of consternation about the fact that Rudy's ad comparing prostate cancer care in the UK and the US had some musty numbers on survival rates. They were wrong numbers that five minutes on the Web could have solved. Hence the error detracts from but doesnt' change the fact that you are more likely to die and less likely to survive five years after being diagnosed in the UK than any other Western country. To suggest, as some have, that five year survival rates, are not predictive or not a marker of quality of care, is absurd. The fact is, as a recent article in the Lancet points out survival rates reflect increased screening but only to the extent that it leads to treatment. Screening without treatment would not translate into fewer cancer deaths, which it has at a faster rate in the US than anywhere else. Indeed, controlling for screening, the key variable for increased survival and declining death rates is access to new medicines.
Which is the point of Rudy's ad. And the point of this recent article in UK's Daily Telegraph:
I won't let Daddy die: Girl of six raises £4,000 for life-saving drugs the NHS won't provide
By LUCY LAING
" Faced with the prospect of losing her father to cancer, Chantelle Hill reacted a little differently to the average six-year-old.
Instead of letting the grown-ups deal with it, she decided to save him herself.
Now, she has raised more than £4,000 to buy the life-saving drugs David Hill needs after he was told they were not available to him on the Health Service. "
Apparently NICE and the NHS decided that Tarceva, the drug Chantelle will pay for, but NHS won't, was not "an effective use of NHS resources".
I know there will be some who read this post and bleat about how some people can't afford drugs because they don't have insurance. Good point. But what's the point of insurance of any kind if your six year daughter has to ask your neighbors for money to pay for a drug that extends your life and improves it's quality? Could it be that our health system, which needs work, is better and more compassionate in this regard?
http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=490001&in_page_id=1770
Which is the point of Rudy's ad. And the point of this recent article in UK's Daily Telegraph:
I won't let Daddy die: Girl of six raises £4,000 for life-saving drugs the NHS won't provide
By LUCY LAING
" Faced with the prospect of losing her father to cancer, Chantelle Hill reacted a little differently to the average six-year-old.
Instead of letting the grown-ups deal with it, she decided to save him herself.
Now, she has raised more than £4,000 to buy the life-saving drugs David Hill needs after he was told they were not available to him on the Health Service. "
Apparently NICE and the NHS decided that Tarceva, the drug Chantelle will pay for, but NHS won't, was not "an effective use of NHS resources".
I know there will be some who read this post and bleat about how some people can't afford drugs because they don't have insurance. Good point. But what's the point of insurance of any kind if your six year daughter has to ask your neighbors for money to pay for a drug that extends your life and improves it's quality? Could it be that our health system, which needs work, is better and more compassionate in this regard?
http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=490001&in_page_id=1770
Scott Gottlieb tells it like it is via this column in today's edition of The Wall Street Journal ...
Attack of the Superbugs
By SCOTT GOTTLIEB
One of the early morning television news shows recently staged a live feed from a suburban Maryland high-school. It was the latest to close after a student contracted a virulent and drug-resistant bacterium called methicillin-resistant staphylococcus aureus, or MRSA. Pronounced "mersa," it's become this season's equivalent of shark attacks, every day bringing new, terrifying reports, although the dangers of such bacteria are hardly new.
Researchers working at the Centers for Disease Control and Prevention reported this month that nearly 19,000 Americans died in 2005 from MRSA, and about 95,000 were infected. Doctors have been reporting for years that MRSA was cropping up with alarming frequency. The same is true for other bacteria. In Rochester, N.Y., doctors recently reported nine children stricken with a strain of the bacteria that causes ear infections -- streptococcus pneumonia -- that was resistant to all 18 antibiotics commonly used to treat the condition.
The real news isn't that these bugs exist, but how woefully unprepared we are to deal with them. As we make progress in fields like cancer, we are taking a U-turn on bacteria. Despite advances in drug development, the bugs have increased their IQ nearly as fast as research, outwitting our medicines. Efforts have turned to preventing bacterial spread and clamping down on antibiotic prescribing.
There's no question that poor hospital hygiene, overuse -- and sometimes misuse -- of antibiotics contribute to educating bugs at our expense. But preventative efforts alone won't solve our bacterial challenges. What we need most are better diagnostic tests and new medicines.
This is high-stakes science, but the pipeline isn't promising. Since 1998, just 10 new antibiotics have been approved by the the Food and Drug Administration, only two of which work in fundamentally new ways. Only 13 new antibiotics are in development inside big drug companies, compared to an average of 60 more than a decade ago. Since leaving the FDA this year as its deputy commissioner, I've advised a few biopharma firms making antibiotics and the venture investors supporting them. Regrettably, however, many big drug makers have followed the lead of Eli Lilly, a pharmaceutical company that once pioneered antibiotics, only to exit the business entirely.
The problem? There's not a lot of payoff for developing drugs aimed at infections. First, they last only days, or at most weeks, limiting sales. And the better the drug, the more likely doctors and hospitals are to keep it on the shelf as a last resort. Most hospitals require that doctors get special approval to prescribe the best new antibiotics. In that regard, what's good for public health isn't necessarily good for antibiotic development.
Capricious regulation is another problem, adding to uncertainty and, in turn, the cost of development. For drugs targeted to many common bacterial ailments, the FDA historically required so-called non-inferiority trials. This meant a new antibiotic needed to prove it was generally no worse than existing treatments in order to win regulatory approval. Otherwise, conducting trials to prove a new antibiotic was better than a sugar-pill placebo -- or superior to existing drugs -- would require huge trials and, in some cases, was simply unethical if it meant asking patients with potentially serious infections to risk treatment by placebo.
That changed just last year when a handful of FDA reviewers became miffed that companies would get drugs approved through these non-inferiority trials without proving the new drugs were better than older medicines, and then market the new drugs for broad upper respiratory indications. The reviewers brought their complaints to Congress, which has since leaned on the FDA, at one point asking the Government Accountability Office -- staffed with lawyers and policy analysts -- to opine on the nuanced scientific question of non-inferiority trial design. The political intrigue has pushed the FDA to raise its approval bar in some areas, jettisoning the non-inferiority approach for some ailments while leaving a mess of uncertainty for many others.
So how do we surmount these obstacles to get the drugs and diagnostic tests we need to stay ahead of aggressive bacteria like MRSA?
First, we need to recognize that developing drugs aimed at super bugs is not an ordinary pharmaceutical business, and requires unique incentives. If public-health policies compel doctors to hold the best new antibiotics in reserve, we need to compensate with incentives for developing those niche drugs.
One way would be to clarify the rules under the 1983 Orphan Drug Act to include drugs that target resistant bugs. That law provides special incentives for drugs that treat rare diseases, including patent protections and streamlined regulatory review. The FDA needs to create better opportunities for companies to target not only conditions -- such as pneumonia or skin infection -- but also specific bacteria, like multi-drug resistant staph.
The FDA's guidance on other aspects of antibiotic drug development is similarly murky due, in part, to fluid standards. Congress recently had to write into law a demand that the FDA produce guidance on antibiotics for acute exacerbations of chronic bronchitis and acute bacterial sinusitis (finally released yesterday). Merely issuing documents doesn't guarantee clarity, and one of the FDA's recent documents on an aspect of antibiotic development ran several pages, saying little.
The FDA should collaborate with the Infectious Disease Society of America (IDSA) to develop meaningful guidelines that provide clear pathways to new drug development. The IDSA's credible voice could also buttress the FDA against the maneuvering of a handful of staff who take their views to politicians when they lose internal scientific debates.
Finally, we badly need better tools for rapidly detecting resistant infections in blood, even screens for bacterial genes. Today it can sometimes take days to discover that a patient is infected with a resistant bug. If there were better diagnostics -- similar to the "rapid" strep test -- bacterial infections could be distinguished early and doctors could treat patients with confidence. Drug companies could also more easily develop drugs targeted to specific bugs, conducting clinical studies aimed at specific pathogens, and making sure the right patients got the right drug early in the course of their illness, when drugs can make the most difference.
But the diagnostics business has been a lower-margin affair for many years, steering product developers into other fields. There are complicated reasons for this, but Medicare has systematically tried to drive down prices for diagnostic tests, often refusing to pay for new tests altogether. In turn, the big companies that make the tests committed a fundamental mistake early on, by adopting a strategy of charging lower prices for the throw-away test kits and premium prices for the platforms they run on -- a reverse of the old razor-blade model.
The big diagnostic companies figured they would make most of their money off the platforms. They're regretting that now. The strategy may have worked if they had continued to innovate, but now many of the best ideas for new tests are coming out of small firms that have little ability to sell their own big platforms, and a hard time premium pricing diagnostic tests in a market conditioned by the big firms to expect cheap razor blades.
Most existing antibiotics are as old as the earth, screened out of nature where they resided, doing battle with bugs for centuries. We need to accelerate this evolution in our laboratories. Public policy mistakes are partly to blame for creating this inhospitable environment for new development, and it will take a concerted effort to improve it. The only sure way to stay ahead of bacterial evolution is by escalating this arms race.
Dr. Gottlieb, a practicing physician and resident fellow at the American Enterprise Institute, was previously a Deputy Commissioner of the Food and Drug Administration.
Attack of the Superbugs
By SCOTT GOTTLIEB
One of the early morning television news shows recently staged a live feed from a suburban Maryland high-school. It was the latest to close after a student contracted a virulent and drug-resistant bacterium called methicillin-resistant staphylococcus aureus, or MRSA. Pronounced "mersa," it's become this season's equivalent of shark attacks, every day bringing new, terrifying reports, although the dangers of such bacteria are hardly new.
Researchers working at the Centers for Disease Control and Prevention reported this month that nearly 19,000 Americans died in 2005 from MRSA, and about 95,000 were infected. Doctors have been reporting for years that MRSA was cropping up with alarming frequency. The same is true for other bacteria. In Rochester, N.Y., doctors recently reported nine children stricken with a strain of the bacteria that causes ear infections -- streptococcus pneumonia -- that was resistant to all 18 antibiotics commonly used to treat the condition.
The real news isn't that these bugs exist, but how woefully unprepared we are to deal with them. As we make progress in fields like cancer, we are taking a U-turn on bacteria. Despite advances in drug development, the bugs have increased their IQ nearly as fast as research, outwitting our medicines. Efforts have turned to preventing bacterial spread and clamping down on antibiotic prescribing.
There's no question that poor hospital hygiene, overuse -- and sometimes misuse -- of antibiotics contribute to educating bugs at our expense. But preventative efforts alone won't solve our bacterial challenges. What we need most are better diagnostic tests and new medicines.
This is high-stakes science, but the pipeline isn't promising. Since 1998, just 10 new antibiotics have been approved by the the Food and Drug Administration, only two of which work in fundamentally new ways. Only 13 new antibiotics are in development inside big drug companies, compared to an average of 60 more than a decade ago. Since leaving the FDA this year as its deputy commissioner, I've advised a few biopharma firms making antibiotics and the venture investors supporting them. Regrettably, however, many big drug makers have followed the lead of Eli Lilly, a pharmaceutical company that once pioneered antibiotics, only to exit the business entirely.
The problem? There's not a lot of payoff for developing drugs aimed at infections. First, they last only days, or at most weeks, limiting sales. And the better the drug, the more likely doctors and hospitals are to keep it on the shelf as a last resort. Most hospitals require that doctors get special approval to prescribe the best new antibiotics. In that regard, what's good for public health isn't necessarily good for antibiotic development.
Capricious regulation is another problem, adding to uncertainty and, in turn, the cost of development. For drugs targeted to many common bacterial ailments, the FDA historically required so-called non-inferiority trials. This meant a new antibiotic needed to prove it was generally no worse than existing treatments in order to win regulatory approval. Otherwise, conducting trials to prove a new antibiotic was better than a sugar-pill placebo -- or superior to existing drugs -- would require huge trials and, in some cases, was simply unethical if it meant asking patients with potentially serious infections to risk treatment by placebo.
That changed just last year when a handful of FDA reviewers became miffed that companies would get drugs approved through these non-inferiority trials without proving the new drugs were better than older medicines, and then market the new drugs for broad upper respiratory indications. The reviewers brought their complaints to Congress, which has since leaned on the FDA, at one point asking the Government Accountability Office -- staffed with lawyers and policy analysts -- to opine on the nuanced scientific question of non-inferiority trial design. The political intrigue has pushed the FDA to raise its approval bar in some areas, jettisoning the non-inferiority approach for some ailments while leaving a mess of uncertainty for many others.
So how do we surmount these obstacles to get the drugs and diagnostic tests we need to stay ahead of aggressive bacteria like MRSA?
First, we need to recognize that developing drugs aimed at super bugs is not an ordinary pharmaceutical business, and requires unique incentives. If public-health policies compel doctors to hold the best new antibiotics in reserve, we need to compensate with incentives for developing those niche drugs.
One way would be to clarify the rules under the 1983 Orphan Drug Act to include drugs that target resistant bugs. That law provides special incentives for drugs that treat rare diseases, including patent protections and streamlined regulatory review. The FDA needs to create better opportunities for companies to target not only conditions -- such as pneumonia or skin infection -- but also specific bacteria, like multi-drug resistant staph.
The FDA's guidance on other aspects of antibiotic drug development is similarly murky due, in part, to fluid standards. Congress recently had to write into law a demand that the FDA produce guidance on antibiotics for acute exacerbations of chronic bronchitis and acute bacterial sinusitis (finally released yesterday). Merely issuing documents doesn't guarantee clarity, and one of the FDA's recent documents on an aspect of antibiotic development ran several pages, saying little.
The FDA should collaborate with the Infectious Disease Society of America (IDSA) to develop meaningful guidelines that provide clear pathways to new drug development. The IDSA's credible voice could also buttress the FDA against the maneuvering of a handful of staff who take their views to politicians when they lose internal scientific debates.
Finally, we badly need better tools for rapidly detecting resistant infections in blood, even screens for bacterial genes. Today it can sometimes take days to discover that a patient is infected with a resistant bug. If there were better diagnostics -- similar to the "rapid" strep test -- bacterial infections could be distinguished early and doctors could treat patients with confidence. Drug companies could also more easily develop drugs targeted to specific bugs, conducting clinical studies aimed at specific pathogens, and making sure the right patients got the right drug early in the course of their illness, when drugs can make the most difference.
But the diagnostics business has been a lower-margin affair for many years, steering product developers into other fields. There are complicated reasons for this, but Medicare has systematically tried to drive down prices for diagnostic tests, often refusing to pay for new tests altogether. In turn, the big companies that make the tests committed a fundamental mistake early on, by adopting a strategy of charging lower prices for the throw-away test kits and premium prices for the platforms they run on -- a reverse of the old razor-blade model.
The big diagnostic companies figured they would make most of their money off the platforms. They're regretting that now. The strategy may have worked if they had continued to innovate, but now many of the best ideas for new tests are coming out of small firms that have little ability to sell their own big platforms, and a hard time premium pricing diagnostic tests in a market conditioned by the big firms to expect cheap razor blades.
Most existing antibiotics are as old as the earth, screened out of nature where they resided, doing battle with bugs for centuries. We need to accelerate this evolution in our laboratories. Public policy mistakes are partly to blame for creating this inhospitable environment for new development, and it will take a concerted effort to improve it. The only sure way to stay ahead of bacterial evolution is by escalating this arms race.
Dr. Gottlieb, a practicing physician and resident fellow at the American Enterprise Institute, was previously a Deputy Commissioner of the Food and Drug Administration.
The first thing that needs to be said about medical devices is that we should stop calling them medical devices. They are, in every sense, medical technology.
And technology, as we all know, is what makes the world go ‘round.
That being said, we must take medical technology as seriously as we do pharmaceuticals.
And, as the use of medical technology (from stents to scans) becomes ever more important and more pervasive, so too must we focus on safety.
But we must not fall into the false security of the Precautionary Principle which warns us to do nothing until we know everything. Why is this a bad idea? Because we can never “know everything.†And when it comes to FDA regulated products, be they drugs or devices or combination products – there will always be risk that comes along with benefit.
Can we do a better job regarding medical technology safety? Yes. Must we? Absolutely. Are we?
Here’s what Dan Schultz, director of CDRH had to say in today’s Wall Street Journal on that point:
"Are there ways to identify problems more quickly? I think the answer is yes. But if you require a clinical trial for every design change, what does that do to the ability of bringing new technologies to market?"
What, you mean there's no easy answer? Sorry Senator Grassley.
Here’s a link to the article:
http://online.wsj.com/article/SB119370397918375690.html?mod=hps_us_pageone
Vigilance must not supplant progress. They must advance together and learn from each other.
And technology, as we all know, is what makes the world go ‘round.
That being said, we must take medical technology as seriously as we do pharmaceuticals.
And, as the use of medical technology (from stents to scans) becomes ever more important and more pervasive, so too must we focus on safety.
But we must not fall into the false security of the Precautionary Principle which warns us to do nothing until we know everything. Why is this a bad idea? Because we can never “know everything.†And when it comes to FDA regulated products, be they drugs or devices or combination products – there will always be risk that comes along with benefit.
Can we do a better job regarding medical technology safety? Yes. Must we? Absolutely. Are we?
Here’s what Dan Schultz, director of CDRH had to say in today’s Wall Street Journal on that point:
"Are there ways to identify problems more quickly? I think the answer is yes. But if you require a clinical trial for every design change, what does that do to the ability of bringing new technologies to market?"
What, you mean there's no easy answer? Sorry Senator Grassley.
Here’s a link to the article:
http://online.wsj.com/article/SB119370397918375690.html?mod=hps_us_pageone
Vigilance must not supplant progress. They must advance together and learn from each other.
Seems as though John Edwards must have been absent during the law school lecture on the US Constitution – specifically the part that relates to Freedom of Speech. In a speech the other day he called for, among other things, mandatory FDA approval before drug companies launch major ad campaigns.
Must have tested well in focus groups.
Similar bloviation during debate over FDA reform was quickly dismissed because of some more educated members of Congress familiarity with the First Amendment.
But, as we all know, facts and reality have very little to do with Presidential campaigns.
Further proof of this was Senator Edwards’ remark that drug advertising misleads patients and drives up health care costs.
Neither of these statements is true. As to “misleads patients,†what DTC does do is send patients (aka – consumers) into the offices of their physicians were they have important dialogue about their health. In many of these DTC-initiated visits a previously undiagnosed condition is diagnosed. And earlier diagnosis and treatment decreases health care costs.
As to whether or not DTC increases the cost of medicines, consider this – when you compare the prices of medicines within a given therapeutic category along with their spending on DTC, there is no correlation. Also, when you compare the amount of money spent on DTC versus research and development – they don’t even have the same number of zeroes.
According to Edwards, "The excessive costs of prescription drugs are straining family budgets and contributing to runaway health care costs.â€
Another nice sound bite that belies the truth. Only 11.5% of the US health care spend is on pharmaceuticals – the same pharmaceuticals that keep people out of the hospital (over 30% of our health care expense). Proper medication keeps people healthy, at work, and paying taxes.
But that’s not as popular a sound bite in Iowa and New Hampshire (where Senator Edwards shared his comments with primary voters).
"With such aggressive and often misleading drug company marketing, it's too easy for advertising -- instead of doctors or proven results -- to influence families' health decisions," Edwards' campaign quoted him as saying.
Often misleading? Really? Does he even know about “fair balance†and “adequate provision?†Does he even know about the research that shows how few people actually even try to read various brief summaries?
Probably not. And that would explain why the “Edwards Plan†also calls for drug advertising to disclose more information about side effects and comparisons of drugs against placebos and alternatives.
Someone should ask him about this during the next candidate debate. (And speaking of “comparisons,†someone should also ask him about his understanding of comparative effectiveness.)
Further, the Edwards plan would institute a two-year delay on consumer advertising of all new drugs.
So, not only do we not really need Freedom of Speech – we also don’t need new and timely information about new and timely medicines.
Gevalt.
Must have tested well in focus groups.
Similar bloviation during debate over FDA reform was quickly dismissed because of some more educated members of Congress familiarity with the First Amendment.
But, as we all know, facts and reality have very little to do with Presidential campaigns.
Further proof of this was Senator Edwards’ remark that drug advertising misleads patients and drives up health care costs.
Neither of these statements is true. As to “misleads patients,†what DTC does do is send patients (aka – consumers) into the offices of their physicians were they have important dialogue about their health. In many of these DTC-initiated visits a previously undiagnosed condition is diagnosed. And earlier diagnosis and treatment decreases health care costs.
As to whether or not DTC increases the cost of medicines, consider this – when you compare the prices of medicines within a given therapeutic category along with their spending on DTC, there is no correlation. Also, when you compare the amount of money spent on DTC versus research and development – they don’t even have the same number of zeroes.
According to Edwards, "The excessive costs of prescription drugs are straining family budgets and contributing to runaway health care costs.â€
Another nice sound bite that belies the truth. Only 11.5% of the US health care spend is on pharmaceuticals – the same pharmaceuticals that keep people out of the hospital (over 30% of our health care expense). Proper medication keeps people healthy, at work, and paying taxes.
But that’s not as popular a sound bite in Iowa and New Hampshire (where Senator Edwards shared his comments with primary voters).
"With such aggressive and often misleading drug company marketing, it's too easy for advertising -- instead of doctors or proven results -- to influence families' health decisions," Edwards' campaign quoted him as saying.
Often misleading? Really? Does he even know about “fair balance†and “adequate provision?†Does he even know about the research that shows how few people actually even try to read various brief summaries?
Probably not. And that would explain why the “Edwards Plan†also calls for drug advertising to disclose more information about side effects and comparisons of drugs against placebos and alternatives.
Someone should ask him about this during the next candidate debate. (And speaking of “comparisons,†someone should also ask him about his understanding of comparative effectiveness.)
Further, the Edwards plan would institute a two-year delay on consumer advertising of all new drugs.
So, not only do we not really need Freedom of Speech – we also don’t need new and timely information about new and timely medicines.
Gevalt.
By now you will have heard about the most recent in a series of FDA leaks. I refer specifically to the Wall Street Journal's "people with knowledge of the matter" -- the matter at hand being Avandia.
I will not speak to the specifics of the leak -- I will not give illegal and unethical behavior one inch of additional space -- nor will I spend any time or energy playing the "I wonder who the leaker is?"game. (Not that I don't have my own suspicions.)
What I do want to address is the growing trend within the FDA of "leaking" internal discussions to the media in order to try to force the agency's hand. If "politicizing" the agency is bad (and it is -- very much so) than it is bad writ large. The ends does not justify the means.
The FDA is an organization of health care professionals. An organization of many. Organizations have hierarchies. And organizations have rules. And rules are meant to be followed. The alternative is chaos -- a state into which the agency mustn't spin. When rogue employees choose to take the law into their own hands -- even when they believe their position is the correct one -- bad things ensue and stakeholder trust erodes. And, yes, one stakeholder is the pharmaceutical industry. Another is the American citizen.
Anonymous leaks are not the acts of whistleblowers -- they are the acts of cowards.
An "FDA of One" is one very bad idea.
I will not speak to the specifics of the leak -- I will not give illegal and unethical behavior one inch of additional space -- nor will I spend any time or energy playing the "I wonder who the leaker is?"game. (Not that I don't have my own suspicions.)
What I do want to address is the growing trend within the FDA of "leaking" internal discussions to the media in order to try to force the agency's hand. If "politicizing" the agency is bad (and it is -- very much so) than it is bad writ large. The ends does not justify the means.
The FDA is an organization of health care professionals. An organization of many. Organizations have hierarchies. And organizations have rules. And rules are meant to be followed. The alternative is chaos -- a state into which the agency mustn't spin. When rogue employees choose to take the law into their own hands -- even when they believe their position is the correct one -- bad things ensue and stakeholder trust erodes. And, yes, one stakeholder is the pharmaceutical industry. Another is the American citizen.
Anonymous leaks are not the acts of whistleblowers -- they are the acts of cowards.
An "FDA of One" is one very bad idea.
Matt Herper and Robert Langreth have a good column about Lilly's hurry up and wait approach to releasing the results of a dosing study about prasugrel, which would not compete with but be an alternative to people who do not respond well to Plavix or aspirin.
Again, it's not the data so much as how it is presented to investors and the clinical community. The rules of the road have changed. People demand more data. And the genetic underpinnings that cause differences in drug response and dose response -- which is what at issue here -- are pretty much like open source software or operating systems.
I don't think anything nefarious is going on. If the science types have control of the process -- and Steve Paul who runs RD at Lilly is a straight shooter -- they are probably retooling and re-examining the data to see which dose works for which groups.
But that is not the end of the matter. Matt and Robert should know that Lilly is likely trying to figure how all this tailored treatment info pans out and whether or not -- in the safety uber alles environment -- even a drug that has diagnostic or gene-specific dosing limits ala warfarin could even get through the FDA these days.
Maybe Lilly is compiling a list of drug safety vigilantes it needs to hire as consultants to ensure they don't trash the drug to the trial attorneys and the media. Drug safety? More like a protection racket.
http://www.forbes.com/2007/10/25/pharmacuticals-prasugrel-lilly-biz-sci-cx_mh_1026lilly1.html?partner=alerts
Again, it's not the data so much as how it is presented to investors and the clinical community. The rules of the road have changed. People demand more data. And the genetic underpinnings that cause differences in drug response and dose response -- which is what at issue here -- are pretty much like open source software or operating systems.
I don't think anything nefarious is going on. If the science types have control of the process -- and Steve Paul who runs RD at Lilly is a straight shooter -- they are probably retooling and re-examining the data to see which dose works for which groups.
But that is not the end of the matter. Matt and Robert should know that Lilly is likely trying to figure how all this tailored treatment info pans out and whether or not -- in the safety uber alles environment -- even a drug that has diagnostic or gene-specific dosing limits ala warfarin could even get through the FDA these days.
Maybe Lilly is compiling a list of drug safety vigilantes it needs to hire as consultants to ensure they don't trash the drug to the trial attorneys and the media. Drug safety? More like a protection racket.
http://www.forbes.com/2007/10/25/pharmacuticals-prasugrel-lilly-biz-sci-cx_mh_1026lilly1.html?partner=alerts
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
