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All Reason.com articles with the "FDA" tag.



Published: Mon, 23 Apr 2018 00:00:00 -0400

Last Build Date: Mon, 23 Apr 2018 04:41:52 -0400

 



This Could Be the First Cannabis-Derived Drug to Win FDA Approval

Fri, 20 Apr 2018 09:50:00 -0400

Epidiolex, a cannabidiol drug used to treat rare, severe forms of epilepsy in children, has moved one step closer to approval by the Food and Drug Administration, which could happen as soon as June. If approved, Epidiolex will be the first cannabis-derived drug recognized as a medicine under federal law. The FDA's announcement comes days before an independent, expert panel will vote on its safety. Because of Epidiolex's success in treating diseases with no alternative treatments, the FDA gave it "priority review" status in December, meaning the agency will review the application for the drug within six months (compared to 10 months under standard review). After the advisory board makes a recommendation to the FDA, the agency has until June 27 to reach a decision. The FDA staff report to the advisory committee says Epidiolex reduced seizures in a "clinically meaningful and statistically significant" way for patients suffering from Lennox-Gastaut syndrome and Dravet syndrome. The results of those studies provide "substantial evidence" of the drug's efficacy, the report says. Both Dravet Syndrome and Lennox-Gastaut are difficult to treat, as patients experience several types of seizures and are often resistant to medication. Patients who participated in the studies had taken other medications without adequate relief. Over two weeks, total seizures among Lennox-Gastaut patients who took Epidolex fell, on average, by 38 percent in one study and 44 percent in the other, while placebo patients experienced a drop of 18.5 percent and 23.5 percent, respectively. About 40 percent of patients in the cannabidiol (CBD) treatment groups saw a 50 percent or greater reduction in "drop seizures"—violent seizures that cause the upper body or full body to go limp, resulting in falls or injuries. Injuries from falling and poorly controlled seizures are cited as risk factors in the premature deaths of Lennox-Gastaut patients. The author of one Lennox-Gastaut study, Elizabeth Thiele, director of pediatric epilepsy at Massachusetts General Hospital, called Epidolex "life changing" in an interview with The Washington Post. "One child who comes to mind had multiple seizures a day," Thiele said. "She had been on every medication possible. She is now talking about college options. She would have never had that conversation before." In a Dravet syndrome study, cannabidiol cut the median number of monthly convulsive seizures in half, from 12.4 to 5.9. The median number of seizures in the control group fell only slightly, from of 14.9 to 14.1 per month. People with Dravet syndrome require constant care because of their frequent seizures, and 15 to 20 percent of them do not reach adulthood, dying at an average age of 8. The FDA has not approved any treatments specifically for Dravet syndrome. Since Epidiolex, made by the British company GW Pharmaceuticals, is not available yet in the United States, many families with children who suffer from Dravet travel to states where they can legally obtain CBD oil. Although 29 states and the District of Columbia allow medical use of cannabis, the federal government still classifies it as a Schedule I drug, meaning it is not legal for any use. A synthetic version of THC, another compound found in marijuana, has been available by prescription since 1985. But Epidiolex would be the first FDA-approved medicine derived directly from cannabis. Currently 1,100 epilepsy patients obtain Epidiolex through the FDA's Investigational New Drug program, which lets patients try medications that have not yet received FDA approval. If the FDA approves Epidolex, it would increase medical access and offer families an alternative to CBD oil, which is legal only in some states. It would also spur further research on cannabis-based medicine. "The important thing for us is that patients like this deserve a pharmaceutical solution," GW Pharmaceuticals Chief Executive Justin Glover told the Post. "They should not be moving across the country. They deserve the right to have access."[...]



Scott Gottlieb Is Not a Free Market Firebrand

Mon, 16 Apr 2018 06:00:00 -0400

It's mid-December, and Scott Gottlieb is at the Harvard Club. The Manhattan Institute has invited a few dozen people for an intimate discussion about what's happening at the Food and Drug Administration (FDA). As they eat finger foods and sip cocktails, a relaxed Gottlieb meanders around the room sans entourage and snags the occasional pretzel stick from a platter. As a former think tanker himself—he was an American Enterprise Institute resident fellow for roughly a decade—these are his people. Everyone takes their seats. Gottlieb's old friend Peter Huber, an attorney and senior fellow at the host institute, is sitting right up front. Just a few years earlier, the two had partnered to argue the affirmative in a debate over whether "the FDA's caution is hazardous to our health." But now that Gottlieb is the head honcho at the agency, some libertarians who once considered him a fellow traveler are finding him a tough nut to crack. When the floor opens for questions, one is about his plan to require cigarette manufacturers to lower the nicotine in their products to a "minimally or non-addictive level." "You want to take the nicotine out of cigarettes," the audience member says, incredulous. "Do you also want to take the alcohol out of booze?" "The FDA does not regulate alcohol products," Gottlieb responds. "Well, thank God for that," the questioner says, before plopping into his seat. The exchange demonstrates just one of the ways in which Gottlieb is not the person many onlookers anticipated. When Trump nominated him to be FDA commissioner in March 2017, conservatives and libertarians applauded his record of advocating market-based health care reforms, while liberals bemoaned his financial ties to the pharmaceutical industry and predicted death and destruction. They were both wrong. Instead of a radical deregulator, he has turned out to be a cautious institutionalist, focused on ensuring that his agency lives up to its obligations without exceeding the limits of its authority. Yes, he is nudging the FDA toward streamlining its approval process and encouraging competition in the drug and device markets. But Gottlieb was never going to burn the FDA to the ground, and people who thought he would weren't paying attention to what he's been saying all along. Shill "Scott Gottlieb's fervor for deregulation could harm patients," warned a piece published on the health news site STAT shortly after his appointment. "Farewell to drug regulation? Trump nominates a 'bona-fide pharma shill' to head the FDA," complained a Los Angeles Times headline. Gottlieb really is a longtime critic of the agency. At the Manhattan Institute, he speaks with the same polish he's demonstrated in hearings before Congress, repeating some of his favorite mantras: The FDA needs to "think differently" when it comes to biologic therapies and medical apps; "speed vs. safety" is a false choice the FDA doesn't have to make. At times he seems to channel a seminal 2012 essay he penned for National Affairs, titled "Changing the FDA's Culture," in which he bemoaned the agency's "excessive desire for certainty" and its "mistrust of the doctors who eventually prescribe medicines and the companies that market them." Gottlieb has argued repeatedly for reforming the way the FDA handles many of its duties, in particular the approval pipeline for drugs and medical devices. His criticisms were rooted in experience: He worked for the agency twice during George W. Bush's presidency, first as a senior advisor to Commissioner Mark McClellan and then as the deputy commissioner for medical and scientific affairs under Commissioner Andrew C. von Eschenbach. And like nearly every FDA commissioner before him, he has practiced medicine, as an internist and faculty member at the New York University School of Medicine. He also has extensive experience working with the drug companies he's now tasked with regulating. The federal disclosure form he filed with the U.S. Office of Government Ethics after his nomination listed board positions at Tivorsan Pharmace[...]



Happy 20th Birthday to Viagra, the Accidental Boner Pill That Changed America

Tue, 27 Mar 2018 16:45:00 -0400

Twenty years ago today, the Food and Drug Administration (FDA) approved orally administered sildenafil citrate tablets for the treatment of erectile dysfunction in the U.S., under the brand name Viagra. The little blue pill, the most popular use of which was discovered by accident, helped change how prescription drugs are marketed, and shifted public perceptions of what drugs can and should do. It was also an instant hit. Within two months of going to market, "approximately one million prescriptions had been written in the U.S. alone," according to a 2005 paper in the International Journal of Clinical Practice. But Pfizer Inc., the company behind the drug, had bigger ambitions for Viagra, which was the first treatment of its kind for erectile dysfunction. The company wanted to hit $1 billion in sales during its first year of availability, but was on track for only $800 million by December of 1998. To close the gap, Pfizer hired one-time GOP presidential candidate and former Sen. Bob Dole (R-Kans.) to serve as pitchman for the drug. Dole, then 75, was perfect for the role. A social conservative from the midwest who'd served in World War II, Dole acknowledged in May of 1998 that he'd participated in Viagra's clinical trial to treat the "impotence" he experienced as a result of undergoing surgery for prostate cancer in the early 1990s. "It is a great drug. I'll be honest. I was in the protocol and participated in the program," Dole said during a live appearance on CNN's Larry King Live. "There are many men out there, millions of men out there, who suffer from impotence, and this may be the first step." Various stories provide different explanations for how Pfizer learned sildenafil citrate worked better in the male member than the heart. In 2008, NPR told this story: Pfizer was testing it as a cardiovascular drug for its ability to lower blood pressure, but it raised something else, earning it the nickname "the Pfizer Riser." So how did the researchers find out? Well, the apocryphal story goes, you can take this or leave it, the trial subjects who took the drug for its original purpose, they wouldn't give back the samples. Last year, Quartz unearthed this story: All seemed to be going well—except for one weird thing the men enrolled in the study did when nurses went to check on them. "They found a lot of the men were lying on their stomachs," John LaMattina, who was the head of research and development at Pfizer while this research was ongoing, said on a 2016 episode of the STAT Signal Podcast. "A very observant nurse reported this, saying the men were embarrassed [because] they were getting erections." It appeared that the blood vessels dilating were not in the heart, but rather the penis. When Viagra went generic last year, Bloomberg's Joe Nocera noted its cultural impact thusly: Viagra was the first drug to allow impotent men to maintain erections. That made it the first true "lifestyle" drug and showed the pharmaceutical industry that there was money to be made developing drugs that improved people's lives without curing disease or alleviating pain. If creating a lifestyle drug was the first innovation, selling one was the second. Traditionally, companies sold drugs by having salespeople persuade doctors to prescribe them. But that wouldn't work for Viagra; doctors were as reluctant to ask patients about their sex lives as anyone else. The only way doctors were going to prescribe Viagra in large quantities was if patients asked for it. Dole's ads became a "textbook case in condition branding," Colgate University's Meika Loe told NPR in 2008. That model—in which direct-to-consumer ads "educate" patients about the symptoms of a disease they often didn't know existed as part of promoting a branded treatment—is now the lifeblood of the drug industry. src="https://www.youtube.com/embed/Kjhc0-6eSiw" allowfullscreen="allowfullscreen" width="560" height="340" frameborder="0"> It's probably one of the biggest reasons why prescription drugs that both work and fee[...]



What If Trump Signs a Right-to-Try Law and Nothing Happens?

Tue, 27 Mar 2018 11:35:00 -0400

House Republicans passed a "right-to-try" bill late last week after failing to gather the necessary votes a week earlier. The legislation, which expands patients' ability to seek experimental treatments, now heads to the Senate, which passed its own, looser version of a right-to-try bill last summer. Politico has a rundown of the back and forth, including some oddly vague positioning by Sen. Chuck Schumer (D–N.Y.). I would bet that some version of a right-to-try bill makes its way to President Donald Trump's desk eventually, and that when it does he'll sign it. But the politics of the bill aren't as interesting to me as what happens once we do have a federal right-to-try law. In the best-case scenario, the law saves lives that would otherwise be lost. Doctors whose patients are terminally ill and incapable of benefitting from currently approved therapies or participating in a clinical trial would be able to request experimental drugs from pharmaceutical companies and then administer them, all without seeking approval from the Food and Drug Administration (FDA). In this scenario, pharmaceutical companies would be willing to sell (or donate) these investigational drugs, which, by law, would need to have passed only the first safety stage ("Phase I") of clinical trials. Ideally, some number of people would receive a treatment years before the FDA approves it, the treatment would work in a way that no other treatment has, and the patients would outlive their current prognosis. This scenario relies on some assumptions that we cannot currently test. The first assumption is that there is a large pool of people who would benefit from right-to-try who are not benefitting from the FDA's existing Expanded Access/Compassionate Use program. When patients have exhausted all approved treatment options and failed to gain admission to a clinical trial, doctors can apply for the FDA's permission to use an investigational drug. The approval rate for Expanded Access is 99 percent and the agency recently simplified the application process, but we don't know much about the one percent who are rejected, or how many doctors and patients feel overwhelmed by the application process, or whether the application process is structured in such a way as to discourage certain types of doctors and patients from ever applying. In 2017, 1,143 Expanded Access applicants were allowed to proceed, while only eight were not. I have seen no estimates of the number of people likely to seek access under right-to-try; it could be dozens or thousands or zero. The second assumption is that drug developers are willing to participate in this partially deregulated market. The legislation, after all, does not require manufacturers and developers to provide drugs to a doctor; it only gives them the legal option to do so, and some protection from civil liability. But it is far from clear that any established drug maker wants to test those waters. Every calculation that drug developers make is aimed at increasing the odds of obtaining FDA approval and the subsequent period of monopoly. When they cut corners, it is to maximize profits. When they exercise an abundance of caution, it is to maximize profits. When they mess around with patent laws and voluntarily impose restricted distribution and make side deals with generic companies, they do all of that to maximize profits (which makes even more sense when you consider that the U.S. is where most drug makers can turn the biggest profit). How does right-to-try maximize a drug developer's profits? Under the House version, adverse events that reflect a drug's safety profile must be reported to the FDA. That adverse event could extend the length of the developer's clinical trial. It could even cause the FDA to issue a hold. What drug developer wants to trust that risk with a third party whose primary interest is not maximizing the drug company's profits? While I think right-to-try would better position patients and their doctors to demand access t[...]



FDA’s Low-Nicotine Cigarette Scheme Is an Invitation to Black Market Vendors

Mon, 26 Mar 2018 00:00:00 -0400

Technically, the Food and Drug Administration's new proposal "to lower nicotine in cigarettes to minimally or non-addictive levels" isn't an exercise in prohibition. Cigarettes would still remain available—but they wouldn't be the product that smokers had in mind. Instead, they'd be a substitute foisted on them by their self-identified betters. This sort of not-quite prohibition isn't new, and it's guaranteed to have very familiar consequences. In a statement linked to the FDA's advanced notice of proposed rulemaking, Commissioner Scott Gottlieb asks "What unintended consequences—such as the potential for illicit trade or for addicted smokers to compensate for lower nicotine by smoking more—might occur as a result?" I'm glad he asked. Low-nicotine cigarettes sound an awful lot like the 3.2 percent beer that plagued much of the country after Prohibition. Nobody was happy with the diluted swill, and they tolerated it only if they couldn't smuggle in something better. Most places have since dumped it, indicating that a taste for the unadulterated product remained strong even after years of restrictions. "Colorado has already changed their liquor laws and will permit stronger beer to be sold in grocery stores beginning in 2019, leaving only three states (Utah, Kansas and Minnesota) with laws mandating these low alcohol 'baby beers' that even the majors have less interest in brewing for them," reports American Craft Beer. There's no particular reason to think that smokers will be happier with denatured tobacco than drinkers have been with weak beer. Gottlieb has said "the FDA has a science-based obligation that supersedes popular trends and relies on evidence." Such stiff-necked sincerity is swell, but it can't make people like having their choices constrained by professional scolds. We've seen clear consequences of efforts to constrain choices in states where marijuana is newly legalized. It turns out that when you try to replace illegal markets with overtaxed and highly regulated legal ones, you throw a lifeline to underground dealers. "Pot black market still thrives after Colorado legalization," PBS reported in 2014 after the state introduced a hobbled form of legalization. "An ounce of pot on the black market can cost as little as 180 dollars," according to correspondent Rick Karr. "At the store Andy Williams owns, you have to pay around 240 dollars for an ounce. That's partly because the price includes a 15 percent excise tax, a 10 percent marijuana tax, the state sales tax, and Denver's marijuana sales tax." California officials are seeing similar results in their overregulated and overtaxed new non-medical marijuana market. Three months into a very tepid legalization, sales from legal vendors remain slow as "high taxes, complicated regulations and a thriving black market are having deleterious effects," according to the Sacramento Bee. Federal policies making it dangerous for financial institutions to transact with newly legal (at the state level) marijuana dealers also work to keep black markets alive. "[S]tate marijuana commerce will stay as black a market as bootlegged rum during Prohibition until banks find ways to operate under restrictive financial laws stemming from the Controlled Substances Act," the Alaska Journal of Commerce noted. Tobacco isn't all that different a product than alcohol or marijuana, and the burdensome taxes and regulations under which the stuff is sold have already created healthy opportunities for smugglers and bootleggers. "Excessive tax rates on cigarettes approach de facto prohibition in some states, inducing black and gray market movement of tobacco products into high-tax states from low-tax states or foreign sources," says Scott Drenkard of the Tax Foundation which, with the Mackinac Center for Public Policy, tracks cigarette smuggling on an ongoing basis. Under existing rules, an estimated 56.8 percent of cigarettes consumed in New York come from illegal sources. Enforce[...]



Eating Insects Could Be the Future of Culinary Innovation

Sat, 17 Mar 2018 07:15:00 -0400

Here in the U.S., we tend not think of insects as food, and are horrified when they turn up in food. Though finding a bug in one's meal is often cause for alarm and disgust, the laws around U.S. food standards recognize that bugs making their way into what we eat is simply a fact of life. FDA regulations known as the "Food Defect Action Levels" allow certain enumerated amounts and types of insects to be present in many foods. Take frozen orange juice. FDA rules specify that frozen orange juice is acceptable for sale if it contains fewer than "5 or more [fruit fly] and other fly eggs per 250 ml or 1 or more maggots per 250 ml." Canned corn, meanwhile may be sold containing "larvae, cast skins, larval or cast skin fragments of corn ear worms or corn borer," so long as the aggregate length of bug parts does not exceed 12 millimeters in 24 pounds of product. (The rules also discuss the maximum number of rodent hairs various foods may contain.) But in other parts of the world, people eat insects on purpose. The United Nations calls insects "a highly significant food source for human populations." Another source claims people in 80 percent of all countries—one of every three humans—eat bugs. The things we want to keep out of our food are actually a great source of protein, fat, and fiber. Yet in a world full of willing bug eaters, it's perhaps no surprise that the law—the thing that so often dictates what we may or may not eat—prevents us from thinking of grubs as grub. A fascinating piece this week by Massimo Reverberi, founder of a Thailand-based bug-pasta company, suggests a regulatory divide between the English-speaking world, which he says has been welcoming of edible bugs, and the EU, which he reveals "have felt the need to have rules and provide approvals before allowing any marketing." Reverberi writes that the U.S. and its FDA—the same agency that establishes Food Defect Action Levels for bugs in common foods marketed in the United States—has been surprisingly good about establishing permissive regulations for edible-insect foods. Others recent news backs that up. "Last week, the Enterra Feed Corporation, based in British Columbia, was approved by the Association of American Feed Control Officials to sell insect-based [animal] feed in the United States," writes author James McWilliams in a piece this month for Pacific Standard. While rules in the United States aren't unkind to those who would market bugs, this country nevertheless has been slow to adopt the trend of eating creepy crawlers. In the early 1990s, while a college student in Washington, D.C., I drank many drinks and ate many bugs as the Insect Club, which, as the name suggests, was not only insect-themed in its décor but also in its bar snacks. I thought the bug trend might take off then. It didn't. But that's clearly changing. Safeco Field, home of the Seattle Mariners, began offering toasted chili-lime grasshoppers during games last year. I tried them during a spring game and found them to be a damn tasty beer snack. The grasshoppers proved so popular that Poquito's, the local Mexican restaurant that offers up the grasshoppers, was forced to cap sales. In addition to grasshoppers, crickets seem a particularly popular offering. "Crickets are the gateway bug," bug-flour entrepreneur Jarrod Goldin told Fortune in 2016. San Francisco-based Don Bugito started out as a bug-centric food truck specializing in pre-Hispanic foods of the Americas. It now sells a variety of insect-based foods, including chocolate-covered bugs and cricket-flour granola. A food truck in Belgium has also capitalized on the "roach coach" insult by selling skewered bugs, dubbed "crickets on a stick." "They aren't really crickets, they're grasshoppers, but it sounds better to say cricket on a stick," says owner Bart Smit. Bug sales look set to skyrocket. "[M]arket research predicts farmed insect production will rise 102 percent between now an[...]



'Right to Try' Bill Fails, Despite Concessions

Wed, 14 Mar 2018 11:30:00 -0400

House Republicans failed yesterday to garner the votes they needed to pass a heavily modified version of the Senate's "Right to Try" bill. The legislation would have brought the U.S. one step closer to allowing terminally ill patients more freedom to test unapproved pharmaceutical products. The House needed a two-thirds majority to pass the bill, as Republicans had suspended the rules in order to prohibit amendments being added on the House floor. The bill failed to reach that threshhold; the final tally was 259–140. Right-to-try laws create a legal mechanism for patients and their doctors to request experimental treatments without first being enrolled in a clinical trial or getting permission from the Food and Drug Administration (FDA). Thirty-eight states have passed such bills, but until federal law changes no pharmaceutical company has an incentive to operate outside the FDA's purview. Under the most recent House version of the bill, introduced by Energy and Commerce Committee Chairman Greg Walden (R-Ore.) and Health Subcommittee Chairman Michael C. Burgess (R-Texas), licensed physicians would be able to request a drug from the company that makes it so long as the drug had passed Phase I clinical trials. The bill does not require drug application sponsors or manufacturers to provide the drug. If they do opt to provide the treatment to a physician, the drug maker would be responsible for reporting the transaction to the FDA. Walden and Burgess announced on March 10 that they'd added several others layers of regulatory compliance atop the more loosely written Senate bill that passed last August. Specifically, Walden and Burgess say their version of the bill would: establish a robust informed consent to access unapproved drugs; specify that any unapproved drug being used must have an active FDA application and not be the subject of a clinical hold by the FDA; require the sponsor and manufacturer to notify the FDA after they make an unapproved drug available to an eligible patient; guard patients from purposefully misbranded or mislabeled drugs; provide liability protections for participating manufacturers, sponsors, physicians, clinical investigators, and hospitals unless there is reckless or willful misconduct, gross negligence, or an intentional tort; obligate sponsors and manufacturers to report adverse events in real time to the FDA; and provide certainty to manufacturers about how the FDA will use patient outcomes when evaluating new drug applications. These changes were intended to address several of the criticisms levied against right-to-try legislation by certain patient groups and medical ethicists, who have insisted throughout the debate that the FDA's "expanded access" program adequately serves terminally ill patients who have exhausted their options and want to try an experimental treatment. The NYU School of Medicine Working Group on Compassionate Use and Pre-Approval Access, for instance, has argued that because the FDA approves 99 percent of expanded access applications, there's no reason to cut the agency out of the process. The House bill sought to strike a compromise by requiring doctors and drug manufacturers to notify the FDA of adverse events in real time, and by allowing the FDA to take those events into consideration when reviewing drug applications. Nevertheless, Democratic leaders in the House led a charge against the bill. In February, dozens of patient groups asked Congress to vote down the bill, arguing that the recently passed Food and Drug Administration Reauthorization Act had already helped streamline the Institutional Review Board process and empowered the FDA to make clinical trials more inclusive. (Patients who wish to access an experimental treatment either under the FDA's current program or the House version of the Right to Try bill would first need to be rejected for a clinical trial.) Proponents of right to try, whic[...]



The First Amendment Applies to the FDA Too

Tue, 06 Mar 2018 08:00:00 -0500

If you use a beta-blocker called Corgard to prevent migraine headaches, you are taking advantage of an important if obscure element of modern medicine: physicians' ability to prescribe approved medicines for purposes not explicitly sanctioned by the Food and Drug Administration (FDA). Corgard is approved for angina and high blood pressure only, yet migraine sufferers and their physicians know that it has other useful properties as well. These so-called "off-label" uses of drugs are perfectly legal, yet regulators make it all but impossible for manufacturers to inform doctors about such uses. No law or regulation explicitly forbids it, but the FDA treats it as misbranding or fraud. The government has prosecuted numerous drug makers for off-label promotion, with penalties and settlements in the billions of dollars. But that could change soon. In the last few years, the agency has lost several cases in which federal courts have held that giving doctors truthful information about off-label uses is protected by the U.S. Constitution's First Amendment. And while prosecutors have continued to drag drug makers to court, new leadership at the FDA has finally signaled some willingness to obey the Constitution. In the waning days of President Barack Obama's administration, the agency issued a rule that reinforced its speech restrictions, but regulators are now reconsidering that position. Before a drug can be sold in the United States, it must be certified by the FDA as safe and effective for a specific "on-label" use—to treat high blood pressure or a certain kind of leukemia, for example. But once a drug has been approved, physicians may legally prescribe it for any other purpose. There is typically a long lag between clinical research findings and FDA approval of a new use; journal articles and presentations at scientific conferences far outpace the agency's process. So off-label prescribing makes it possible for patients to benefit from the most up-to-date medical knowledge. Off-label prescribing is ubiquitous in a number of medical specialties and, by some estimates, at least 20 percent of all prescriptions are written for off-label uses. A 2013 study, for example, found that about 30 percent of the prescriptions for oncology drugs were for off-label uses. Needless to say, off-label prescribing must be done judiciously. "Guesses" about possible uses of drugs may have deleterious results, as illustrated by a 2011 safety review of the heart drug Multaq. The approved, on-label use of the drug is to treat people with transient atrial fibrillation (an abnormal heart rhythm). However, according to the FDA, the drug increases the risk of serious cardiovascular events, including death, when used by patients with permanent atrial fibrillation. Prescribing Multaq for the latter condition because it is safe and effective for the former would put patients at grave risk. So doctors know they must continuously educate themselves about the risks and benefits of all the medicines they prescribe, for both on- and off-label uses. And drug manufacturers have a legal obligation to monitor the safety of their products long after they've been approved; whether they're promoting approved uses or off-label ones, the FDA has the authority to prosecute companies when they distribute false or misleading information. Similarly, drug companies can (and routinely are) sued by patients who believe some aspect of information is incorrect or misleading. Those are compelling reasons for manufacturers to continue to test their drugs long after approval, despite this rhetorical question posed by a former FDA official in the Washington Post, "If your drug is approved for X, why would you ever commit millions [of dollars] in additional testing to get approved for Y, when it's already legal to use it for Y?" If the threat of agency action or private litigation weren't enough,[...]



Balaji Srinivasan: Technology Will Lead to a Borderless World

Wed, 28 Feb 2018 12:14:00 -0500

"Soon you'll be able to join a VR world, and earn virtual currency in virtual reality," says Silicon Valley entrepreneur Balaji Srinivasan. "Which means that, for a good chunk of people in the world, the majority of their waking hours are going to be spent in the Matrix." Srinivasan believes that new technologies—mobile devices, cloud computing, cryptocurrencies—are rapidly taking us into an era when geography, nationality, and other limitations on our labor and freedom fade away. He says that this evolution will empower individuals and erode the authoritarian capabilities of the state. Srinivasan is a modern-day polymath who venture capitalist Marc Andreessen has called the person with "the highest output per minute of new ideas of anybody I've ever met in my life." A Ph.D. in electrical engineering, a co-founder of the genetic testing firm Counsyl, and a Stanford computer science lecturer, Srinivasan was also on Donald Trump's short list to head up the Food and Drug Administration. He believes in technology's power to provide a way for individuals to migrate away from ossified institutions and destructive policies. Borrowing a framework from a 1970 political science treatise by Albert O. Hirschman, Exit, Voice, and Loyalty: Responses to Decline in Firms, Organizations, and States, Srinivasan described his vision in a much-discussed 2013 talk titled "Sillicon Valley's Ultimate Exit." Today, he spends most of his time running the cryptocurrency-based startup Earn.com, which allows users to get paid for small tasks, like responding to emails and completing surveys. It is ultimately, he says, a tool for creating a "frictionless digital workforce." He imagines Earn.com providing users with a new type of decentralized employment based purely on their skills. Participants would log on, see a feed of tasks they needed to accomplish, and then be compensated accordingly. While teaching at Stanford a decade ago, Srinivasan and his brother Ramji founded the genetic testing firm Counsyl, which offers a single assay that tests for every major Mendelian genetic disease. The company aims to lower costs, empower parents, and improve the way genetic diseases are identified and treated. In a wide-ranging discussion, Reason's Nick Gillespie spoke with Srinivasan about his current ventures; how the FDA and other regulatory bodies should adapt to new technologies; the controversy over genetic testing and "designer babies;" how the 1997 book The Sovereign Individual has influenced his thought; his intellectual heroes; and how he's contributing to "Silicon Valley's ultimate exit." Interview edited by Justin Monticello. Camera by Paul Detrick and Monticello. Music by Grégoire Lourme, Silent Partner, Blue Giraffe, and Hare. Subscribe to our YouTube channel. Like us on Facebook. Follow us on Twitter. Subscribe to our podcast at iTunes. The interview has been edited for clarity. Check all quotes against the audio for accuracy. Balaji Srinivasan: One of the things I think a lot about is, if you've got an existing system, and it's ossified, there's at least two responses to it. There's more than two, but at least two. One is, you know, voice, which in its extreme is revolution. Revolution is extreme voice, where it's saying, "Oh, I'm so dissatisfied, let's take the whole thing over." And then democracy is, you know, like a much more limited version of that, but still also effective in many cases. You know, you could actually vote to go and change things. Alternatively, if you believe that it's going to be too hard to change things that way, but you're also cognizant of the fact that certain people like it that way, there's an alternative you can pursue, which is exit. You say, "Okay, I'm not going to be able to change the system, I recognize why you guys have it the way it is, but it doesn't suit my preferences, so I'm going to [...]



New York Times Columnist Is Worried About What's in His Urine

Mon, 26 Feb 2018 14:45:00 -0500

New York Times columnist Nicholas Kristof is very worried about what is in his urine, and he wants you to be too. In his latest piece, Kristof explains that he is very fastidious about avoiding contamination from endocrine-disrupting chemicals—that is, man-made substances that supposedly mimic the hormonal effects of estrogen and testosterone. Such substances, he tells us, are "blamed for an increase in undescended testicles and in a birth defect called hypospadias, in which the urethra exits the side or base of the penis rather than the tip." He is particularly anxious about avoiding bisphenol A (BPA), a chemical found in hard plastics, in the coatings of food and drink packages, and on the thermal paper used in some ATM and cash register receipts. Well, now he's had a new urine test, and he's eager to tell us the results. Living as he does a BPA-free lifestyle, he's happy to report that he had a low level of BPA. Alas, the test also found "high levels of a BPA substitute called BPF." In fact, Kristof reports that his Detox Me lab results from the Silent Spring Institute found that he tested "high" for four different endocrine-disrupting chemicals, including 1,4-dichlorobenzene, the effective ingredient in mothballs.* Exposure to that chemical is detected by measuring how much of its metabolite, DCP, is in your urine. A recent cohort study found that 81 percent of the U.S. population has DCP in its pee; in its biomonitoring summary, the Centers for Disease Control report that DCP averages about 5 parts per million in the urine of American adults. Kristof does not say whether his DCP level is higher than average. In any case, the Centers for Disease Control note that merely testing positive for DCP does not necessarily mean "an adverse health effect" is on the way. On the same day that Kristof published his column, the U.S. Food and Drug Adminstration (FDA) released the preliminary results from a long-term study being conducted at its National Center for Toxicological Research. Their research looks at the effects of several different doses of BPA, evaluating chronic and early-life exposure in two different groups of rodents. "The doses ranged from low doses that would be comparable to typical human exposures, to doses that vastly exceed human exposures," according to the FDA statement. "A variety of endpoints were evaluated including growth, weight and tumor development. Overall, the study found 'minimal effects' for the BPA-dosed groups of rodents." The agency added, "Our initial review supports our determination that currently authorized uses of BPA continue to be safe for consumers." It similarly reaffirmed its earlier evaluation of some 300 scientific studies, which concluded that BPA is safe for consumers. Meanwhile, even the chemophobes at the Endocrine Disruption Exchange acknowledge that BPF's potency is "in the same order of magnitude and of similar action as BPA." In addition, a new study** finds that BPF does not function as an endocrine disruptor. And what about Kristof's concern over hypospadias and undescended testicles? A 2010 review reported that "the bulk of evidence refutes claims for an increase in hypospadias rates." More recently, a population-based study in Nova Scotia found no increase in hypospadias or undescended testicles between 1988 and 2013. It's always fun to see some alarmism debunked the same day it's prominently promoted in The New York Times. *For what it's worth, I am highly allergic to mothballs. **Grain of salt: The study was supported by Valspar Packaging.[...]



Congress Has Failed (Yet Again) to Close the Martin Shkreli Loophole

Thu, 15 Feb 2018 15:20:00 -0500

Prescription drug companies sometimes use a legal loophole called "restricted distribution" to undermine their generic competitors. The CREATES Act, sponsored by a transpartisan group of senators, would have curtailed the practice, but last week Majority Leader Mitch McConnell (R-Ky.) excluded the bill from the budget agreement. As a result, Americans will continue to pay more than they should for certain prescription drugs. Many Americans are at least vaguely familiar with restricted distribution, thanks to the most infamous pharmaceutical executive to take advantage of it, Martin Shkreli. Shkreli, you may remember, jacked up the price of a drug called Daraprim, which was approved by the Food and Drug Administration in the 1950s and has been used for decades as a treatment for parasites that infect people with compromised immune systems. The patent for Daraprim expired more than 40 years ago, but it's still the only FDA-approved version of pyrimethamine currently on the market in the U.S., which means it has no generic competitor. (The FDA approved a slightly different formulation of pyrimethamine as a malaria treatment in 1981, but it has since been discontinued.) For a long time, American patients didn't really need a generic version of Daraprim, because it cost around $13.50 per 25 milligram pill and is taken for a short period of time. For immunocompromised adult patients who have the toxoplasmosis parasite, the FDA recommends taking 50 to 75 milligrams of Daraprim a day for up to three weeks, followed by half that dosage for an additional four to five weeks. So at the high end, an adult course of Daraprim therapy for a U.S. patient used to cost around $1,350 total. While that might not seem cheap, it was a drop in the bucket compared to the cost after Turing Pharmaceuticals, Shkreli's company, bought the rights to Daraprim and jacked the price up to $750 per pill in 2015. That move increased the cost of one course of treatment to around $75,000. At that point you might have expected another company to jump in and start offering a generic version of the drug. But Shkreli used a regulatory loophole to keep that from happening. You see, when a generic manufacturer wants to create a cheap version of a branded drug, it has to buy thousands of doses from the manufacturer in order to run comparison tests. Generic manufacturers use the results of these tests to prove to the FDA that their version is identical to the branded drug that the agency has already approved. More often than not, the company that holds the marketing and distribution rights to a branded drug will sell those comparison doses to the generic manufacturer without being obstructionist, because that's the trade-off for receiving a 20-year monopoly by way of a drug patent: The branded manufacturer gets to charge whatever they want for years and years without facing competition, and in exchange for that government-backed monopoly, it's supposed to sell equivalency samples to generic companies. But what if the company is run by an unscrupulous asshole like Martin Shkreli? Then it might opt to put the drug into what's called "restricted distribution," which means no distributor anywhere can sell comparison samples to a generic manufacturer. The FDA originally created the concept of restricted distribution to limit the availability of drugs that might be dangerous. Methadone, for instance, was first approved in the 1940s as a painkiller. In the 1970s, the FDA restricted its availability because regulators didn't want the opioid used for anything other than the treatment of opioid dependence. Even today, methadone can be dispensed only in highly regulated settings and only for one approved reason. In 2007, Congress empowered the FDA to create an entire system of safety controls beyond restrict[...]



The FDA Is Still Trying to Ban Kratom, a Potential Solution to the Opioid Epidemic

Mon, 12 Feb 2018 11:10:00 -0500

Last week, the Food and Drug Administration announced that the herbal supplement kratom possesses the properties of an opioid, thus escalating the government's effort to slow usage of this alternative pain reliever. Due to the substance's similar chemical structure to traditional opioids, FDA Commissioner Scott Gottlieb suggested using kratom to treat withdrawals poses a public safety risk: We have been especially concerned about the use of kratom to treat opioid withdrawal symptoms, as there is no reliable evidence to support the use of kratom as a treatment for opioid use disorder and significant safety issues exist. The FDA stands ready to evaluate evidence that could demonstrate a medicinal purpose for kratom. However, to date, we have received no such submissions and are not aware of any evidence that would meet the agency's standard for approval. While kratom is currently legal under federal law, this announcement follows the FDA's decision to block the importation of kratom products. In 2016, the Drug Enforcement Administration tried to place kratom in the same class of illegal substances as heroin, but a public outcry—and even some Congressional support for kratom—stopped that motion. Now that the FDA has conducted further medical analysis of kratom, the drug is more likely to be added to the "schedule" of restricted drugs. The FDA states that the number of deaths associated with kratom use has increased to a total of 44, up from a total of 36 since the FDA's November 2017 report. While the report suggests these cases "underscore the serious and sometimes deadly risks of using kratom," it is clear that the FDA is reaching. In the majority of deaths that FDA attributes to kratom, subjects ingested multiple substances with known risks, including alcohol. The presence of multiple drugs makes it difficult to determine the role any one of them played. The FDA cites one case where a 22-year-old man consumed a kratom mixture he ordered online along with an "unknown tablet." This consumption "was followed by an incident, during which the patient fell from a window of the first floor before going to bed" without receiving medical treatment. He was found dead the next morning, and the medical examiner determined that he choked on his vomit while he slept. The man had a history of mental illness, and a prescription drug history that included pipamperone (an antipsychotic used for treating schizophrenia), fluoxetine (an SSRI used to treat anxiety, OCD and depression), queiapine (another antipsychotic), olanzapine (another antipsychotic), etizolam (a benzodiazepine analog), pregabalin (a nerve pain medication often used to treat seizures), lorazepam (a benzodiazepine) and triazolam (a benzodiazepine used to treat severe insomnia that can also cause psychotic episodes). Oh, and he also used kratom. The FDA report does not discuss the extent to which these drugs may have contributed to the man's mental state, instead summarizing his demise with this line: "The patient was found dead in his bed on the morning following the consumption of an herbal mixture." Another kratom user in the FDA's report died from deep vein thrombosis—a type of blood clot the medical examiner says may have been related to the man suffering from obesity. While there is some research suggesting a correlation between DVT and intravenous opioid use in women, kratom is taken orally and the subject in this report was male. Deep vein thrombosis can also be hereditary, and the man had a long history of medical problems. As with all the incidents in the FDA's report, these two deaths are associated with kratom only because kratom was found in each man's system. While there is no question that kratom is a drug, the FDA is grasping for a reason to ban this subs[...]



FDA Begins Implementing Awful Food-Safety Law

Sat, 03 Feb 2018 08:00:00 -0500

America's farmers are on the alert this week as key provisions of the Food Safety Modernization Act (FSMA) begin to take effect. The law, which is being rolled out by the Food and Drug Administration (FDA) over several years, could have far-reaching implications for who grows—and doesn't grow—the food you buy. When Congress passed FSMA (pronounced FIZZ-muh) in late 2010—President Obama signed it into law during the first days of 2011—supporters touted the law as the most sweeping update of our nation's food-safety laws in more than 75 years. But both the law and its implementation are controversial. Many small farmers feared—and still fear—that the new regulations and high costs of complying with the law could squeeze them out of business. As evidence, they point to the giant farms and food producers who supported the law. While FSMA contains several provisions, one key facet of the law requires the FDA to "establish science-based minimum standards for the safe production and harvesting of fruits and vegetables." Bigger farms must comply sooner. Hence, as of this week, the produce rules apply only to America's largest farms. That means that this year, farms with more than $500,000 in sales will have to comply with FSMA. Next year, the rules will also cover farms with between $250,000 and $500,000 in sales. And in 2020, the rules will cover very small farms—those with revenue between $25,000 and $250,000. While this gradual implementation is likely better for small farmers than the alternative—being forced to comply right now—that hasn't allayed their fears. Many of those fears pertain to compliance costs. The relative compliance costs for small and large farms are stark. As I've noted previously, the FDA estimates FSMA will cost America's small farms about $13,000 each per year and its larger farms about $30,000 per year. That means that for some small farmers, compliance costs could eat more than half of their revenue. For larger farms, compliance costs will amount to less than one percent of revenue. As I detail in my book, Biting the Hands that Feed Us: How Fewer, Smarter Laws Would Make Our Food System More Sustainable, small farmers' concerns about that part of the law have been legion. This week, one Maine farmer shared his concerns about the law. Farmer Goran Johanson, while embracing some of what FSMA requires, says the law will place "a huge financial burden on us as farmers." He worries "there could potentially be a lot of infrastructure needs necessary" at his farm, including that he'll have to scrape together funds "to build a new produce packing house that will have washable surfaces on everything, which is an expensive investment." Just how much will FSMA benefit consumers? According to the FDA itself, not much. Even if FSMA is implemented perfectly, the law won't make our food supply much safer. That's according to the FDA's best-case estimates which, I wrote in 2014, would mean "a paltry reduction in cases of foodborne illness of between 3.7 percent and 5.4 percent." Again, that's the best-case scenario. A more likely outcome, I estimated, also using FDA data, is that foodborne illness cases might drop by around 2.6 percent. Why such little impact? As I detailed in 2015, FDA regulations are only capable of preventing, at most, "only one out of every five cases... of foodborne illness." That's because four of every five cases of foodborne illness can be traced to causes that have nothing to do with foods regulated by the FDA. Congress never should have passed a law with such high costs and such little return. Around the country, state agriculture departments and agricultural extension agents are working feverishly to help local farmers prepare to comply with the regu[...]



Right To Try Laws Are a Fine Start. Comprehensive Reform of the FDA's Drug Trials Would Be Better.

Fri, 02 Feb 2018 13:35:00 -0500

In his State of the Union address this week, President Trump urged Congress to pass right-to-try legislation that would allow patients suffering from terminal illnesses to access new drugs and other treatments that have undergone preliminary Food and Drug Administration (FDA) safety trials, but have not yet been shown to be efficacious in clinical trials. It's a good start. But it's no substitute for a top-down overhaul of the agency's entire process for testing and approving new drugs. Traditionally, patients only get access to new drug treatments once they are approved by FDA after passing through three phases of clinical trials. The goal of phase 1 trials is to test new compounds for patient tolerabilty and safety. Typically 20 to 100 patients participate in Phase 1 trials. Phase 2 trials aim to determine proper dosage levels for new treatments while also checking for further evidence that the new compound is safe and possibly efficacious. Several hundred patients may be enrolled in Phase 2 trials. Phase 3 trials focus on efficacy and monitor for adverse reactions and may involve thousands of participants. In Phase 3 trials, the efficacy of new medications is often benchmarked against current treatments. One recent report estimates that only 1 in 10 new drugs that enter clinical trials are eventually approved by the FDA. It is noteworthy that only 31 percent of drugs that currently enter Phase 2 studies go on to Phase 3 trials. In other words, more than two-thirds of biopharmaceuticals that pass through Phase 1 safety trials end up being deemed insufficiently efficacious as treatments for the diseases at which they are targeted. So far, 38 states have passed right-to-try legislation. Since drugs and medical treatments are regulated at the federal level, state laws so far have had little apparent effect on enabling patients gain access to experimental treatments. Consequently, right-to-try proponents want Congress to pass legislation that would allow patients with terminal illnesses to seek access to experimental drugs that have passed through Phase 1 safety trials. Many drugmakers have been reluctant to offer treatments not yet approved by the FDA on a right-to-try basis for fear being sued by patients or their heirs should bad outcomes occur. In addition, they worry that any adverse events among right-to-try patients would delay eventual FDA approval. Consequently, the proposed federal legislation provides that the makers of experimental drugs could not be held liable by patients for any untoward outcomes and that FDA regulators would be barred from taking into account the results of right-to-try treatments when reviewing such drugs for approval. Opponents of right-to-try legislation fear that it would enable unscrupulous practitioners to sell the moral equivalent of snake oil to desperate people. In addition, opponents point out that the FDA already has a compassionate use program that allows patients and their physicians expanded access to investigational drugs. New FDA administrator Scott Gottlieb recently announced changes that aim to speed up the process of providing access to drugs and devices for patients with serious conditions (generally prior to product approval), when there is no therapeutic alternative. In addition, the agency provided guidance to drugmakers clarifying that suspected adverse reactions from experimental treatments administered on a right-to-try basis must be reported "only if there is evidence to suggest a causal relationship between the drug and the adverse event." The FDA does also note that greenlighting access to experimental treatments does not require drugmakers to provide them to patients. Right-to-try is at best a band-aid. Comprehen[...]



Addicts Use Imodium to Help With Detox. That's a Terrible Reason for the FDA to Make It Harder to Get.

Wed, 31 Jan 2018 14:00:00 -0500

Over-the-counter medicine frees Americans to treat minor health issues without first consulting an expert. For no ailment is this freedom more of a godsend than a pesky case of the runs. You can grab a box of Imodium A-D (or the store brand of the active ingredient, loperamide), walk to the checkout counter, and pay, all without breathing a word about your messy butt to anyone. But now the opioid crisis has driven regulators into absurd fits of caution. The Food and Drug Administration (FDA) wants to make loperamide less accessible because opioid addicts might abuse it. And some in the health industry argue that you should have to ask a pharmacist and present a government-issued ID to buy the drug, as is currently the case with pseudoephedrine. In a statement published Tuesday, the FDA announced that it "continues to receive reports of serious heart problems and deaths with much higher than the recommended doses of loperamide, primarily among people who are intentionally misusing or abusing the product." In response to these reports, the agency wants loperamide manufacturers to limit the number of doses per package to a few days' worth and to make the pills available only in blister packs rather than bottles. Loperamide is a very, very mild opioid, and like all opioids, it slows down the muscles that send poop through your pipes. But unlike most other opioids, it's doesn't affect other parts of the body unless you take a shit-ton. The maximum therapeutic dose is 16 milligrams in the course of a day; people using it either to get high or to chase away withdrawal symptoms will take more than 100 mg. Doses that high can (but don't often) cause "adverse cardiac events." That's just a mild inconvenience, you might object, if the changes will protect people's hearts. But this week's FDA notice does not say how many people have died or been seriously injured from loperamide overdoses, how many adverse events might be avoided by changing to blister packs, or how much retooling loperamide production facilities will cost manufacturers (and ultimately consumers). These are not small asks. The answer to the first question tells us whether the second two are even worth considering; the second question helps us understand whether the imposition implied by the third is reasonable. Since the FDA isn't being forthcoming, how might we determine how many people are abusing loperamide? A good start would be to look at toxicology and mortality data. Here's the research I found on loperamide abuse published in the last two years: According to a 2016 study of loperamide-related deaths in North Carolina, published in the Journal of Analytical Toxicology, the North Carolina Office of the Chief Medical Examiner found above-therapeutic levels of loperamide in 21 deceased persons between 2012 and 2016; the drug is said to have played some role in 19 of those cases. In only one case—that of a 21-year-old male who had a history of overdoses—was loperamide the only drug present. A review of New York Poison Control data published by the Centers for Disease Control and Health and Human Services uncovers 22 cases of intentional loperamide abuse between 2008 and 2016; 15 of the patients had a history of opioid abuse. The average daily dose was 358 mg, and the full range was 34 mg (twice the daily recommended maximum) to 1,200 mg (75 times the maximum). The report does not disclose any fatal overdoses. The same study looked at the National Poison Database System and found 179 cases of intentional loperamide abuse from 2008 to 2016. The average loperamide dose across those cases was 196 mg, ranging from 2 mg to 1,200 mg. The paper includes clinical outcomes for 132 of those ca[...]