November 05th, 2016

THIS IS NOT ONLY HAPPENING NEAR THE BORDER OF CALIF----IT IS HAPPENING IN US CITIES DEEMED FOREIGN ECONOMIC ZONES---LIKE BALTIMORE
As we said---the goal of global Wall Street now is to expand those national health systems built by health industry fraud of our Federal Medicare and Medicaid Trusts is to profiteer via health insurance premiums now that they are mandated----and to continue to divert Medicare and Medicaid to expanding health corporations this time overseas. This is why the state private health systems are telling us it is cheaper----MORE AFFORDABLE ---if US patients go overseas for their health care even if they have to use Medicare funds to pay for the flight. It's cheaper to have cancer treatments in Utah then in Baltimore so they will fly a patient across country. They are building Foreign Economic Zone specialty health care corporations using this AFFORDABLE CARE ACT format.
Latino immigrant citizens are being sold that having access to gutted of funding Medicaid is fine for all the PAYROLL TAXES they have paid that should be getting them strong quality health care with access to hospital treatment but their 5% to the 1% are SHOW ME THE MONEY and sell all these bad policies as good for immigrant families. The same is being done in US cities to low-income families who are now losing access to ordinary hospital and disease vector health care while 1% Wall Street players are hawking dental and eye care....preventative care.
SOCIAL DEMOCRATS WITH BERNIE SANDERS KNOW REAL DEVELOPED NATION QUALITY HEALTH CARE AND THAT IS WHAT EXPANDED AND IMPROVED MEDICARE IS ABOUT....AND YES, THAT INCLUDES ALL THESE PREVENTATIVE CARE STRUCTURES. ALL ONE WORLD ONE GOVERNANCE FOREIGN ECONOMIC ZONES HAVE THIS SAME GUTTED OF FUNDING MEDICAID FOR ALL WITH FREE GLASSES AND FREE DENTAL CHECKUPS. AMERICANS NOW GETTING THE SAME THIRD WORLD ACCESS TO HEALTH CARE AS DEVELOPING NATIONS.

1% Wall Street is playing on the fact that our last generation of citizens under CLINTON/BUSH/OBAMA were denied all the strong health care we received through last century!

The allure of cheap doctors, drugs and dentists in Mexico



By Barrett Newkirk


This article was produced as a project for the 2016 California Fellowship, a program of the Center for Health Journalism at the USC Annenberg School for Communication and Journalism.


Dentist Marco I–iguez Raya looks over Palm Springs resident Vic Yepello's teeth to follow up on his root canal on Wednesday, May 25, 2016 in Los Algodones, Mexico.



For Californians living near the border, Mexico offers what the U.S. does not: Reliable health care at a cheaper price.

The Desert Sun
Friday, October 21, 2016

When Vic Yepello has a toothache he doesn't call any of the dentists listed in page after page of the phone book. He calls Mexico.
When the day of the appointment comes, he hops in his car and drives east, going far beyond any of the dental offices within a few miles of his Palm Springs home. He heads south and eventually farther east. About three hours and 165 miles later, he parks in a lot that costs him $6 a day and then walks the final 300 feet across the U.S.-Mexico border.
Yepello, a 70-year-old real-estate agent and cycling nut, has made the journey to Los Algodones four times in the last 15 months. The village, wedged up where Mexico meets California and Arizona, has earned the nickname "Molar City" by catering to thousands of foreigners a year -- mostly Americans — who come seeking deals on fillings, crowns and false teeth. While they're there, many also stock up on cheap prescription drugs and eyeglasses.


For an appointment last May, Yepello left home before 7 a.m. Including one pit stop on the way, he arrived in Los Algodones with plans to have his teeth cleaned, shop for glasses and buy some heavy-duty ibuprofen.
The trip was a follow-up to a root canal and a crown he had gotten six months earlier. Lately, a tooth above that dental work had begun to feel sore.


“So I’m just going to have them X-ray that, take a look and it and see if there’s something going on there,” Yepello said during the morning drive.
After a relatively brief stint in the exam chair, some time spent popping into the eyeglass shop and pharmacy, and a break for lunch in the village, he made it back home in time for dinner with his husband.
It's hard to say how many people make similar trips each year, but the number from California alone is easily in the hundreds of thousands if not millions. More than 6 million private vehicles (a number that excludes buses) entered Mexico from the U.S. in 2015, but border authorities aren't counting how many people in all of those cars and trucks are making the trip for medical reasons.
In Southern California, if people haven't gone to Mexico for health care, they probably know someone who has. People overburdened by the price of getting what's supposed to be some of the best health care in the world are willing to seek out options that would have seemed overly risky not long ago. And while more Americans now have health insurance than ever before, the high price of seeing a doctor, dentist or filling a prescription have not slowed the annual growth in the amount of money Americans spend on health care in foreign countries.


Joseph Woodman, the author of the medical tourism guide Patients Without Borders, estimated that 900,000 Americans left the country for medical care in 2013, but Woodman is not counting people traveling for prescription drugs, a big draw to Mexico. Another estimate for California only based on a 2001 survey put the number at 952,000 adults heading to Mexico annually for medical care, dental work and prescription drugs.
In the Coachella Valley, the nine-city region that includes Palm Springs, one in 10 adults, or more than 36,000 people traveled to Mexico in the previous year for health care and prescription drugs, according to a 2013 survey.
Americans are spending money every year on health care in foreign countries. In 2015, the total climbed to $1.8 billion, according to the federal Bureau of Economic Analysis, up from $585 million in 2006.
Many people who have gone say price was their motivating factor.
Ingrid Joyal, 69, of Sun City Palm Desert went to Mexico and paid $300 for porcelain crowns, a third of what she would have expected to pay at home.
Three years later, Joyal has no regrets.
“It hasn’t fallen out, and it’s fine,” she said.


A town built on medical tourism


Yepello hadn't considered Mexico for dental work until getting the suggestion from a trainer at his gym. His Medicare doesn't cover most dental work, and Yepello knew he couldn't afford more than $2,000 to bring relief to his increasingly sore mouth with a new crown and root canal.
The trainer gave him the name of a trusted dental office in Los Algodones. Yepello called and the woman on the phone said everything would cost $550.
“And my jaw just dropped. I couldn’t believe that it could be that little,” he said.



Palm Springs resident Victor Yepello makes a day trip to the Mexican border town of Los Algodones for a follow up on his root canal with his dentist on Wednesday, May 25, 2016.Making the journey alone each time has made Yepello an expert on where to park, where to walk across the border and how to navigate around the village. There's typically no wait to cross the border in either direction. Only once was he asked to show a passport, and even though it had expired, he was allowed to enter Mexico.
On the U.S. side of the border, the Quechan Tribe of American Indians runs a parking lot where short-term visitors can keep their cars while in Los Algodones. The lot can be crowded in the winter months when more people are making the trip, but on a Wednesday morning in May, Yepello had his pick of hundreds of spots.
The Quechan also run a casino and hotel off of nearby Interstate 8 that attracts people who need to stay overnight while visiting Los Algodones. Yepello has stayed there once, and while he thought the hotel was perfectly nice, anyone wanting decent food should drive a little further east to Yuma.


Los Algodones is a touristy border town styled on a medical theme. The buildings are old but brightly painted. Just across the border, pharmacies dominate every block. Mixed in are the eyeglass shops and souvenir stands. Men and women stand outside doorways hawking deals on pills. Sidewalk signs next to them list prices for Retin-A, Voltaren, Spiriva and other drugs that require a prescription in the U.S.
Medications that can be legally prescribed in the U.S. can be brought back from Mexico for personal use, but in some cases a prescription is needed for the drugs to be allowed over. U.S. Customs and Border Protection has highlighted the painkiller Tramadol and anti-anxiety drug Xanax as two medications commonly seen at the border that, because they are Schedule IV drugs, require prescriptions.
The law still allows U.S. residents without a prescription for those drugs to import no more than 50 doses.

The Food and Drug Administration cautions Americans against buying prescription drugs in foreign countries. Officials with the agency have said that in their experience, many drugs coming from foreign sources and claiming to be the same as U.S.-approved drugs are of unknown quality.
'It still does the job'
Before Yepello can compare prices on Mexican ibuprofen, he must sit in the dentist's chair. He walks the short distance from the border crossing to the dentist office and then into a narrow waiting room fitted with modern furniture. Beyond a reception window and doorway are the exam rooms. Mounted on the wall outside one is a small dry-erase board listing the morning's appointments and the names of the patients. One at 9 a.m., Yepello at 10:30, then another at 11:30.



Dentist Marco I–iguez Raya displays his dental certifications in an exam room on Wednesday, May 25, 2016 in Los Algodones, Mexico.The exam room equipment looks new but simpler than the padded chairs and machines seen in American dental offices. Instead of giving Yepello water from a tube inserted into his mouth, the dentist hands him a small plastic bottle of water. Lined up neatly on a counter top are a can of disinfectant spray, a jar of cotton swabs, scotch tape and a decorated metal can holding pens and a pair of scissors.
“Some of their equipment might be a little bit standard technology,” Yepello said. “But it still does the job.”
Dr. Marco Raya displays his dental degrees on the exam room wall, including one from the  Autonomous University of Baja California, a large public university.
Speaking in Spanish while his assistant translates, Raya said most of his patients find him through word of mouth. He said with so many dentists in the same town, the competition means he can't afford to achieve less than excellent results.
Yepello's experience has convinced him it's possible to get dental care in Mexico as good as what's found in the U.S. The risk of complications is no different, he said.
“If something went wrong, yea I’d have to get back in my car and go down there,” he said. “But again it gets down to the affordability of it all. I don’t have to borrow money. I don’t have to do anything. I can just go do it.”
Experiences vary
At least twice a month, Dr. Ayman Elraheb talks to one of his dental patients in the Palm Springs area who has decided to go with a Mexican dentist over him, or who recently made the trip. He estimated the loss his Coachella Valley practice sees from patients going to Mexico at around $100,000 every year.
Elraheb, who went to dental school in his native Egypt before moving to the U.S. and taking additional classes to get licensed here, said there’s no competing with Mexico on price but called the quality of work “unpredictable.”
He figured 20 percent of the work he sees done in Mexico isn’t up to U.S. standards, and he's often paid to fix it.
“If you really don’t care about the outcome, OK, you have nothing to lose,” he said. “But you’re not getting another set of teeth.”
From 2009 through 2014, Americans’ dental care costs rose 2.1 percent on average to $113.5 billion, or a per capita increase from $334 annually to $357. Insurance covered about $6 for every $10, leaving $4 for people to pay out-of-pocket, according to the Centers for Medicare and Medicaid Services, which tracks national health care spending.
Looking into the future, the agency is predicting that in 2025 the nation’s dental care will cost just under $200 billion, or $566 per capita.
Elraheb said his prices are a reflection of overhead costs with a little worked in for profit after his expenses are covered.
In a statement posted to its website, the California Dental Association says it understands the allure of cheaper dental care abroad before telling patients they should do their homework before getting any work done. Without highlighting specific destinations, the CDA suggests patients research infection controls and safety standards in the foreign country and their legal rights if something goes wrong. Questions to ask include: Can I get a refund if problems arise? Are the costs of any unplanned follow-ups covered? Does the dentist have malpractice insurance or is a civil lawsuit possible?
“CDA suggests that consumers considering this option proceed with caution and with a full understanding of the potential health, safety and legal risks,” the statement concludes.



Dentist Marco I–iguez Raya looks over Palm Springs resident Vic Yepello's teeth to follow up on his root canal on Wednesday, May 25, 2016 in Los Algodones Mexico.Patients interviewed said they knew they accepted some risk by choosing Mexico. If something were to go drastically wrong, they acknowledged filing a malpractice lawsuit in Mexico seemed like an almost impossible process.
Phil York of Rancho Mirage has spent months trying to correct some of the dental work he had done in Los Algodones. Over two trips there in 2015, a clinic gave York, 49, five crowns. His insurance company even agreed to reimburse him for half of the $870 total price. At home, York was prepared to pay up to $700 per crown even after his insurance helped.
“The dental group was very clean and very professional,” York said. “Obviously, the prep work was not very fun. Getting five crowns done at one time is not an experience I would recommend.”
York was told he would experience some pain and discomfort in his mouth for one or two weeks. But more than eight weeks later, he was still feeling pain he described as “pretty intense.”
York followed up with Dr. Elraheb, who performed X-rays and examined York’s bite before determining four of the five crowns likely needed to be replaced.
One crown was repaired soon after, and York is talking to his insurance company to see if they can help cover the other costs. He has not reached out to the Los Algodones clinic.
“It clearly states on their contract that for any complaints or difficulties, you must return to them. You have to give them an opportunity to fix it,” he said. “When it’s a few hundred miles away and means going outside of the country and all that jazz, it’s a lot easier said than done.”
Do your homework


Mexico encourages patients and doctors to resolve disputes outside of court by offering arbitration services through an agency within the Ministry of Health known as Conamed, or the National Commission of Medical Arbitration. A 2005 study funded by the agency found the system was well liked by doctors and complaint filers and that the arbitration process tends to be faster and cheaper than court. Still, many cases still wound up in court.
A 2010 study published in the Yale Journal of Health Policy, Law, and Ethics examined the legal options for U.S. residents seeking compensation for inadequate medical care in various foreign countries and found it’s often a struggle. Building a case in U.S. courts against foreign doctors or clinics poses logistical challenges, while going through foreign systems can lead to drawn out processes for limited compensation.
In Mexico, the arbitration system resulted in an average recovery of $4,800, an amount that would not satisfy most American patients, the report said.
“In short, U.S. patients traveling to Mexico for medical care should not assume that its legal or arbitration systems will provide satisfactory recourse,” the study found.


To avoid future arbitration or lawsuits, Americans should research their options before heading to Mexico, said Woodman of Patients Beyond Borders.
“There’s care out there in some 20 destinations around the world, including Mexico, that’s as good or better than in the United States, but you got to look for it,” he said. “You’ve got to do your homework, and that’s especially true for the border towns and resort towns.”
In Woodman’s experience, half of the travelers think it is more important to research the doctor’s credentials while the other half will research the hospital or clinic. He recommended looking up international accreditation  and paying attention to legal claims. Reviews on sites like Yelp can steer people toward quality, but only if there's a long history of positive feedback.
Any place that doesn’t respond to emails within 40 hours is giving you a warning sign to look elsewhere, he said.
“If they don’t feel good when they get there, they can always back out,” he said. “They don’t have to sign those admission papers.”


Yepello has now made four trips to Los Algodones, and his husband is considering going for new glasses. His Facebook posts about his experience have prompted at least two of his friends to go.
Part of the glowing review he wrote online immediately after returning from that first trip summed up his feelings. “Our system here is so broken...... this is really a no brainer."
[This story was originally published by The Desert Sun.]

__________________________________________Indeed, Hillary will fight for Affordable CAre Act---it is the far-right 1% Wall Street global health policy!
Below we see the Bill Gates global PHARMA corporation executive Burwell installed by Obama to Health and Human Services to carry on these global privatized health policies. When she says that by 2020----there is that same goal playing from this economic crash and installation of Trans Pacific Trade Pact------75% of Medicare will no longer be FEE FOR SERVICE.
THIS IS THE GUTTED OF FUNDING MEDICAID FOR ALL----AND ALTHOUGH IT MAY HIT ONLY 75% OF AMERICANS BY 2020----90% OF AMERICANS WILL BE PUSHED TO THIS PREVENTATIVE CARE ONLY OVER THE COMING DECADE OR TWO.
Why are global 1% Wall Street PRETENDING fee for service is bad when it is CAPITALISM? It is not going away it is simply removing Americans from what they always understood health care to be---FEE FOR SERVICE. They are simply creating block granted health structures as we have in Baltimore where 90% of citizens are sent to charity ----non-profit------NGO kinds of health access----while a 10% of Americans are soaked trying to pay rising private insurance premiums allowing them to continue with what is ordinary US health care. Remember, Affordable Health Care means keeping human capital able to work as cheaply as possible---it has nothing to do with lowering costs for quality health care.
1% Wall Street calls this network of NGOs and charity ----PUBLIC OPTION----it has nothing to do with our Federal public Medicare and Medicaid----it is totally deregulated---no oversight and accountability ---filled with pay-to-play and corruption----with no tracking of health care outcomes----THIS IS BALTIMORE'S PUBLIC HEALTH STRUCTURE GOING GLOBAL.
*
As president, Hillary will:
Defend and expand the Affordable Care Act, which covers 20 million people.
Hillary will stand up to Republican-led attacks on this landmark law—and build on its success to bring the promise of affordable health care to more people and make a “public option” possible. She will also support letting people over 55 years old buy into Medicare.
'Perhaps the most important thing Burwell could do is to declare a specific goal for payment reform -- I favor aiming to have 75 percent of Medicare costs paid in some way other than fee-for-service by 2020 '

Orzag is a Brookings Institution Wall Street neo-liberal economist speaking policy pushed by global Wall Street----Burwell is the global 2% now in charge of our Federal public health working to maximize profits for Bill Gates and the global health industry-----and Hillary has of course pushed global neo-liberal health system development in Foreign Economic Zones overseas for 3 decades....they are simply bringing what was installed overseas in developing nations back to the US---replacing our best in the world public health access.

Corralling health costs means----we don't need 90% of Americans accessing hospital and disease vector treatments----let them have preventative only


Will Burwell Corral Health-Care Costs?
April 14, 2014 11:53 AM EDT
By
Peter R. Orszag


In the past several months, health-care costs outside Medicare may have accelerated, even as Medicare spending growth remains remarkably low. This is why Sylvia Mathews Burwell (who is a friend of mine) has the opportunity to be a transformational secretary of Health and Human Services. If over the next three years she can take the bold steps needed to reinforce better value in health care, she will drastically alter prospects for everything from the federal budget to state and local priorities (including education) and the take-home pay of America's workers.


After several years of very slow growth, total health-care spending picked up in the fourth quarter of 2013, data from the Bureau of Economic Analysis show. This has led some commentators to declare an end to the era of slower health-cost increases, which has lasted for the past several years. Yet Medicare spending growth is still low, even through last month. Indeed, in the first half of this fiscal year, nominal Medicare spending was only 0.6 percent higher than in the corresponding period a year earlier.


The combined acceleration in total health-care spending (which should be expected to pick up as the economy continues to recover) and continued low growth in Medicare highlights why leadership is needed from Health and Human Services. If the secretary provides a clear glide path for shifting away from fee-for-service payments, then low health-cost increases will be much more likely.


Perhaps the most important thing Burwell could do is to declare a specific goal for payment reform -- I favor aiming to have 75 percent of Medicare costs paid in some way other than fee-for-service by 2020 -- and then lay out a timetable for how to get there. Such clarity is crucial because health-care providers already anticipate a shift toward value-based payment mechanisms and are poised to respond, but the timing is unclear, as is exactly which new payment model will prevail. This ambiguity impedes strategic planning and action.
With a better sense of how they will be paid for value rather than quantity, providers could do much to limit cost growth -- as demonstrated by the results from the many new payment systems (such as the Alternative Quality Contract in Massachusetts) currently being tested. Lower cost growth, in turn, would have multiple benefits, as a series of paperspresented at the Brookings Institution last week illustrate.
Two of these reports examined what would happen if health-care costs grow a) at the same rate as income per person or b) 2.5 percentage points faster. Economists Alan Auerbach of Berkeley and William Gale and Benjamin Harris of Brookings foundthat, under the lower-growth scenario, stabilizing the federal debt between now and 2040 would require tax and spending changes amounting to 1.3 percent of gross domestic product -- a challenge, but a manageable one.
Under the higher health-spending scenario, in contrast, immediate tax increases or spending cuts equal to a whopping 4 percent of GDP would be needed to stabilize debt as a share of the economy through 2040. Over longer periods, the differences are even greater; under the more rapid spending scenario, no plausible traditional tax increases or spending reductions would be sufficient to stabilize our fiscal trajectory.
As for state and local governments, the low-growth scenario is "unlikely to pose particularly difficult decisions," Donald Boyd, a fellow at the Rockefeller Institute of Government, found. But high growth would impose severe stress: Over the next two decades, state and local governments would have to either cut all nonhealth spending by 20 percent or increase taxes to a level 20 percent higher than they have been in 70 years, as a share of GDP.
Clearly, much is riding on whether we can improve value and maintain low cost growth in health care. Sylvia Burwell, an inspired choice to be the next secretary of Health and Human Services, has the opportunity to boldly lead the system toward a brighter future in which our dollars buy better health care, not just more of it.
(Peter Orszag is vice chairman of corporate and investment banking and chairman of the financial strategy and solutions group at Citigroup Inc. and a former director of the Office of Management and Budget in the Barack Obama administration.)

____________________________________________
Here is Hillary doing the far-right 1% Wall Street deregulation of our once strongly regulated and safe health care system making it sound like she is SOCIALLY PROGRESSIVE IN HELPING AMERICANS ACCESS MORE MEDICAL INNOVATIVE PRODUCTS by breaking down any FDA-----Department of AG----Clinical Trial/IRB/patient safety procedures that keep medical patent mills from rolling out any old product with the idea that if it is harmful-----some millions of people will be harmed or die----but that product patent will bring billions of dollars to a health industry corporation before it has to be taken from the market.
These few decades of CLINTON/BUSH/OBAMA has seen medical research done overseas in Foreign Economic Zones just for this purpose----they have been skirting all US regulations and laws surrounding patient and public health safety. Now global 1% Wall Street expects --when bringing foreign medical corporations to US city Foreign Economic Zones ----to operate the same way.
THAT IS WHAT HILLARY IS SAYING HERE! DOES WHAT SHE SAYS SOUND ANYTHING LIKE THIS GOAL? OF COURSE NOT---SHE IS PROGRESSIVE POSING.
What she is saying is more and more and more of what used to be actual health care access funding will now go to MEDICAL PATENT MILLS----THE BIOTECH FACILITIES TIED TO GLOBAL CORPORATE CAMPUS UNIVERSITIES. What used to be Americans going to a hospital for cancer treatments is now NO CANCER TREATMENTS but all that money once spent giving that American citizen those cancer treatments will now fund
INNOVATIVE NEW PATENT MILL MEDICAL PRODUCTS----DESIGNER MEDICINE DOES NOT INCLUDE THE 99%.
“Over the past year, we’ve seen far too many examples of drug companies raising prices excessively for long-standing, life-saving treatments with little or no new innovation or R&D,” Clinton said. “It’s time to move beyond talking about these price hikes and start acting to address them. All Americans deserve full access to the medications they need — without being burdened by excessive, unjustified costs. Our pharmaceutical and biotech industries are an incredible source of American innovation and revolutionary treatments for debilitating diseases. But I’m ready to hold drug companies accountable when they try to put profits ahead of patients, instead of back into research and innovation.”


Republicans have been trying for a century to end all those pesky New Deal public health protections built into our FDA and Department of AG-----these are simply steps to make that skirting of law official-----neo-conservative states and cities like Texas and Baltimore have been doing this these few decades -----this is why medical lawsuits have soared-----people dying from ordinary hospital stays and taking ordinary prescription PHARMA.



Table of Contents
Volume XXI Issue 2, Winter 2005
« Cartoon

A New System for Moving Drugs to Market
by Raymond L. Woosley, Glenn Rice



Today’s system for developing and approving drugs is fundamentally flawed. Fixing it will require new technological tools and new regulatory approaches.


The pharmaceutical industry is one of the most successful components of the U.S. economy. In recent years, however, critics have increasingly blamed the industry for setting prices too high, for earning too much profit, and for developing more “me too” drugs than truly innovative therapies. High prices have led private citizens, organizations, municipalities, and states to purchase prescription drugs from Canada, and they have prompted Congress to consider legalizing the reimportation of drugs, a serious threat to the future viability of the industry.


The industry justifies its product prices in several ways. First, the industry points out that its R&D costs are enormous. Its trade organization, the Pharmaceutical Research and Manufacturers of America, estimates that bringing the average drug to market costs more than $800 million. Second, the industry says that getting a new drug to market takes a long time, typically 12 years to 15 years, which leaves companies with only 2 to 5 years of patent life remaining before competition from generic drugs begins. Thus, the initial return on investment and the bulk of profits must be made during a relatively short period; profits that in turn are used to fund more R&D. These factors are often cited as pushing companies to invest mainly in drugs that have a good chance of success (that is, drugs in a therapeutic class that already has demonstrated clinical value and large profit potential) rather than to explore untested therapeutic areas.


Where the industry sees good business sense, however, we see fundamental flaws in the process by which drugs are developed. Moreover, these problems are due, in large measure, to flaws in how the federal government currently regulates drug development and the introduction of new drugs into the market.
Today’s drug development process, which has come to be characterized by high costs and slow output, has evolved during the past 50 years. The process is built on the best of intentions: providing the highest standards for assessing the efficacy and safety of drugs. But it is not appropriately structured for the way drugs are marketed and used today. Its framework rests on the principle that the U.S. Food and Drug Administration (FDA) should require drug companies to conduct the entire scope of work necessary to establish the absolute safety and efficacy of a drug before it is marketed. In practice, however, this approach has not always worked and is inconsistent with our current understanding of the biologic diversity of humans. Experience has shown that some investigational drugs that appeared safe and effective before they were approved turned out to have unacceptable toxicity after they reached the market and were used by millions of people.


The framework also relies on the principle that providing warnings about a drug’s potential risks, either by printing such warnings on the product label or in package inserts, will protect people from being harmed. But here again, experience has shown otherwise. Consider three prescription drugs once in common use: Seldane, Hismanal, and Propulsid. Each carried warnings on their product labels that they should not be taken along with certain other drugs, such as erythromycin, because the combination could trigger life-threatening arrhythmias. But some health care providers either did not read the warnings or ignored them, and many patients died as a result. The manufacturers finally removed the drugs from the mass market. Consider another three widely prescribed drugs that were known to carry a risk of liver toxicity: Rezulin, Duracet, and Trovafloxacin. All were removed from the open market because physicians were failing to adhere to warning labels indicating that patients should have their liver functions monitored during therapy. The drugs, when used as directed on the label, were considered safe.


R&D up; drugs down


FDA has now identified problems with the drug development process. In March 2004, the agency issued a white paper, Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products, which concludes that there is stagnation in the development process. Known as the Critical Path report, it declares that the drug pipeline, as measured by the number of applications submitted to the FDA for new medical therapies, is not growing in proportion to the national investment in pharmaceutical R&D.


The national investment comprises three parts: pharmaceutical industry investment, National Institutes of Health (NIH) investment, and venture investment. Industry and the NIH account for the lion’s share. Both sectors have increased their investments dramatically in recent years, with their combined totals rising from roughly $30 billion in 1998 to nearly $60 billion in 2003. (This total is expected to top $60 billion in 2004.) The NIH budget for research has doubled during this period, while industry expenditures for R&D have risen 250 percent during the past 10 years. However, venture investment has not kept pace and has even declined during the past four years, for reasons that will soon become apparent.


In light of such large investments, many people expected to see a host of exciting new treatments for human illness emerge. But the number of applications to the FDA for new chemical drugs has not changed, and the number of applications for new biological drugs has actually declined. Some observers have blamed this shortfall on a slow review of applications by the FDA. But this is not the case. Since Congress authorized the FDA to charge a “user fee” in the early 1990s, the agency has been able to hire more staff to review applications and has cleared the backlog that had accumulated. Review times now stand at an average of eight months for important new drugs.


Further evidence also points to problems in the drug development process. Despite a host of technological and scientific advances in such areas as drug discovery, imaging, genome sequencing, biomarkers, and nanotechnology, failure rates in drug development have increased. In fact, new drugs entering early clinical development today have only an 8 percent chance of reaching the market, compared with a 14 percent chance 15 years ago. In addition, failure rates during final clinical development are now as high as 50 percent, compared to 20 percent a decade ago.


The long, expensive, and risky development process helps explains the declining investment by the venture sector. Venture capitalists typically invest in smaller companies. But smaller drug companies cannot promise returns on investment for a decade or more, and this feature makes them less attractive as investment opportunities. Problems are greatest for companies working on drugs for small medical markets, because most large pharmaceutical companies typically will license products from venture firms only when those products have a market potential of at least half a billion dollars. Thus, many companies are left to fail, which discourages further investment in new drugs.


Promoting partnerships


The FDA’s Critical Path report calls for innovations to speed the development of new drugs, with the agency declaring: “We must modernize the critical development path that leads from scientific discovery to the patient.” Modernization, the report adds, will require conducting research to develop a new product development toolkit. This kit should contain, among other things, powerful new scientific and technical methods, such as animal- or computer-based predictive models, biomarkers for safety and effectiveness, and new clinical evaluation techniques, to improve predictability and efficiency along the path from laboratory concept to commercial product. Toward such goals, the FDA has invited the pharmaceutical industry and academia to join with the agency in conducting research that will provide “patients with more timely, affordable, and predictable access to new therapies.”


This idea is not without precedent. As early as the 1980s, the FDA began working closely with the pharmaceutical industry on innovative ways to develop new drugs for HIV and AIDS. These efforts resulted in average development times as short as 2 to 3 years, while the average for all drugs was growing to 12 years. This experience clearly demonstrates the feasibility of accelerating drug development without taking dangerous shortcuts. In fact, if drug developers are thoroughly innovative, accelerated drug development could be more informative than the current process and lead to greater understanding of the safety and effectiveness of marketed drugs.


To make the early release of a drug rational, it will be essential to have an intensive plan for postmarketing safety assessment and risk management.
The FDA also has joined in partnership with the food industry and the University of Illinois to create the Center for Food Safety Technology, and with the industry and the University of Maryland to create the Joint Institute for Food Safety and Nutrition. Based at the respective universities, these centers are intended to serve as neutral ground where the partners can participate in research of common value to the food industry and the public. Today, the FDA and SRI International (formerly Stanford Research Institute) are joining with the University of Arizona in developing the first partnership aimed specifically at accelerating the development of new drugs by creating the innovative tools called for in the Critical Path report. The new Critical Path to Accelerate Therapies Institute, or C-PATH Institute, will serve as a forum where the partners can discuss how to shorten drug development times without increasing the risk of harm to patients, and then set about bringing these plans to fruition.


Fast—and safe


How will safety be addressed when drug development is accelerated? The answer may not be one that many people expect.
Recent experiences with drugs that were found to cause serious adverse events after they had entered the market, such as Vioxx, which was linked to cardiovascular problems, have convinced many people that a major weakness in the current system is its failure to adequately assess safety before drugs are marketed. In the past eight years, 16 drugs have been removed from the market. Were these drugs inadequately tested? Not by current standards. Today, more is known about a new drug reaching the market than was known about any previously approved drug in its class. However, the current drug development system mistakenly assumes that drug safety can be adequately ascertained during development.


To better explain, it is first necessary to look at the drug development process. After a prototypical new drug spends several years in the discovery process and preclinical testing, it enters the first of three phases of clinical development. Phase I is intended to determine how well humans tolerate the drug and whether it is generally safe. The drug is given to volunteers in single doses, beginning at low dosages and increasing to higher dosages, and then in multiple doses. Most companies choose to use healthy volunteers in these trials, because this approach is easier and far less expensive than enrolling patients with the target illness, and the trials typically include only a few dozen people. Such constraints limit the amount of information that can be gained in this phase.


Phase II is conducted in patients with the target indication. This phase often lasts one to three years and involves a few hundred patients. Doses are increased over the anticipated clinical range, and the trials provide the first substantial evidence of pharmacologic activity and demonstrate that the drug has the desired efficacy. The trials are followed by an “end of phase II” meeting between FDA reviewers and representatives of the sponsoring company, in which the parties agree on a tentative plan for phase III trials. The conundrum that the FDA reviewers face is deciding how much more safety data they should require be obtained in phase III, recognizing that every requirement they impose further delays patient access to what may be a valuable new therapy.


Phase III often lasts 8 to 10 years and involves 1,000 to 3,000 patients. The trials serve as a proof of concept, in which patients are treated under conditions that more closely resemble the real world of clinical medicine. Data are examined to be sure that the drug will continue to demonstrate the type of efficacy observed in phase II and maintain an acceptable safety profile. The FDA’s goal is to determine whether the drug’s benefits outweigh any known or suspected risks. In recent years, this also has become the phase in which the company is expected to verify the possible consequences of drug interactions and determine whether dosage adjustments will be required in patients with concomitant diseases, such as renal failure, liver disease, and heart failure.


If all goes well in phase III, the FDA approves the drug and it enters the marketplace, often in a major way. With today’s aggressive marketing and direct-to-consumer advertising, new drugs frequently are being taken by millions of people early after launch, often in ways not anticipated during development or intended in the labeling. This sudden increase in usage leaves little time for the FDA and the manufacturer to detect any serious medical risks that might arise before the number of people affected has grown quite high.


And when millions are exposed, risks are almost certain to arise. The current drug approval system assumes that safety can be adequately ascertained during clinical trials that typically test a drug on several thousand people at most. This is simply not a valid assumption, because of the biologic diversity that exists in humans and the fact that marketed drugs are not always used in the same way as when they were being developed. The types of adverse reactions that result in drugs being removed from the market occur at a rate of less than 1 per 10,000 patients treated. Only if the investigational database for a new drug included more than 30,000 people could such rare events have a 95 percent chance of being detected before approval. No drug company could afford to conduct development programs of such magnitude. Asking companies to increase their investment in phase III without addressing the flaws that exist in the overall development process will only further delay development and increase the price of drugs. Furthermore, doing so is unlikely to detect adverse events that are relatively rare.

THIS IS WHY PUBLIC HEALTH HAS NOT BEEN IN THE PRIVATE SECTOR-----IT IS NOT CONDUCIVE TO COST AND PROFIT.  WE HAVE OVER A CENTURY HAD MUCH OF OUR MEDICAL RESEARCH AND PHARMA CONDUCTED AT PUBLIC RESEARCH UNIVERSITIES WHERE COST AND TIME TAKEN IS NOT A FACTOR.  WITH NO PATENTING OR PROFIT THESE PUBLIC HEALTH RESEARCH CAME TO CITIZENS LOW COST.


Further, even when adverse events are recognized and the FDA issues warnings, the lack of response by many health care providers often fails to effectively limit the harm. This means that the FDA’s only realistic option is to request that the drug be removed from the market. There also have been recent examples in which investigational drugs (ximelagatran and sorivudine) that demonstrated adverse events due to drug interactions during clinical trials were not approved by the FDA because the agency could not be assured that the manufacturer would be able to effectively manage the risk once the drugs were on the market.


Blueprint for action


What is needed is an alternative approach to developing and regulating new drugs. We propose a system that provides earlier approval for new prescription drugs, but requires more gradual growth in their use and comprehensive assessment of their safety as they spread through the marketplace. These changes will allow time for more complete real-world safety testing and for assimilating drugs into the daily practicie of medicine before millions of people are exposed to them.


The first change suggested is in phase II clinical trials. The trials would be expanded to include more complete characterization of the drug’s dose-response relationship in the intended population and subpopulations (for example, the very elderly, people with renal insufficiency, and people with co-morbid conditions) and to include more thorough drug interaction studies. Such studies would make use of modern computing techniques, biomarkers, adaptive trial design, and other advanced tools as suggested in the Critical Path report. Trials typically would take about four years, at which time the drug could be approved for marketing to a carefully defined population of patients. This approach is similar to the way in which several AIDS drugs, such as the protease inhibitors, were developed and translated into clinical practice in two to four years.


To make the early release of a drug rational, it will be essential to have an intensive plan for post-marketing safety assessment and risk management. Here, academic groups may have an important role to play. Groups such as the Centers for Education and Research on Therapeutics (CERTs), funded by the Agency for Healthcare Research and Quality, can develop risk management programs and conduct outcomes research on large databases and registries to confirm the efficacy and safety predicted from phase II trials. The groups also can use similar methods to confirm efficacy and evaluate the potential efficacy of the drug in new indications. This would be a very appropriate use of the CERTs, whose congressional authorization includes the mandate to improve the outcome from prescription drugs and other therapeutics.



These changes will allow time for more complete safety testing and for assimilating drugs into daily practice of medicine before millions of people are exposed to them.


In most cases, newly approved drugs should be given to a defined population under observed conditions, perhaps in a manner similar to that used in the “yellow card” system in the United Kingdom, in which physicians report the outcome of therapy (on a yellow card, of course) in each patient receiving a specific drug. Indeed, modern electronic medical record systems available in many health care delivery systems should make it possible to track the outcome of every treated patient in that system. The FDA and the pharmaceutical manufacturer would have to employ measures to assure that the drug is initially used as directed in labeling. Manufacturers could be encouraged to follow the lead of at least one innovative company that pays commissions to sales representatives based on how well doctors in their region use the company’s drug instead of how often the drug is prescribed.


This system would enable a company to begin marketing a new product earlier, with less total capital investment, and at a time when much more of the drug’s patent life is still in effect. The system also should make it possible to detect any serious life-threatening problems earlier, and certainly before millions of people have been exposed. In addition, for companies using this track, serious consideration should be given to offering indemnification from lawsuits filed for adverse events in return for the company paying for any medical expenses resulting from such adverse reactions. This would provide drug companies and patients alike with some relief from the harm caused by a new drug and would recognize the inevitable nature of adverse drug reactions.


After a period of careful observation, drugs that appear safe and effective could be approved for expanded markets, with fewer or no restrictions on their use. This situation would effectively be the same as the current market in which licensed physicians can prescribe a marketed drug for any indication, as long as the physician has evidence that such use has a scientific basis. If a marketed prescription drug is found to be relatively safe and used for a condition that can be self-diagnosed by the patient, it has been customary for it to be given nonprescription or “over-the-counter” (OTC) status. But this is a significant change in status and therefore poses a difficult challenge for regulators. Canada and many other countries have introduced an intermediate status that allows for a more gradual transition. These countries often move from prescription-only to “behind-the-counter” status, in which a patient must ask the pharmacist for the drug. The pharmacist can then perform prescreening or counseling that could make it more likely that the drug will be used safely. This additional step could widen the therapeutic benefit to patients, better utilize the important role of pharmacists, and minimize the risk of therapy. After a period of safe use in this status, a drug may be recommended for full OTC status when justified.
Unfortunately, many people in the pharmaceutical industry and the FDA may be reluctant to change the system that has evolved. But in today’s rapidly changing scientific environment, the current rigid and unidimensional system does not well serve the FDA, industry, patients, or society. Not only must the FDA be given a better opportunity to protect the public from unsafe drugs, but it must be given the tools to expedite the availability of new therapies. This process must be transparent and take place in an environment of openness, risk sharing, and scientific excellence that is in the best interest of everyone. Only in this way can the FDA become a full partner in developing the critical path for new drug approvals.

Recommended reading
Food and Drug Administration, Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products (Washington, D.C.: FDA, March 2004).
______________________________________

I attended what has been the corporatization of Maryland's and Baltimore's university research facilities MOVING FORWARD with deregulation of any remaining protections that require medical devices, PHARMA, and medical procedures to have been taken through clinical trials mitigating harm to citizens. What Baltimore has installed BYPASSES what used to be IRB Board approvals-----Patient's Bill of Rights in being brought into research projects----and FDA approvals already subprimed are now being completely dismantled. So, any research project Johns Hopkins via its BIOTECH FACILITY that Wall Street investment firms or global corporations want to fund-----can be moved forward with no public interest oversight. The only factor in these deals is whether that product will bring profits. Hopkins has been doing this these few decades especially overseas----Obama and Clinton neo-liberals are using the Affordable Care Act to say---WE NEED TO END REGULATIONS AND FDA INTERFERENCE IN BRINGING INNOVATIVE MEDICAL PATENTS TO MARKET IN THE US. Global health corporations had no public interest regulations or patient protections when working overseas these few decades----so they do not want them while working in the US----

We have growing public health problems just from citizens being brought into all this profit-driven medical research----the executives at what are now private global health corporation research facilities CATEGORIZED AS NON-PROFIT BECAUSE THEY ARE STILL CALLING THESE FACILITIES UNIVERSITIES-----are not HIPPOCRATIC OATH kinds of people----they are driven by profits that can come from patented products.


 Many citizens in Baltimore exposed to these research projects having no oversight and accountability have been made afraid to access ordinary health care suspecting UNETHICAL TREATMENT.


 This is what Trans Pacific Trade Pact policy in health care does---it makes it impossible for a nation to install FDA or any kind of public protections in health products because it hinders profit for those global health corporations. Hillary/Trump are TPP-----no matter how much HILLARY LIES!

A Trap for the Wary: How Compliance with FDA Medical Device Regulations Can Jeopardize Patent Rights

IDEA—The Intellectual Property Law Review
July 2006Raciti, Eric P.ArticleShare

Authored by James D. Clements and Eric P. Raciti


Abstract

The medical device industry is unique in its highly regulated nature, generally short R&D cycles, and growing financial incentives. Patent protec-tion, both in the USA and abroad, is critical for medical device companies to survive competition, protect its market space, and attract investment. Medical device companies are also subject to FDA regulations, which place conditions on the sale of medical devices. In certain circumstances, the interplay of the patent and medical regulatory systems in the USA can serve to destroy the patent rights of a compliant, but unwary, medical device company.




I. Introduction



The medical device industry is unique in several respects. One major distinction is its highly regulated nature, especially in lucrative technologies related to invasive surgical procedures. While it might appear that the medical device industry shares an analogous regulatory framework (and the same regulatory agency, the U.S. Food and Drug Administration (hereinafter "FDA")) with the pharmaceutical industry, the complexity, clinical burden, and time for regulatory permission1 to enter the market are usually far less onerous for medical devices. This translates to much shorter product times-to-market, and a more kinetic competitive environment. The added financial incentives in this industry, which show no signs of abating, place a premium on the market exclusivity that a patent estate can provide.     


The regulatory function of the FDA is to ensure the welfare of the public by requiring that the safety and efficacy of medical devices are, to the largest extent possible, documented and scientifically established before a device enters the stream of commerce. A corollary function of the FDA is to ensure that the public is made aware of any dangers or risks that accompany the use of a particular device already on the market. While the filings made by a company for premarket regulatory purposes are held in confidence until permission is granted, the same is not true for obligatory reports made to the FDA about adverse events involving a device's safety or efficacy. As an additional matter, the duty to report adverse events is sometimes incumbent on entities or persons not directly under the control of the company.  


The patent laws are a separate regulatory framework that results for the successful applicant, in limited monopoly rights for inventions. Inventions are, by definition, both novel and non-obvious over what is already known ("prior art").  Generally speaking, an applicant for a patent is under pains to avoid making an invention known, through public disclosures or other acts, before filing a patent application. Otherwise, these disclosures threaten the patentability of an invention. The U.S. patent laws provide a one-year grace period for inventors to file a patent application after making a public disclosure implicating an invention2, but outside the United States (OUS), this grace period does not exist.3 Notwithstanding this difference, all patent systems share the aim of promoting public disclosure of technology through publication of inventions in exchange for the possibility of market exclusivity.   

  
Most medical device companies are mindful of the distinction between the U.S. patent system and OUS systems, and most companies are diligent in making sure that public disclosures are not made until patent applications have been filed in order to preserve OUS rights. However, under the right set of circumstances, the FDA's public disclosure procedures can pose a genuine threat to the patentability of a new device by revealing a critical feature. This paper will attempt to illuminate the circumstances in which events, mostly out of the control of the otherwise diligent and compliant device company, could conspire to deprive the company of valuable patent rights OUS.        

   
The interface of FDA regulation with domestic and foreign patent law and practice is jagged and complicated, and these functions are most often left to separate, independent, counsel that rarely interact substantively. Medical device companies often have regulatory counsel, U.S. patent counsel, and foreign patent counsel, the latter usually serving under the direction of U.S. patent counsel. In a large majority of the cases, the parallel and independent paths that regulatory and patent counsel follow are in harmony and create no problems. The vulnerability that this paper addresses is, however rare, quite possible, and the consequences are real. Fortunately, any risk can be mitigated by involving patent counsel in adverse event episodes reported to the FDA.       

    
This paper begins with a brief overview of the applicable law, and will then describe the interplay of events which could lead to the loss of OUS patent rights by a device company through a sequence of seemingly unrelated events.


II. What Type of Devices are Vulnerable?


The illustration of the issues discussed in this paper is well served through the use of a hypothetical. Assume that American manufacturer NQR, Inc., develops a new medical device it intends to market. As mentioned earlier, NQR must obtain FDA permission before the device can be placed on the market. NQR must, as a competitive reality, file patent applications directed to its new device before making public disclosures, including market release of the device, if NQR is to preserve its OUS patent rights. These two processes are addressed in turn.

B. Patent Matters


In order to encourage investment in research and development, the United States, as well as most other nations, offers something of a quid pro quo to prospective inventors. In exchange for full public disclosure of a new idea, an inventor (or assignee) is awarded a limited monopoly, or a patent, on the invention. The invention must be both novel and non-obvious, lest the invention be of no public benefit.         
The novelty requirement for U.S. patents is set forth in 35 U.S.C. § 102. Simply put, the patent applicant must have invented the subject matter before anyone else.39 If the subject matter was already known prior to the patent application, the invention is considered "anticipated" by pre-existing technology, known as the "prior art". An anticipation requires that the inventor's claim be disclosed by a reference which encompasses every element of the claim within its "four corners."40             
While the United States attempts to honor an inventor's presumed right to a patent, the inventor must file his patent application within one year of the discovery.41 This one-year grace period strikes a balance between the interests of the inventor and the promotion of science.42 Without such a provision, inventors might be encouraged to delay filing a patent application in order to extend the effective term of their patents.43      

  
Additionally, even if an invention is novel, patent laws require that an invention be non-obvious in light of the prior art:


A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.44


The prima facie case of obviousness consists of three elements.45 First, there must exist a motivation to modify or combine references:46
[T]he relevant inquiry is whether there is a reason, suggestion, or motivation in the prior art that would lead one of ordinary skill in the art to combine the references, and that would also suggest a reasonable likelihood of success.47
A patent can be obtained for an invention that is completely contained within the prior art as long as the combination of prior art is not readily apparent. The Federal Circuit has noted that "[t]he genius of invention is often a combination of known elements which in hindsight seems preordained."48


Second, there must be a reasonable expectation of success.49 "The consistent criterion for determination of obviousness is whether the prior art would have suggested to one of ordinary skill in the art that this process should be carried out and would have a reasonable likelihood of success, viewed in the light of the prior art."50 Finally, the prior art references must teach all the elements of the claim.51


In contrast to the American first-to-invent system, most countries OUS ascribe to a first-to-file patent scheme. These countries require absolute novelty of new patent claims. In other words, any prior public disclosure of the subject matter invalidates its patentability, regardless of the means of disclosure. Some narrow exceptions apply. The European Patent Office, for example, provides a six-month grace period if the invention was displayed at an international exhibition or if there was evident abuse in relation to the applicant.52 But in most instances, public disclosure by a company in any form (e.g., by publication, oral disclosure, presentation exhibit) before a patent filing will be available as prior art against any subsequently filed OUS patent application.


_________________________________________
Below we see what has been happening these few decades of CLINTON/BUSH/OBAMA only now it is going crazy----our Federal health agencies are now simply Wall Street captured acting as our SEC -----regulators are simply global corporate executives being rotated through our agencies----there is no public interest happening. This is why we have soaring medical harm much of which is never reported because our health institutions have no oversight and accountability and harm is hidden. The data coming from these for-profit health institutions is skewed and we only get bad reports when outside watchdog organizations do the oversight.
What Obama and Clinton neo-liberals like MIKULSKI, CARDIN, CUMMINGS, AND SARBANES did was to use Affordable Care Act policy to end all regulatory oversight calling is unaffordable. Now we have as in Baltimore BIOTECH PARKS tied to our universities that are geared to patent to market anything they think will sell. These are simply global corporations attaching themselves to our US universities and appointed executives have no connection to MORALS, ETHICS, RULE OF LAW----
'There are several striking things about Sarepta’s ($SRPT) FDA approval this week for its controversial and long-delayed DMD drug, but just how it gained approval from the U.S. regulator has become one of the most interesting, and perhaps just as controversial'.
'It was unlikely because much of the data used to back a speedy approval were based largely on a small study with no placebo control, comparing eteplirsen's results against historical data in the muscle-wasting disease'.
WE THE PEOPLE are being told these innovations must come to market for good of mankind---then after several years if millions of people die---they will reformulate until brand name profitability is gone. If a developed nation citizens get to angry they will take it off the market and continue to sell it in developing nations.
WHEN WE HAVE SEEN FDA-APPROVED THESE ARE THE KINDS OF STUDIES DONE OVERSEAS ------NOW THEY ARE BRINGING THIS KIND OF RESEARCH AND MANUFACTURING TO THE US-----


'It was unlikely because much of the data used to back a speedy approval were based largely on a small study with no placebo control, comparing eteplirsen's results against historical data in the muscle-wasting disease'.


HARRAH! THE ONLY THING IMPORTANT IS PATENT SHARES SOARED!



'On the big question--Do the clinical results of the single study provide “substantial evidence” of eteplirsen’s efficacy--7 of the panel members voted no, with three voting yes and three abstaining.

Five months down the line, however, it has been approved, and Sarepta’s shares soared into the afternoon, up by more than 90% after midday'.


No storm for Sarepta, but has the FDA created its own tempest?
by Ben Adams |
Sep 19, 2016 1:46pm

There are several striking things about Sarepta’s ($SRPT) FDA approval this week for its controversial and long-delayed DMD drug, but just how it gained approval from the U.S. regulator has become one of the most interesting, and perhaps just as controversial.
Let’s go back to the start of the year when a massive snowstorm stopped the FDA from sitting down to discuss the drug, extending its PDUFA date by three months.
Then in April, more bad news when the agency’s group of experts rejected the med.
A month later, things took another turn when the FDA said it would miss its own preset PDUFA date of 26 May in order to sort out “internal conversations” about the drug. Many started to believe a rejection was coming.
Then, just a few weeks later, the FDA went a knockin’ at Sarepta for fresh data on the key biomarker for efficacy, and some optimism grew again.
Things then took a strange turn earlier this month when Dr. Ron Farkas, a fierce critic of Sarepta’s DMD drug, left the FDA unexpectedly to take on a consulting role at CRO Parexel ($PRXL), with no word from any party until reports of the move surfaced in the press, and each were forced to concede that he had moved on. Reasons for his departure were not given.

Some believed this was a sign of dissent from within the agency and that Dr. Farkas’ leaving was a signal that an approval was coming. A week after his move went public, eteplirsen, now known as Exondys, gained what seemed at times one of the most unlikely of approvals.


It was unlikely because much of the data used to back a speedy approval were based largely on a small study with no placebo control, comparing eteplirsen's results against historical data in the muscle-wasting disease.


Back in April, the FDA panel of outside experts voted narrowly, 7 to 6, that Sarepta did not provide substantial evidence from “adequate and well-controlled” studies that the drug produced dystrophin at a level that was reasonably likely to produce a clinical benefit.
On the big question--Do the clinical results of the single study provide “substantial evidence” of eteplirsen’s efficacy--7 of the panel members voted no, with three voting yes and three abstaining.


Five months down the line, however, it has been approved, and Sarepta’s shares soared into the afternoon, up by more than 90% after midday.


One of the big pressures for the FDA has been the lobbying power from hundreds of patient advocates, patients and families that have turned out to give their raucous support for an approval during the panel review and vote.


And backers have continued to protest--with widespread support from prominent elected officials and newspapers--that this is their last and only near-term hope for a drug that they insist has made a dramatic difference for slowly dying boys with this terrible disease that until this week had no specific treatments.
We may never know how much this lobbying helped in the approval of the drug, but one thing that has now come to light is the internal lobbying undertaken by Dr. Janet Woodcock, the CDER director.



In redacted documents released along with the approval, it is clear that it was Dr. Woodcock who helped push the drug through to approval--despite internal protestations from Dr. Ellis Unger, a senior doc at the agency, to FDA Commissioner Dr. Robert Califf.
Dr. Unger, among others, had expressed concerns at the small study and its lack of clear efficacy, but Dr. Woodcock, who in the past has been seen by some as leaning toward approvals rather than rejections, said the FDA must be “Prepared to be flexible with respect to a devastating illness with no treatment options.”



Last week, Dr. Califf said he would “defer” to Dr. Woodcock in this case and allow the green light.
In a more astonishing moment, detailed in the CDER documents, Dr. Woodcock said that Sarepta in particular “needed to be capitalized” and noted that the biotech’s stock had risen and fallen on a series of updates over the year.


In the documents, it recorded: “Dr. Woodcock cautioned that, if Sarepta did not receive accelerated approval for eteplirsen, it would have insufficient funding to continue to study eteplirsen and the other similar drugs in its pipeline. She stated that, without an approval in cases such as eteplirsen, patients would abandon all hope of approval for these types of products and would "lapse into a position of" self-treatment.
This will likely lead to some serious questions over the FDA’s processes and whether this sets a precedent for other rare and ultrarare meds--and how much a company’s stock and concerns over future research should be considered. Many at the agency clearly felt the question was over the data, so where does this leave the broader questions in future decisions?
Sarepta will under the approval still need to show more data that its drug works, or face having it yanked off the market. Some will see this as a flexible approach in a disease with no treatments, but others may question why a drug should gain approval, and then earn potentially hundreds of millions of dollars, if it turns out it did never did meet the regulator’s efficacy requirements.

__________________________________________

CLINTON era started this attack on all Federal agencies including this FDA-----Department of AG ----created during the FDR New Deal as public interest protection of food and PHARMA. This was what built a strong clinical trial and review process in the US. The US has from the beginning had public protections-----here we see colonial era protections and right now----with CLINTON/BUSH/OBAMA----we don't even have those basic protections as global markets open to any developing nation product comes with no oversight and accountability and in regards to health care these global health industry corporations have been overseas operating with absolutely no Western standards of research.

THIS FDA/DEPARTMENT OF AG IS ONE OF THE LAST IN A LONG LIST OF NEW DEAL PUBLIC INTEREST POLICY THAT HAS BEEN DISMANTLED AND THROWN AWAY COURTESY OF BILL AND HILLARY CLINTON-----AND REPUBLICANS.


'Food production in the United States has been regulated since the late eighteenth century. Colonies and, later, states passed laws banning impurities from selected foods. In 1848, the United States began regulating imported drugs, under the Drug Importation Act (Ch. LXX, 9 Stat. 237). The enforcement of food and drug laws was first assigned to the Chemical Division of the new u.s. department of agriculture (USDA) in 1862 (12 Stat. 387)'.

All scientists know 1% Wall Street has so broken down these review processes every time rolling out reasons when we all know it is mostly about profits. Sure, there have been times and products that needed to be expedited-----today they are simply creating an entire health industry of INNOVATION that tells us it all needs to be expedited.



Food and Drug Administration

West's Encyclopedia of American Law
COPYRIGHT 2005 The Gale Group, Inc.

FOOD AND DRUG ADMINISTRATION

One of the oldest U.S. consumer protection agencies, the Food and Drug Administration (FDA) protects the public from unsafe foods, drugs, medical devices, cosmetics, and other potential hazards. As part of the department of health and human services, the FDA annually regulates over $1 trillion worth of products, which account for one-fourth of all consumer spending in the United States. It also protects the rights and safety of patients in clinical trials of new medical products, monitors the promotional activities of drug and device manufacturers, regulates the labeling of all packaged foods, and monitors the safety of the nation's blood supply.
To ensure compliance with its regulations, the FDA employs over 1,000 investigators and inspectors who visit over 15,000 food-processing, drug-manufacturing, and other facilities each year. If it finds violations of law, the FDA first encourages an offending company to voluntarily correct the problem or to recall a faulty product from the market. If the firm does not voluntarily comply with the law, the FDA may take it to court and seek criminal penalties against it. The FDA may also seize faulty products, order product recalls, seek injunctive relief, impose fines, and take other types of enforcement action. Each year, the FDA declares about 3,000 products and 30,000 import shipments to be unacceptable in various ways.
The FDA employs over 2,000 scientists—including 900 chemists and 300 microbiologists—who provide the scientific evidence to back up its regulatory and inspection duties. These scientists analyze samples of products for purity and review test results of new products. The FDA itself does not do research for a new medical product. Instead, it evaluates the results of studies undertaken by the manufacturer.


History

Food production in the United States has been regulated since the late eighteenth century. Colonies and, later, states passed laws banning impurities from selected foods. In 1848, the United States began regulating imported drugs, under the Drug Importation Act (Ch. LXX, 9 Stat. 237). The enforcement of food and drug laws was first assigned to the Chemical Division of the new u.s. department of agriculture (USDA) in 1862 (12 Stat. 387).
The need for laws to regulate food and drug purity became increasingly urgent in the late nineteenth century, when substances such as opium, cocaine, and heroin were commonly added to medicinal elixirs and tonics. The need for government regulation was also made evident in Upton Sinclair's book, The Jungle, which exposed the unsanitary conditions of Chicago's meatpacking industry and shocked the nation. On June 30, 1906, Congress, with the support of President theodore roosevelt, passed two landmark pieces of Progressive Era legislation that strengthened the government's ability to protect consumers: the Food and Drug Act (34 Stat. 768 [21 U.S.C.A. § 1–15]) and the Meat Inspection Act (21 U.S.C.A. § 601 et seq.). The former prohibited interstate commerce in misbranded and adulterated foods, drinks, and drugs, and the latter addressed the unsanitary conditions and use of poisonous preservatives and dyes in the meatpacking industry.
In 1927, Congress authorized the creation of the Food, Drug, and Insecticide Administration within the U.S. Department of Agriculture. In 1930, the agency's name was changed to the current one, Food and Drug Administration (Agriculture Appropriation Act, 46 Stat. 976).
In 1937, 107 people died after taking the elixir sulfanilamide, a supposedly healing tonic. This tragedy prompted the passage of the next major reform of food and drug law, the Federal Food, Drug, and Cosmetic Act of 1938 (21U.S.C.A. § 301 et seq.). The FDA was then entrusted with the regulation of cosmetics and therapeutic devices and was authorized to do factory inspections. Even more importantly, the act required new drugs to be tested on animals and humans for safety before being marketed. In 1957, the Food Additives Amendment (Pub. L. 85-250, Aug. 31, 1957, Stat. 567) required the evaluation of food additives to establish safety, and in the following year, the Delaney Clause (Pub. L. 85-929, Sept. 6, 1958, 72 Stat. 1784) forbade the use in food of substances found to cause cancer in laboratory animals.


How the FDA Approves New Drugs

The process by which the Food and Drug Administration (FDA) approves drugs as safe and effective is generally long and complicated, though it may vary according to the type of drug and the nature of the illness for which it is being developed. The FDA refers to drugs under development as investigational new drugs, or INDs.
The evaluation of new drugs requires the skills of many different FDA scientists and professionals performing a wide variety of tasks. Biochemists and molecular biologists evaluate the basic chemistry and biology of new chemical compounds and molecular structures. Toxicologists assess the potential harm of proposed drugs, and pharmacologists study how these drugs affect the body and are broken down and absorbed by it. Computer scientists create electronic models that aid in the understanding of new chemicals. Physicians evaluate the results of clinical trials, assessing both the beneficial and adverse effects of the drugs. And statisticians evaluate the design and results of controlled studies.


It is an expensive and time consuming process, particularly for the company developing the drug, called a drug sponsor. A sponsor spends an average of $359 million for each new drug brought to market. Typically, the process takes eight and a half years and may be divided into roughly three stages: preclinical trials, involving animal and other laboratory tests (lasting one and a half years on average); clinical trials, involving tests on humans (five years); and FDA review (two years).
Preclinical Trials Once a sponsor has developed a drug, it must test the drug on animals in the laboratory. In doing so, the drug sponsor must follow FDA guidelines and regulations. These tests, also called preclinical trials, are usually done on more than one species of animals. FDA guidelines call for the inspection of animal laboratories every two years to ensure that they are being operated according to the administration's regulations.
After short-term lab testing has been performed and the sponsor has deemed its results adequate, the sponsor submits test data and plans for future clinical trials to the FDA. FDA scientists, together with a local institutional review board composed of scientists, ethicists, and nonscientists, then conduct a thirty-day safety review to decide whether to allow testing on humans. The vast majority of new drugs tested in the laboratory are rejected by either the sponsor or the FDA because they are unsafe or ineffective.


If the FDA indicates approval, the drug sponsor may begin clinical testing on humans. Even if a drug is approved for clinical trials, the sponsor continues animal testing of the drug in order to better understand the drug's long-term effects.


Clinical Trials Clinical trials are scientifically controlled studies in which the drug being tested is given to one group of patients, while another treatment, often a placebo (an inactive substance that looks like the drug being tested), is given to another group. Ideally, neither group of patients knows which is receiving the new drug and which is receiving the placebo.


The clinical trials, like the animal tests, examine what happens to the drug in the body, including whether it is changed, or metabolized, in the body, how much of it is absorbed into the blood, and how long it remains in the body. If human tests produce unexpected results, researchers may conduct further animal tests to better understand the drug.



Clinical trials proceed in three phases:


Phase 1 involves testing primarily for safety and dosage level. Twenty to one hundred healthy patients are assessed over several months. If the results are within FDA safety guidelines, the trials proceed to phase 2.


Phase 2 involves a greater number of patients—up to several hundred—who have the condition that the drug is intended to treat. During this stage, which lasts from several months to two years, researchers attempt to determine the drug's effectiveness in achieving its stated purpose, as well as its safety. At the end of this phase, sponsors meet with FDA officials to discuss the best way to conduct the next phase of testing.


In phase 3, the most crucial stage of testing, the number of patients is expanded still further, to several hundred to several thousand, and the length of the study is increased to one to four years. This phase establishes the correct dosage of the drug and how it will be labeled, and provides further evidence regarding its safety and effectiveness.


Of one hundred drugs submitted for testing in humans, an average of seventy will pass phase 1. Of these seventy, on average, only thirty-three will remain after phase 2 testing, and twenty-five to thirty after phase 3. Finally, an average of only twenty will actually receive FDA approval.


Once the drug sponsor has completed clinical trials, it submits a new drug application (NDA) to the FDA, requesting approval to market the drug. This application consists of documentation detailing the chemical composition of the drug, the design of the trials, the results of the trials, and the means by which the drug is made and packaged.
FDA Review In assessing an NDA, the FDA undertakes its closest scrutiny of all during the drug approval process. Its principal goal during review is to determine whether the benefits of the new drug outweigh the risks. To reach this determination, the FDA examines the documentation provided by the sponsor and looks at samples of the drug.
If inadequacies are discovered in the NDA, the FDA may require additional information, further testing, or modified labeling. In cases where it is difficult to establish clearly whether the benefits of the drug outweigh the risks, a panel of outside experts is often consulted.


If the FDA approves the drug, the sponsor may begin manufacturing and marketing the drug immediately.
The FDA does not stop monitoring a drug once it has been marketed. It continues to evaluate the drug's safety and effectiveness through its program of postmarket surveillance. This program consists of surveys, the testing of product samples, and the analysis of reported adverse reactions.

Speeding Drugs to Those Who Need Them The FDA has longstanding policies allowing what it calls the compassionate use of new drugs for those in desperate need. Innovative cancer treatments, for example, have been made available to patients since the 1970s through the National Cancer Institute.


However, during the 1980s, the FDA came under increasing fire for its slow approval of new drugs. Particularly with the emergence of AIDS during the 1980s, the public outcry for fast delivery of innovative new drugs strengthened. As science produces ever more pharmaceuticals, the FDA is called on to review drug applications as quickly as is reasonably possible.
In response to the growing demand for speedy drug evaluation, the FDA has made significant changes in its review protocols. In 1987, for example, the agency adopted "expanded access" regulations, which permit certain drugs to be designated as treatment INDs. A treatment IND may be administered to patients even while it is still undergoing clinical trials. This program allows patients with no other alternatives to undergo a treatment that may benefit their health. By August 1994, twenty-nine agents had been designated treatment INDs, and by 1995, more than seventy-five thousand patients had received access to new therapies through this program. New drugs used to treat patients with AIDS are made available through a similar process known as the parallel track approach.


Identifying priorities is another method the FDA uses to provide more rapid access to promising new treatments. AIDS drugs, drugs that treat life-threatening or severely debilitating illnesses, and drugs that appear to offer significant improvements over existing therapies are classified as priority drugs and receive faster review than those classified as standard drugs. With priority drugs, the FDA typically becomes involved earlier in the development process, and is thereby able to more quickly review the relevant applications.
Drugs are also classified as to chemical type, so that those closely similar in structure to existing drugs will receive less intensive review than those with a molecular structure that has never been marketed before.


Accelerated approval is another mechanism for faster review of promising new drugs. Under this program, created in 1991, a product may be approved for limited use if it has been shown in trials to achieve particular results—such as lowering blood pressure or cholesterol. Drugs approved under this program include didanosine for AIDS, interferon beta-1B for multiple sclerosis, and DNase for cystic fibrosis.


The Prescription Drug User Fee Act of 1992 (Pub. L. 102-571, Title 1, Oct. 29, 1992, 106 Stat. 4491 to 4500) has also enabled the FDA to speed drug review. Under this law, fees paid by drug manufacturers are used by the agency to hire hundreds of additional review staff and buy improved equipment, including computers that make review more efficient.


The FDA is also attempting to streamline red tape and bureaucracy. In 1995, President bill clinton and Vice President albert gore, Jr., announced that twenty-one separate product license applications used by the FDA would be consolidated into one simplified form. This form would also be available in an electronic format, making it easier to distribute, prepare, and review.


Results indicate that these changes have led to faster approval of important new drugs. One signal success of FDA reform was the prompt approval of taxol, a treatment for advanced ovarian cancer that was approved in December 1992 after a record 5 months. By 1994, all new drugs were being approved by the FDA in a median time of 19 months, and priority drugs with important therapeutic uses were approved in an average of 10.4 months. In the late 1980s, by comparison, the FDA took an average of 27 months to approve new drugs.


In 1995, President Clinton established even more ambitious new goals for FDA approval. These goals, to be met by 1997, require the FDA to approve priority drugs within 6 months and standard drugs within 12 months.


In 1962, the Kefauver-Harris Drug Amendments (Pub. L. 87-781, Oct. 10, 1962, 76 Stat.780) were passed. These laws required drug manufacturers not only to show that their drugs were safe but also to prove that their drugs achieved the effects claimed. That same year, FDA regulations were shown to be effective after the drug thalidomide, for which the FDA had delayed approval, caused thousands of birth defects in western Europe.
In 1979, the FDA was made part of the Department of Health and Human Services (96 Stat. 668, 695). Other laws with major implications for the FDA's activities include the 1990 Nutrition Labeling and Education Act (Pub. L. 101-535, Nov. 8, 1990, 104 Stat. 2353), which requires all packaged foods to carry labels with nutrition information, and the Prescription Drug User Fee Act of 1992 (Pub. L. 102-571, Title 1, Oct. 29, 1992, 106 Stat. 4491 to 4500), which requires drug and biologics manufacturers to pay fees that support FDA assessment of their products.


Effective October 2002, the FDA implemented its National Organic Program (NOP) under the Organic Foods Production Act of 1990 (OFPA), 7 U.S.C. 6501 et. seq. The NOP sets the first national standards for the use of the label term organic on food items and products. Products that qualify as "100 percent organic" under NOP rules may use the "USDA Organic" seal on their principal display panel. The rules specifically prohibit the use of genetic engineering methods, ionizing radiation (irradiation), and sewage sludge for fertilization. In addition, all agricultural products that are labeled organic must originate from farms or handling operations that have been certified by a state or private agency accredited by the USDA.


Organization

The FDA carries out its activities through a number of subdivisions. The Center for Drug Evaluation and Research regulates the safety, effectiveness, and labeling of all prescription and over-the-counter drugs intended for human use. It also monitors drug advertising for accuracy, ensures the safety and rights of patients in drug studies, and distributes information on drug products to the medical community and the public.

The Center for Biologics Evaluation and Research regulates biological products, which include blood, vaccines, human tissues, and drugs derived from living organisms. It coordinates an AIDS program, which works to develop an AIDS vaccine and AIDS diagnostic tests. It also conducts research on the safety of blood and blood products and inspects manufacturing plants to ensure compliance with FDA standards.

The Center for Food Safety and Applied Nutrition develops regulations related to food, food additives and colorings, and cosmetics. The Center for Devices and Radiological Health seeks to ensure the safe use of potentially hazardous radiation such as that produced by X rays. It conducts research into the effects of exposure to radiation-producing medical devices and develops manufacturing standards for such devices.


The Center for Veterinary Medicine evaluates the safety of drugs and devices used on animals. The National Center for Toxicological Research assesses the biological effects of toxic chemical substances.