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75% Of The FDA’s Drug Review Budget Comes from the Biopharmaceutical Industry

A study done by Caroline Chen of ProPublica is showing a rather provocative finding that is challenging the objectivity of the FDA in its approval of new drugs.

Entitled: “FDA Repays Industry by Rushing Risky Drugs to Market”, Chen contends that the agency is beholden to the biopharmaceutical industry which pays three quarters of the FDA’s budget used for the drug review process.

So, how can a proper regulation be made against an entire industry that is paying for almost the entire process of regulation?

I think this is the real national security issue that has gone beyond the radar of the US representatives, assuming that they’re there to really serve and protect the people.

What is highly despicable about all of this is the fact that the FDA regulatory capture begun about 25 years ago, when the US was facing a “drug lag” because at that time, FDA’s new drugs approval rate was painstakingly slow.

Here’s the undeniable truth of why all of the FDA-approved drugs today with no proven health benefits whatsoever, and are still laced with highly toxic chemicals that are giving us significant side-effects that could lead to cancer in the long-term.

FDA Repays Industry by Rushing Risky Drugs to Market

Nuplazid, a drug for hallucinations and delusions associated with Parkinson’s disease, failed two clinical trials. In a third trial, under a revised standard for measuring its effect, it showed minimal benefit. Overall, more patients died or had serious side effects on Nuplazid than after receiving no treatment.

Patients on Uloric, a gout drug, suffered more heart attacks, strokes and heart failure in two out of three trials than did their counterparts on standard or no medication.

Nevertheless, the U.S. Food and Drug Administration approved both of these drugs — with a deadly aftermath. Uloric’s manufacturer reported last November that patients on the drug were 34 percent more likely to die from heart disease than people taking an alternative gout medication. And since the FDA fast-tracked approval of Nuplazid and it went on the market in 2016 at a price of $24,000 a year, there have been 6,800 reports of adverse events for patients on the drug, including 887 deaths as of this past March 31.

The FDA is increasingly green-lighting expensive drugs despite dangerous or little-known side effects and inconclusive evidence that they curb or cure disease. Once widely assailed for moving slowly, today the FDA reviews and approves drugs faster than any other regulatory agency in the world. Between 2011 and 2015, the FDA reviewed new drug applications more than 60 days faster on average than did the European Medicines Agency.

Europe has also rejected drugs for which the FDA accelerated approval, such as Folotyn, which treats a rare form of blood cancer. European authorities cited “insufficient” evidence of health gains from Folotyn, which shrinks some tumors but hasn’t been shown to extend lives. It costs more than $92,000 for a seven-week course of treatment, according to research firm SSR Health.

As patients (or their insurers) shell out tens or hundreds of thousands of dollars for unproven drugs, manufacturers reap a windfall. For them, expedited approval can mean not only sped-up sales but also — if the drug is intended to treat a rare disease or serve a neglected population — FDA incentives worth hundreds of millions of dollars.

“Instead of a regulator and a regulated industry, we now have a partnership,.. That relationship has tilted the agency away from a public health perspective to an industry friendly perspective.”

– Dr. Michael Carome, director of the health research group for the nonprofit advocacy organization Public Citizen, and a former U.S. Department of Health and Human Services official.

While the FDA over the past three decades has implemented at least four major routes to faster approvals — the current commissioner, Dr. Scott Gottlieb, is easing even more drugs’ path to market. The FDA okayed 46 “novel” drugs — whose chemical structure hadn’t been previously approved — in 2017, the most in at least 15 years. At the same time, it’s rejecting fewer medications. In 2017, the FDA’s Center for Drug Evaluation and Research denied 19.7 percent of all applications for new drugs, biologics, and efficacy supplements, down from a 2010 peak of 59.2 percent, according to agency data.

President Trump has encouraged Gottlieb to give patients faster access to drugs. “You’re bringing that down, right?” Trump asked the commissioner at a May 30 event, referring to the time it takes to bring drugs to market. “You have a lot of good things in the wings that, frankly, if you moved them up, a lot of people would have a great shot.”

Faster reviews mean that the FDA often approves drugs despite limited information. It channels more and more experimental treatments, including Nuplazid, into expedited reviews that require only one clinical trial to show a benefit to patients, instead of the traditional two.

The FDA also increasingly allows drugmakers to claim success in trials based on proxy measurements — such as shrunken tumors — instead of clinical outcomes like survival rates or cures, which take more time to evaluate. In return for accelerated approval, drug companies commit to researching how well their drugs work after going on the market. But these post-marketing studies can take 10 years or longer to complete, leaving patients and doctors with lingering questions about safety and benefit.

“Clearly, accelerated approval has greater uncertainty,” Dr. Janet Woodcock, head of the FDA’s Center for Drug Evaluation and Research, said in an interview. When only a single trial is used for approval, “in some cases, there may be more uncertainty about safety findings or with the magnitude of effectiveness.”

She attributed the increased use of expedited pathways to more drugmakers developing treatments for rare diseases, “where there’s unmet need, and where the patient population and providers are eager to accept more uncertainty.”

The FDA’s growing emphasis on speed has come at the urging of both patient advocacy groups and industry, which began in 1992 to contribute to the salaries of the agency’s drug reviewers in exchange for time limits on reviews. In 2017, pharma paid 75 percent — or $905 million — of the agency’s scientific review budgets for branded and generic drugs, compared to 27 percent in 1993.

“The virginity was lost in ’92,” said Dr. Jerry Avorn, a professor at Harvard Medical School. “Once you have that paying relationship, it creates a dynamic that’s not a healthy one.”

Industry also sways the FDA through a less direct financial route. Many of the physicians, caregivers, and other witnesses before FDA advisory panels that evaluate drugs receive consulting fees, expense payments, or other remuneration from pharma companies.

“You know who never shows up at the [advisory committee]? The people who died in the trial,” lamented one former FDA staffer, who asked not to be named because he still works in the field. “Nobody is talking for them.”

The drug industry’s lobbying group, Pharmaceutical Research and Manufacturers of America, continues to push for ever-faster approvals. In a policy memo on its website, PhRMA warns of “needless delays in drug review and approval that lead to longer development times, missed opportunities, higher drug development costs and delays in treatments reaching patients.”

The agency has internalized decades of criticism that painted it as an obstacle to innovation, said Daniel Carpenter, a professor of government at Harvard and author of a 2010 book on pharmaceutical regulation at the FDA. “They now have a built-in fear of over-regulation that’s set in over the last 20 years.”

To be sure, nobody wants the FDA to drag out drug reviews unnecessarily, and even critics acknowledge that there’s no easy way for the agency to strike the perfect balance between sufficient speed and ample information, particularly when patients have no other treatments available, or are terminally ill.

FDA Is Approving More New Drugs and Rejecting Fewer Overall

Sources: Center for Drug Evaluation and Research; Credit: Riley Wong

“I think it’s reasonable to move drugs faster particularly in the case where you’re dealing with an extremely promising new product which treats a serious or life-threatening disease,” said Dr. Aaron Kesselheim, an associate professor at Harvard Medical School. “The key, though, when you do that is that you’ve got to make sure you closely follow the drug in a thoughtful way and unfortunately, too often we don’t do that in the U.S.”

Gregg Gonsalves used to be a member of ACT UP, the HIV advocacy group that tried to take over the FDA’s headquarters in Rockville, Maryland, in 1988, accusing the agency of holding back cures. While he didn’t storm the FDA building, Gonsalves participated in other protests that led the FDA to accelerate approvals. Now an assistant professor of epidemiology at Yale School of Public Health, he said he fears HIV activists “opened a Pandora’s box” that the industry and anti-regulation think tanks pounced on.

“We were desperate. We naively had the idea that there were hundreds of drugs behind a velvet curtain at the FDA being held back from us,” he said. “Thirty years of our rash thinking has led us to a place where we know less and less about the drugs that we pay more and more for.”


After thalidomide, taken by pregnant women to prevent nausea, caused thousands of babies in the early 1960s to be born with stunted limbs, Congress entrusted the FDA with ensuring that drugs going on the market were both safe and effective, based on “substantial evidence” from multiple trials.

Assembling this evidence has traditionally required three stages of clinical trials; the first in a small cohort of healthy volunteers to determine a safe dosage; the second to assess the drug’s efficacy and side effects; and then, if results are positive, two larger trials to confirm the benefit and monitor for safety issues. An FDA team of in-house reviewers is then assigned to analyze the results and decide whether the agency should approve the drug. If reviewers want more input, the agency can convene an advisory committee of outside experts.

As the FDA’s responsibilities expanded in the 1970s, review times began to lag, reaching more than 35 months on average in 1979. The AIDS crisis followed soon thereafter, prompting complaints from Gonsalves and other activists. Their protests spurred the Prescription Drug User Fee Act in 1992, which established industry fees to fund FDA staff salaries. In return, the FDA promised to review drugs within 12 months for normal applications, and 6 months for priority cases.

The more that the FDA relied on industry fees to pay for drug reviews, the more it showed an inclination towards approval, former employees say.

“You don’t survive as a senior official at the FDA unless you’re pro-industry,” said Dr. Thomas Marciniak. A former FDA medical team leader, and a longtime outspoken critic of how drug companies handle clinical trials, Marciniak retired in 2014. “The FDA has to pay attention to what Congress tells them to do, and the industry will lobby to get somebody else in there if they don’t like you.”

Staffers know “you don’t get promoted unless you’re pro-industry,” he added.

This tilt is reflected in what senior officials choose to highlight. The agency’s Center for Drug Evaluation and Research gives internal awards to review teams each year, according to Marciniak and the former FDA employee who requested anonymity. Both said they had never seen an award granted to a team that rejected a drug application. The FDA did not respond to ProPublica’s request for a list of award winners.

Higher-ups would also send congratulatory emails to medical review teams when a drug was approved. “Nobody gets congratulated for turning a drug down, but you get seriously questioned,” said the former staffer, adding that the agency’s attitude is, “Keep Congress off your back and make your life easier.”

Dr. Peter Lurie, a former associate commissioner who left the FDA in 2017, recalled that John Jenkins, director of the agency’s Office of New Drugs from 2002 to 2017, gave an annual speech to employees, summing up the year’s accomplishments. Jenkins would talk “about how many approvals were done and how fast they were, but there was nothing in there saying, we kept five bad drugs off the market,” said Lurie, now president of the nonprofit Center for Science in the Public Interest in Washington, D.C. Jenkins declined to comment.

“I personally have no interest in pressuring people to approve things that shouldn’t be approved — the actual person who would be accountable would be me,” Woodcock said. She added that the FDA’s “accountability to the public far outweighs pressure we might feel otherwise.”


Congress has authorized one initiative after another to expedite drug approvals. In 1988, it created “fast track” regulations. In 1992, the user fee law formalized “accelerated approval” and “priority review.” When the law was reauthorized in 1997, the goal for review times was lowered from a year to 10 months. In 2012, Congress added the designation, “breakthrough therapy,” enabling the FDA to waive normal procedures for drugs that showed substantial improvement over available treatments.

“Those multiple pathways were initially designed to be the exception to the rule, and now the exceptions are swallowing the rule,” Kesselheim said.

Sixty-eight percent of novel drugs approved by the FDA between 2014 and 2016 qualified for one or more of these accelerated pathways, Kesselheim and his colleagues have found. Once described by Rachel Sherman, now FDA principal deputy commissioner, as a program for “knock your socks off, home run” treatments, the “breakthrough therapy” label was doled out to 28 percent of drugs approved from 2014 to 2016.

Nuplazid was one of them. It was created in 2001 by a chemist at Acadia Pharmaceuticals, a small biotech firm in San Diego. Eight years later, in the first of two Phase 3 trials, it failed to prove its benefit over a placebo.

The company, which had no approved drugs and hence no revenue stream, halted the second trial, but wasn’t ready to give up. Acadia executives told investors that the trials failed because the placebo patients had a larger-than-expected improvement. They asked the FDA for permission to revise the scale used to measure benefit, arguing that the original scale, which was traditionally used for schizophrenia assessments, wasn’t appropriate for patients with Parkinson’s-related psychosis. The agency agreed to this new scale, which had never been used in a study for drug approval.

Since there were no treatments approved for Parkinson’s-related psychosis, the FDA also granted Acadia’s request for the breakthrough therapy designation, and agreed that Nuplazid needed only one positive Phase 3 trial, instead of two, for approval.

In 2012, Acadia finally got the positive trial results it had hoped for. In a study of 199 patients, Nuplazid showed a small but statistically significant advantage over a placebo.

FDA medical reviewer Dr. Paul Andreason was skeptical. Analyzing all of Nuplazid’s trial results, he found that you would need to treat 91 patients for seven to receive the full benefit. Five of the 91 would suffer “serious adverse events,” including one death. He recommended against approval, citing “an unacceptably increased, drug-related, safety risk of mortality and serious morbidity.”

The FDA convened an advisory committee to help it decide. Fifteen members of the public testified at its hearing. Three were physicians who were paid consultants for Acadia. Four worked with Parkinson’s advocacy organizations funded by Acadia. The company paid for the travel of three other witnesses who were relatives of Parkinson’s patients, and made videos shown to the committee of two other caregivers. Two speakers, the daughter and grand-daughter of a woman who suffered from Parkinson’s, said they had no financial relationship with Acadia. However, the granddaughter is now a paid “brand ambassador” for Nuplazid. All begged the FDA to approve Nuplazid.

“Acadia or its consultants interacted with some of the potential speakers to facilitate logistics and reimburse for travel, as is common practice,” Acadia spokeswoman Elena Ridloff said in an email. “…All speakers presented their own experience in their own words.”

The only speaker who urged the FDA to reject the drug was a scientist at the National Center for Health Research who has never had any financial relationship with Acadia.

The witnesses’ pleas affected the panel members, who voted 12-2 to recommend accelerated approval. “If there were a safe and effective alternative on the market, I would not have voted yes,” said Almut Winterstein, a professor of pharmaceutical outcomes and policy at the University of Florida. “But I think that, in particular, the public hearing today was very compelling. There clearly is a need.”

Dr. Mitchell Mathis, director of the FDA’s division of psychiatry products, sided with the advisory panel, overruling Andreason. “Even this small mean improvement in a disabling condition without an approved treatment is meaningful,” Mathis wrote, adding that its safety profile was no worse than other antipsychotics on the market. Like other antipsychotics, Nuplazid carries a warning on the label of increased deaths in elderly patients with dementia-related psychosis. Since Nuplazid’s approval in 2016, Acadia has raised its price twice, and it now costs more than $33,000 a year.


As Nuplazid began to reach patients, reports of adverse events poured in. While it’s impossible to ascertain whether the treatment was responsible for them, the sheer numbers, including the 887 deaths, are “mind boggling,” said Diana Zuckerman, president of the National Center for Health Research.

In more than 400 instances, Nuplazid was associated with worsening hallucinations — one of the very symptoms it was supposed to treat.

That’s what happened to Terrence Miller, a former Hewlett Packard and Sun Microsystems employee who was diagnosed with Parkinson’s in the early 1990s. About five years ago, Miller began to experience mild hallucinations, such as seeing cats and dogs in his home in Menlo Park, California. At the time, he realized that the animals weren’t real, and the visions didn’t bother him, so he didn’t take any medication for them. But two years later, after surgery for a hip injury, the hallucinations worsened.

“He was convinced that he hadn’t had the surgery yet and people were going to harvest his organs,” recalled his wife, Denise Sullivan. “He’d see spaceships outside the window and they had to call security to help restrain him.”

In 2016, Dr. Salima Brillman prescribed Nuplazid. Miller tried Nuplazid twice, for a few months each time. His hallucinations became darker. “I’d say, ‘Who are you talking to?’ and he said, ‘They’re telling me to do bad stuff,’” Sullivan said. Afraid “he might hurt me because of what his evil ‘friends’ were telling him,” Sullivan, who was paying more than $1,000 a month for the drug out of her own pocket, then stopped the treatment.

What Sullivan and Miller didn’t know is that Brillman earned $14,497 in consulting fees from Acadia in 2016, ranking as the company’s seventh highest paid doctor, government records show. The top five prescribers of Nuplazid in Medicare, the government’s health program for the elderly, all received payments from Acadia. Dr. David Kreitzman of Commack, New York, prescribed the most: $123,294 worth of Nuplazid for 18 patients in 2016, according to data company CareSet. He was paid $14,203 in consulting fees.

Brillman and Kreitzman didn’t respond to multiple requests for comment.

Miller’s new doctor switched him onto Seroquel, an old drug long used off-label for Parkinson’s-related psychosis. With it, he’s sleeping better and the hallucinations, while remaining, have become more benign again, Sullivan said. Patients like Miller, whose hallucinations worsen, may not have been on Nuplazid for long enough, said Ridloff, the Acadia spokeswoman.

The 887 reported deaths of Nuplazid patients may be an undercount. A nurse in Kansas, who specializes in dementia care, said a resident in one of the facilities she worked at had no history of cardiac issues, yet died from congestive heart failure within a month of starting on Nuplazid. The nurse requested anonymity because she continues to work in nursing care facilities.

“We questioned the ordering physician whether this should be reported to the FDA in relation to Nuplazid and he said, ‘Oh no, the drug rep said this couldn’t have happened because of Nuplazid,’ and it was never reported,” she said.

Acadia’s Ridloff said such behavior by a sales representative would be “absolutely not consistent with our protocols, policies and procedures.”

She said that deaths are to be expected among patients who are elderly and in an advanced stage of Parkinson’s, and that Nuplazid does not increase the risk of mortality.

“Acadia’s top priority has been, and continues to be, patient safety,” she said. “We carefully monitor and analyze safety reports from clinical studies and post-marketing reporting to ensure the ongoing safety of Nuplazid. Based on the totality of available information, Acadia is confident in Nuplazid’s efficacy and safety profile.”

After a CNN report in April about adverse events related to Nuplazid prompted lawmakers to question the FDA, Gottlieb said he would “take another look at the drug.” Agency spokeswoman Sandy Walsh confirmed that that an evaluation is ongoing, and the FDA “may issue additional communications as appropriate.”


Nuplazid isn’t the only drug approved by an FDA senior official against the advice of lower-level staffers. In 2016, internal reviewers and an advisory committee called for rejecting a drug for a rare muscular disease called Duchenne muscular dystrophy. Only 12 patients participated in the single trial that compared the drug, Exondys 51, with a placebo. Trial results showed that Exondys 51 produced a small amount of dystrophin, a protein Duchenne patients lack. But the company didn’t show that the protein increase translated into clinical benefits, like helping patients walk.

Woodcock approved the drug. Internal FDA documents later revealed that she was concerned about the solvency of the drugmaker, Sarepta Therapeutics in Cambridge, Massachusetts. A memo by the FDA’s acting chief scientist recounted Woodcock saying that Sarepta “needed to be capitalized” and might go under if Exondys 51 were rejected. Exondys 51 went on the market with a price tag of $300,000 a year.

“We don’t look at a company and say they’ll have a lower standard because they’re poor, but we’re trying to recognize that, small or large, companies will never work on developing a drug if they won’t make a profit,” said Woodcock. “Our job is to work with the field, and with the firms to try and find a path forward,” especially on rare diseases where a large trial is impractical, she said.

Last month, the European Medicines Agency’s advisory committee recommended rejection of Exondys 51’s application, saying “further data were needed to show … lasting benefits relevant to the patient.”

Sarepta is asking the committee to reconsider, the company said in a June press release.

The debate over Exondys 51 centered on the value of a so-called surrogate endpoint, a biological or chemical measure that serves as a proxy for whether the drug actually treats or cures the disease. Surrogate measures speed drug development because they’re easier and quicker to measure than patient outcomes.

Some surrogate measures are well-established. Lowering cholesterol has been proven repeatedly to help reduce heart attacks and strokes. But others aren’t, like how much dystrophin needs to be produced to help Duchenne patients, raising concerns that drugs may be approved despite uncertain benefits.

The jury is still out on two other drugs, Folotyn and Sirturo, which received expedited approval based on surrogate measurements. There’s no proof that Folotyn helps patients with a rare cancer — peripheral T-cell lymphoma — live longer, while Sirturo, an antibiotic for multi-drug-resistant tuberculosis, has potentially fatal side-effects. Yet since both drugs were aimed at small or under-served populations, the FDA rewarded their manufacturers with valuable perquisites.

In a clinical trial, Folotyn reduced tumors in 29 of 107 patients, but the shrinkage lasted longer than 14 weeks in only 13 people. Since everyone in the study got Folotyn, it wasn’t apparent whether the drug would help patients do better than a placebo or another drug. Meanwhile, 44 percent of participants in the trial suffered serious side effects, including sores in mucous membranes, including in the mouth, lips and digestive tract, and low levels of blood cells that help with clotting. One patient died after being hospitalized with sores and low white blood-cell counts.

While tumor shrinkage is a commonly used surrogate measurement in cancer trials, it often has a low correlation with longer life expectancy, according to a 2015 study. “I would say to a patient, this drug may be more likely to shrink a tumor either partially or even completely, but that may in fact be a pyrrhic victory if it doesn’t help you live better or longer,” said Mikkael Sekeres, director of the leukemia program at the Cleveland Clinic Cancer Center, who voted against approving Folotyn at the FDA’s advisory panel discussion in 2009. He was out-voted 10 to four. Three years later, the European Medicines Agency rejected the drug.

Because peripheral T-cell lymphoma only affects about 9,000 Americans each year, the FDA designated Folotyn as an “orphan” drug, giving its manufacturer, Allos Therapeutics, tax incentives and at least two extra years of marketing exclusivity. Nevada-based Spectrum Pharmaceuticals acquired Allos in 2012. At more than $92,000 per course of treatment, Folotyn is Spectrum’s top-selling product, earning $43 million in 2017.

Dr. Eric Jacobsen, clinical director of the adult lymphoma program at Dana-Farber Cancer Institute in Boston, has become disillusioned with Folotyn since he helped Allos run the original trial. “Enthusiasm for the drug has waned,” he said. “It’s been on the market for a long time, and there’s no additional data suggesting benefit.” He now prescribes other options first, particularly because of the mouth sores Folotyn can cause, which make it painful to eat or drink.

The FDA approved Sirturo in 2012 without requiring Johnson & Johnson, the manufacturer, to demonstrate that patients on the drug were cured of tuberculosis. Instead, Johnson & Johnson only had to show that the treatment, when added to a traditional drug regimen, killed bacteria in the sputum faster than did the regimen alone. Sirturo was successful by that measure, but 10 patients who took it died, five times as many as the two in the group on placebo.

Dean Follmann, a biostatistics expert at the National Institutes of Health, voted as an FDA advisory committee member to approve Sirturo but wrestled with how to read the sputum data in light of the higher death rate: “The drug could be so toxic that it kills bacteria faster, but it also kills people faster.”

The imbalance in deaths during the trial “was a safety signal” that led the FDA to require “its most serious warning in product labeling,” known as a boxed warning, said agency spokeswoman Walsh. The packaging, she added, specified that Sirturo “should only be used for patients for whom an effective TB regimen cannot otherwise be provided. Thus, current labeling provides for a safe and effective use.”

Under a 2007 provision in the user-fee law, aimed at spurring treatments for developing nations, Sirturo’s approval qualified Johnson & Johnson for a voucher given to manufacturers who successfully get a tropical disease drug to market. The voucher can be used in the future, for any drug, to claim priority review – within six months instead of the usual 10. Time is money in the drug industry, and beating your competitor to market can be worth hundreds of millions of dollars. Vouchers may also be sold to other drugmakers, and have garnered up to $350 million. Sarepta received a voucher under a similar program for pediatric rare diseases when the FDA approved Exondys 51.

In South Africa, where Sirturo is mainly used, the drug is seen as a helpful option for highly drug-resistant patients. A study at one South African hospital by Dr. Keertan Dheda found that 45 out of 68 patients who took Sirturo were cured, as against 27 out of 204 before the drug was available. That doesn’t rule out the possibility that Sirturo may be killing a small subset of patients, said Dheda, but the risk is “very minor compared to the disease itself.”

Adrian Thomas, Johnson & Johnson’s vice president of global public health, said in an interview that observational results since the drug went on the market make him “much more confident that there is no more unexplained imbalance in mortality” and that the “benefit/risk in drug-resistant tuberculosis is incredibly reasonable when you don’t have other treatment choices.”

Still, the World Health Organization said in a 2016 report that the “quality of evidence remains very low” regarding Sirturo. “There is still some residual uncertainty for mortality,” the group said, and “specific harms” to the respiratory system “continue to be observed.”


While the FDA expedites drug approvals, it’s content to wait a decade or more for the post-marketing studies that manufacturers agree to do. Definitive answers about Sirturo are likely to be lacking until 2022, when Johnson & Johnson is expected to finish its study, a full decade after the drug was approved. Studies of Nuplazid and Folotyn aren’t expected until 2021. Spectrum has missed two FDA deadlines for post-marketing studies on Folotyn. Spectrum spokeswoman Ashley Winters declined comment.

Post-marketing studies often take far longer to complete than pre-approval trials, in part because it’s harder to recruit patients to risk being given a placebo when the drug is readily available on the market. Plus, since the drug is already on the market, the manufacturer no longer has a financial incentive to study its impact— and stands to lose money if the results are negative. Of post-marketing studies agreed to by manufacturers in 2009 and 2010, 20 percent had not started five years later, and another 25 percent were still ongoing.

And, despite taking so long, most post-marketing studies of drugs approved on the basis of surrogate measures rely on proxy criteria again rather than examining clinical effects on patients’ health or lifespans. In fact, Folotyn’s post-marketing trials will measure what’s known as “progression-free survival,” or the time it takes before tumors start growing again, but not whether patients live longer.

Proving that a drug extends survival is especially hard in cancer trials because patients don’t want to stay in a trial if their disease gets worse, or may want to add another experimental treatment. “In cancer, we’re probably not going to get a clean answer,” Woodcock said. Instead, the best evidence that cancer drugs are effective would be an increase in national survival rates over time, she said.

By law, the FDA has the authority to issue fines or even pull a drug off the market if a drugmaker doesn’t meet its post-marketing requirements. Yet the agency has never fined a company for missing a deadline, according to Woodcock.

“We would consider fines if we thought companies were simply dragging their feet, but we would have the burden to show they really weren’t trying, and it’d be an administrative thing that companies could contest,” said Woodcock.

Even when post-marketing studies belatedly confirm that drugs are dangerous, the agency doesn’t always pull them off the market. Consider Uloric, the gout treatment. Even though it consistently lowered uric acid blood levels, the FDA rejected it in 2005 and again in 2006, because trials linked it to cardiovascular problems. But a third study by the manufacturer, Takeda Pharmaceutical of Osaka, Japan, didn’t raise the same alarms. So the agency decided in 2009 to let the drug on the market, while asking Takeda for a post-marketing study of 6,000 patients to clarify the drug’s cardiovascular effects.

Takeda took more than eight years to complete the study. It found that patients on Uloric had a 22 percent higher risk of death from any cause and a 34 percent higher risk of heart-related deaths than patients taking allopurinol, a generic alternative. The FDA issued a public alert in November 2017, sharing the results of the trial, but left Uloric on the market.

Public Citizen has warned patients to stop taking Uloric. “There is no justification for using it,” said Carome. “If the results of the most recent study had been available prior to FDA approval, the FDA likely would have rejected the drug.”

FDA spokeswoman Walsh said it is “conducting a comprehensive evaluation of this safety issue and will update the public when we have new information.”

Takeda is working with the FDA to “conduct a comprehensive review,” spokeswoman Kara Hoeger said in an email. The company wants to ensure that “physicians have comprehensive and accurate information to make educated treatment decisions.” Thomas Moore, senior scientist of drug safety and policy at the Institute for Safe Medication Practices, warned that future post-marketing findings on Nuplazid could be similarly bleak. Uloric “is the story of [Nuplazid] but a few years down the pike,” he said.

Nevertheless, FDA Commissioner Gottlieb is forging ahead with more shortcuts. In May, he announced plans to approve gene therapies for hemophilia based on whether they increased the level of clotting proteins, without waiting for evidence of reduced bleeding.

Two years ago, a prescient Dr. Ellis Unger, FDA’s Director of the Office of Drug Evaluation, had warned against precisely this initiative. After Woodcock approved Exondys 51 in 2016, Unger wrote, “A gene therapy designed to produce a missing clotting factor could receive accelerated approval on the basis of a tiny yet inconsequential change in levels of the factor…The precedent set here could lead to the approval of drugs for rare diseases without substantial evidence of effectiveness.”

Gottlieb seems less worried than Unger.

“For some of these products, there’s going to be some uncertainty, even at the time of approval,” Gottlieb said when announcing the plan. “These products are initially being aimed at devastating diseases, many of which are fatal and lack available therapy. In these settings, we’ve traditionally been willing to accept more uncertainty to facilitate timely access to promising therapies.”

His decision pleased investors. That day, while biotechnology stocks overall fell, shares of hemophilia gene therapy manufacturers rose.

Caroline Chen covers health care for ProPublica. caroline.chen@propublica.org @carolineylchen 650-868-1213 Signal: 650-868-1213 https://www.propublica.org/article/fda-repays-industry-by-rushing-risky-drugs-to-market

When you ask anyone involved in drug R&D about pro-industry bias on the part of the FDA, they laugh. A company’s FDA interactions with respect to any drug clinical development program are difficult and challenging. That’s the way it has always been and that will never change. Furthermore, if you were to ask the CEOs of Pfizer, Merck, Lilly, etc., they would be more than happy to drop the “user fees” and have Congress fully fund the FDA via other funding mechanisms. That would remove any hint of FDA bias. But don’t hold your breath–“user fees” are forever.

John LaMattina was the president of Pfizer Global Research and Development in 2007 where he managed more than 13,000 scientists and professionals in the United States, Europe, and Asia.
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Screening mammography was touted to be another major leap in medical science to detect breast cancers at an earlier stage, which should help facilitate successful medication.

Contrary to that enthusiastic claim, a recent study of more than a million breast cancer patients revealed that not only was the breast cancer incidence not reduced significantly as advertised, screening mammograms lead to massive overdiagnosis of breast lump patients falsely classified as breast cancers requiring more aggressive treatments.

As everyone knows, aggressive treatment means expensive drugs and high octane professional fees, all needlessly compounding to the overall severity of the injury to the victims.

The researchers’ conclusion is not encouraging…

“Screening can result in both the benefit of a reduction in mortality and the harm of overdiagnosis. Our analysis suggests that whatever the mortality benefit, breast-cancer screening involved a substantial harm of excess detection of additional early-stage cancers that was not matched by a reduction in late-stage cancers. This imbalance indicates a considerable amount of overdiagnosis involving more than 1 million women in the past three decades — and, according to our best-guess estimate, more than 70,000 women in 2008 (accounting for 31% of all breast cancers diagnosed in women 40 years of age or older).

Over the same period, the rate of death from breast cancer decreased considerably. Among women 40 years of age or older, deaths from breast cancer decreased from 71 to 51 deaths per 100,000 women — a 28% decrease.6 This reduction in mortality is probably due to some combination of the effects of screening mammography and better treatment. Seven separate modeling exercises by the Cancer Intervention and Surveillance Modeling Network investigators provided a wide range of estimates for the relative contribution of each effect: screening mammography might be responsible for as little as 28% or as much as 65% of the observed reduction in mortality (the remainder being the effect of better treatment).13

Our data show that the true contribution of mammography to decreasing mortality must be at the low end of this range. They suggest that mammography has largely not met the first prerequisite for screening to reduce cancer-specific mortality — a reduction in the number of women who present with late-stage cancer. Because the absolute reduction in deaths (20 deaths per 100,000 women) is larger than the absolute reduction in the number of cases of late-stage cancer (8 cases per 100,000 women), the contribution of early detection to decreasing numbers of deaths must be small.

Furthermore, as noted by others,14 the small reduction in cases of late-stage cancer that has occurred has been confined to regional (largely node-positive) disease — a stage that can now often be treated successfully, with an expected 5-year survival rate of 85% among women 40 years of age or older.15,16 Unfortunately, however, the number of women in the United States who present with distant disease, only 25% of whom survive for 5 years,15 appears not to have been affected by screening.

Whereas the decrease in the rate of death from breast cancer was 28% among women 40 years of age or older, the concurrent rate decrease was 42% among women younger than 40 years of age.6 In other words, there was a larger relative reduction in mortality among women who were not exposed to screening mammography than among those who were exposed. We are left to conclude, as others have,17,18 that the good news in breast cancer — decreasing mortality — must largely be the result of improved treatment, not screening. Ironically, improvements in treatment tend to deteriorate the benefit of screening. As treatment of clinically detected disease (detected by means other than screening) improves, the benefit of screening diminishes. For example, since pneumonia can be treated successfully, no one would suggest that we screen for pneumonia.

Our finding of substantial overdiagnosis of breast cancer with the use of screening mammography in the United States replicates the findings of investigators in other countries (Table S5 in the Supplementary Appendix). Nevertheless, our analysis has several limitations. Overdiagnosis can never be directly observed and thus can only be inferred from that which is observed — reported incidence. Figure 1 and Figure 2 are based on unaltered,long-standing, carefully collected federal data that are generally considered to be incontrovertible. Table 1 and Table 2, however, are based on assumptions that warrant a more critical evaluation.

First, our results might be sensitive to the period (1976 through 1978) that we chose to obtain data for the baseline incidence of breast cancer (before mammography). If the period were expanded to begin with the first years of SEER data (i.e., 1973 through 1978), the baseline incidence of early-stage cancer would be slightly lower (0.9%) and the incidence of late-stage cancer would be slightly higher (1.4%). These changes offset each other and have a negligible effect on our estimates.

Second, our ability to remove the effect of hormone-replacement therapy (Fig. S1 in the Supplementary Appendix) is admittedly imprecise. Although there is general agreement that this effect had largely ceased by 2006, its onset is not as discrete. We chose to cap the incidence of each disease stage as far back as 1990. However, the pattern of regional disease (Figure 2) suggests that the bulk of the effect of hormone-replacement therapy probably began later, in the mid-1990s, such that our assumption probably overcorrects for the effect of hormone-replacement therapy.

Third, we were forced to make some assumptions about the pattern of the underlying incidence — the incidence that would have been observed in the absence of screening. The simplest approach was to assume that the underlying incidence was constant (the base case). In our best-guess estimate, however, we posited that the underlying incidence was that observed in the population of women without exposure to mammography; this underlying incidence was increasing at a rate of 0.25% per year. Our assumption of an increase of 0.5% per year (in the extreme and very extreme estimates) was admittedly arbitrary. It was twice the rate of increase observed among women younger than 40 years of age and was outside the 95% confidence interval. Perspective on the uncertainty about the underlying incidence, however, is provided in Figure 2. The finding of a stable rate of distant disease argues against dramatic changes in the underlying incidence of breast cancer.

Fourth, our best-guess estimate of the frequency of overdiagnosis — 31% of all breast cancers — did not distinguish between DCIS and invasive breast cancer. Our method did not allow us to disentangle the two. We did, however, estimate the frequency of overdiagnosis of invasive breast cancer under the assumption that all cases of DCIS were overdiagnosed. This analysis suggested that invasive disease accounted for about half the overdiagnoses shown in Table 2 and that about 20% of all invasive breast cancers were overdiagnosed; these findings replicate those of other studies.19

Finally, some investigators might point out that our best-guess estimate of the frequency of overdiagnosis — 31% — was based on the wrong denominator. Our denominator was the number of all diagnosed breast cancers. Many investigators would argue that because overdiagnosis is the result of screening, the correct denominator is screening-detected breast cancers. Unfortunately, because the SEER program does not collect data on the method of detection, we were unable to distinguish screening-detected from clinically detected cancers. Self-reported data from the National Health Interview Survey, however, suggest that approximately 60% of all breast cancers were detected by means of screening in the period from 2001 through 2003.20

Breast-cancer overdiagnosis is a complex and sometimes contentious issue. Ideally, reliable estimates about the magnitude of overdiagnosis would come from long-term follow-up after a randomized trial.21 Among the nine randomized trials of mammography, the lone example of this is the 15-year follow-up after the end of the Malmö Trial,22 which showed that about a quarter of mammographically detected cancers were overdiagnosed.23 Unfortunately, trials also provide a relatively narrow view involving one subgroup of patients, one research protocol, and one point in time. We are concerned that the trials — now generally three decades old — no longer provide relevant data on either the benefit with respect to reduced mortality (because treatment has improved) or the harm of overdiagnosis (because of enhancements in mammographic imaging and lower radiologic and pathological diagnostic thresholds).

Our investigation takes a different view, which might be considered the view from space. It does not involve a selected group of patients, a specific protocol, or a single point in time. Instead, it considers national data over a period of three decades and details what has actually happened since the introduction of screening mammography. There has been plenty of time for the surplus of diagnoses of early-stage cancer to translate into a reduction in diagnoses of late-stage cancer — thus eliminating concern about lead time.24 This broad view is the major strength of our study.

Our study raises serious questions about the value of screening mammography. It clarifies that the benefit of mortality reduction is probably smaller, and the harm of overdiagnosis probably larger, than has been previously recognized. And although no one can say with certainty which women have cancers that are overdiagnosed, there is certainty about what happens to them: they undergo surgery, radiation therapy, hormonal therapy for 5 years or more, chemotherapy, or (usually) a combination of these treatments for abnormalities that otherwise would not have caused illness. Proponents of screening should provide women with data from a randomized screening trial that reflects improvements in current therapy and includes strategies to mitigate overdiagnosis in the intervention group. Women should recognize that our study does not answer the question “Should I be screened for breast cancer?” However, they can rest assured that the question has more than one right answer.

http://www.nejm.org/doi/full/10.1056/NEJMoa1206809#t=articleDiscussion

This rarely publicized scientific research within the medical community itself debunk the constant assertion of QuackWatch.org that only mainstream medicine works. The evidences proving otherwise exist within their own infrastructure, and certainly

… it is not quackery to quote from this body of evidence to say that the medical priesthood is nothing but a profiteering enterprise which recognizes the sordid fact that curing diseases is anathema to its very own existence.

Now that the damage has already been done and admitted to be a case of overdiagnosis, can the people sue and ask for remuneration?

We can help our body cure every disease it is suffering from. We only need to understand the basic functions of our organs, and realize that the best antibiotic is not chemical drugs which the liver will have a hard time dealing with.

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Chemtrail Planes Caught in Action, Warn Population by Writing “Last Chance” Sky High

Commercial pilots are now gathering actual chemtrail operation evidence and some chemtrail pilots are writing their message up in the sky to warn the public to wake up now, or suffer the grave consequences later on.

Continue reading Chemtrail Planes Caught in Action, Warn Population by Writing “Last Chance” Sky High

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What This City Did With An Abandoned Walmart Is Absolutely Brilliant. You’ll Love It

You’ll find a Walmart store in most American towns and cities. These stores are almost always giant, taking up an average 2.5 football fields worth of space. So what happens when one of them closes? It’s an awful lot of space to just let sit there.

Officials in McAllen, Texas, were faced with this problem when their local Walmart shut down. Instead of letting the giant store sit vacant, they did something amazing. They transformed it into the largest single-floor public library in America.

Now this is the library of my dreams. And it get’s even better…

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After stripping out the old walls and ceiling, the developers opted for a very modern feel for the space.

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The library now boasts 16 public meeting spaces, 14 public study rooms, 64 computer labs, 10 children’s computer labs, and 2 genealogy computer labs.

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Of course there is also a cafe, a used book store, an auditorium, and self check-out stations. This next part makes it perfect…

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What’s more is that they host an incredible Farmers’ Market.

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Where you can get everything you need.

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They even set up shop indoors in the winter.

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And Nino’s RioPizza Gulino dishes out fresh handmade pizza made with ingredients from the market!

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Even the grounds look amazing. This has to be the coolest public library ever.

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I guess it’s true what they say: everything is bigger in Texas. Even the public libraries. I think it’s time for me to start packing my bags (and my library card).

Sources: Weburbanist, Viral Nova,  Facebook/McAllenFarmersMarket

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Sweden is Now Recycling 99 Percent of its Trash

It would serve Americans greatly to take a page out of Sweden’s book about recycling their waste.

The Scandinavian nation of Sweden has set a new precedent in the world of recycling its trash, with a near zero waste amount of 99 percent. Sweden was already ahead of the game back in 2012, when they were recycling 96 percent of their trash, but the three percent jump in just two years is quite impressive.

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Image credit: sweden.media

How does Sweden do it? They have an aggressive recycling policy, which goes in an order of importance: prevention, reuse, recycling, recycling alternatives, and as a last resort, disposal in landfill. As of 2014, only 1 percent of their waste ends up in a landfill.

Swedes understand that producing less waste to begin with is key to reducing the amount of trash that ends up being thrown away. Something as simple as using reusable containers for water and drinks can greatly reduce the amount of trash each person produces per year.

They have a very advanced system of trash separation which makes it easy to recycle nearly everything that’s thrown away.

Much of the left over waste is taken care of by using “recycling alternatives”, such as the Waste-to-Energy program, which is explained in this video:

Importing garbage for energy is good business for Sweden from Sweden on Vimeo.

While the “recycling alternative” remains controversial, it’s cleaner than drilling for oil or natural gas to burn in traditional power plants.

Sweden is so good at recycling its trash in fact, that it now has plans to import 800,000 tons of garbage from other countries in Europe in order to create heat for its citizens through its Waste-to-Energy program.

America should take note of this process considering we only recycle approximately 34 percent of the garbage we throw away.

h/t inhabitat.com

– See more at: http://livefreelivenatural.com/sweden-now-recycling-99-percent-trash-heres/#sthash.NwJ6xgJZ.dpuf

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Vaccines Hoax is Over, UK Docs Revealed

vaccine hoax is over

Andrew Baker ( FFN),– Freedom of Information Act in the UK filed by a doctor there has revealed 30 years of secret official documents showing that government experts have

1. Known the vaccines don’t work
2. Known they cause the diseases they are supposed to prevent
3. Known they are a hazard to children
4. Colluded to lie to the public
5. Worked to prevent safety studies

Continue reading Vaccines Hoax is Over, UK Docs Revealed

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Irish Orphans Used as Guinea Pig for Drugs

Revealed: Thousands of Irish orphans were used as ‘drug guinea pigs’

Published time: June 09, 2014 23:35 
Edited time: June 11, 2014 11:16

 

 

Over 2,000 care-home kids were secretly vaccinated against diphtheria in the 1930s in medical trials undertaken by international drugs giant Burroughs Wellcome, Irish media reveal. Among the testing sites was a recently discovered mass grave.

The medical records cited by the Irish Daily Mail show that some 2,051 children and babies across several Irish care homes may have been subjected to the practice.

Continue reading Irish Orphans Used as Guinea Pig for Drugs