KHN: Drugmakers Funnel Millions To Lawmakers; A Few Dozen Get $100,000-Plus

Before the midterm elections heated up, dozens of drugmakers had already poured about $12 million into the war chests of hundreds of members of Congress.

Since the beginning of last year, 34 lawmakers have each received more than $100,000 from pharmaceutical companies. Two of those — Reps. Greg Walden of Oregon, a key Republican committee chairman, and Kevin McCarthy of California, the House Republican majority leader — each received more than $200,000, a new Kaiser Health News database shows.

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As voters prepare to go to the polls, they can use a new database, “Pharma Cash to Congress,” tracking up to 10 years of pharmaceutical company contributions to any or all members of Congress, illuminating drugmakers’ efforts to influence legislation.

The drug industry ranks among lawmakers’ most generous patrons. In the past decade, Congress has received $79 million from 68 pharma political action committees, or PACs, run by employees of companies that make drugs treating everything from cancer to erectile dysfunction.

Drugmakers’ campaign contributions have reached record-breaking levels in recent years as skyrocketing drug prices have become a hot-button political issue. By June 30, 52 PACs funded by pharmaceutical companies and their trade organizations had given about $12 million to members of Congress for this election cycle. It is unclear whether drugmakers will top their previous 10-year record of $16 million, given during the 2016 election season.

While PAC contributions to candidates are limited, a larger donation frequently accompanies individual contributions from the company’s executives and other employees. It also sends a clear message to the recipient, campaign finance experts say, one they may remember when lobbyists come calling: There’s more where that came from.

The KHN analysis shows that pharmaceutical companies tend to play the field, giving to a wide swath of lawmakers on both sides of the aisle.

The drug industry favors power. Since the beginning of 2017, drugmakers contributed to 217 Republicans and 187 Democrats, giving only slightly more on average to Republicans, who currently control both chambers of Congress. This was also the case for Democrats during the 2010 election cycle, when they controlled Congress.

As with other industries, drugmakers tend to give more to lawmakers in leadership roles. For example, Rep. Paul Ryan, a Wisconsin Republican, became speaker of the House halfway through the 2016 election cycle, prompting drugmakers to pour $75,000 more into his war chest than they had the previous cycle.

Money also tends to flow to congressional committees with jurisdiction over pharmaceutical issues that can affect things like drug pricing and FDA approval. Walden, a nine-term Republican congressman, has watched his coffers swell with help from drugmaker PACs since he became chairman of the powerful House Committee on Energy and Commerce in early 2017.

With six months to go in the 2018 cycle, Walden had already raised an additional $71,000 over the 2016 cycle — or 11 times more than drugmakers gave him a decade ago.

Asked to comment on the increase in Walden’s contributions from drugmakers, Zach Hunter, his committee spokesman, called attention to Walden’s work to lower prescription drug prices and said “no member of Congress has done more” to end the opioid crisis.

Pharmaceutical company PACs also gave to dozens of other members of committees, such as the Senate Committee on Health, Education, Labor and Pensions. And they appear to target congressional districts that are home to their headquarters and other facilities.

The PAC for Purdue Pharma, the embattled opioid manufacturer, gave to only a handful of members this cycle. However, it focused much of its giving on lawmakers from North Carolina, its headquarters for manufacturing and technical operations.

This election cycle, 28 percent of lawmakers did not receive any contributions from pharmaceutical PACs.

Under federal law, corporations cannot donate directly to political candidates. Exploiting a common loophole, they instead set up PACs, funded by money collected from employees. Those PACs then donate to campaigns, which are free to spend that money as they wish on necessities like advertising or campaign events.

Campaign contributions tell only part of the story. Drugmakers also spend millions of dollars lobbying members of Congress directly and give to patient advocacy groups, which provide patients to testify on Capitol Hill and organize social media campaigns on drugmakers’ behalf.

A previous investigation by Kaiser Health News, “Pre$cription for Power,” examined charitable giving by top drugmakers and found that 14 of them donated a combined $116 million to patient advocacy groups in 2015 alone.

And like other industries, pharmaceutical companies wield their political power in ways veiled from the public, giving to “dark money” groups and super PACs — independent groups barred from directly donating to or coordinating with campaigns — bent on swaying lawmaking.

Brendan Fischer, who directs federal reform programs at the Campaign Legal Center, cautioned that a campaign contribution from a corporate PAC does not directly translate into a vote in the drugmaker’s favor.

“Contributions help keep the door open for company lobbyists,” he said.

KHN data editor Elizabeth Lucas contributed to this story.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

 

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Is the US setting the bar too low for new CF drug? Canada says it’s not worth it

From The Globe and Mail:

Canadian governments should not pay for a $250,000-a-year cystic fibrosis medication because it is not clear the drug actually improves patients’ health, according to a fresh review that has devastated some with the potentially fatal lung disease….

Screen Shot 2018-10-15 at 9.06.47 AMIn a report released on Thursday, the CADTH’s expert panel said its review of the Orkambi clinical trials and other studies found the drug produced only slight improvements for about one in four patients.

The report also said Orkambi’s Boston-based maker, Vertex Pharmaceuticals, would have to slash the drug’s price by more than 98 per cent to satisfy the agency’s value-for-money analysis.

“[Orkambi] is better than nothing. It’s better than placebo,” said Trevor Richter, director of the CADTH’s Common Drug Review, which oversees the review process for non-cancer medications. “But the benefit is really small. Not only is it small, but there’s a huge amount of uncertainty about what the actual size of that benefit is.”…

Vertex called the agency’s recommendation “deeply disappointing.”

Patients, who say the drug benefited them, are suing.

Mr. Richter of the CADTH said it is difficult but necessary sometimes to disappoint patients.

“We don’t enjoy delivering recommendations that are seen as negative,” he said. “In the end, we are an evidence-based review process. It’s rigorous and it’s transparent.”

Harvard study find that #immigrants’ #health #premiums exceed cost of care; Kaiser Health News explains

President Donald Trump has repeatedly condemned U.S. immigration policy, arguing that many immigrants pose a threat to the nation and drain U.S. resources. But a study released Monday about health insurance challenges the president’s portrayal.download

The study in the journal Health Affairs found that immigrants covered by private health insurance and their employers contributed nearly $25 billion more in premiums in 2014 than was spent on their care. Those in the country without legal status contributed nearly $8 billion toward the surplus.

In contrast, U.S.-born enrollees spent nearly $25 billion more than they paid for in premiums.

These findings surface as the Trump administration’s immigration policies — including a plan to tie migrants’ efforts to get permission for permanent residency to their use of federal benefit programs — have come under scrutiny.

Earlier studies also found that immigrants contribute more to Medicare than they receive in benefits, but the authors of this study say it is the first to look at the effect in private insurance plans.

Leah Zallman, assistant professor of medicine at Harvard Medical School and lead author of the study, said her findings allude to the potentially negative consequences that tighter immigration policies could have on the health care industry.

“I think in today’s era … there’s so much concern about immigrants and immigration really sort of draining our resources in the U.S.,” Zallman said. “This really points to the critical role that immigrants have in actually subsidizing and maintaining our current systems.”

Researchers calculated the financial contributions and expenses of enrollees and their employers using two surveys created by the federal government. Plans sold on the federal health law’s insurance exchanges were not included because they “differ from other private insurance in important ways and are unavailable to undocumented people,” the study authors noted.

Anyone born outside of the United States was categorized as an immigrant. However, the surveys did not ask non-citizens with private coverage about their legal status. Researchers used national data on undocumented immigrants to estimate how many people in the study group illegally resided in the country.

In 2014, immigrants and their employers contributed $88.7 billion in private insurance premiums, but spent only $64 billion for care, according to the study’s findings. Of that group, undocumented immigrants alone paid more than $17 billion to private insurers but used only $9.4 billion.

Native-born consumers paid $616 billion in premiums and received nearly $641 billion in insurers’ payments for care. They also consistently outspent immigrants across all age groups. Among enrollees 65 and older, the U.S.-born made a net contribution of nearly $10,000 more toward their care than those born overseas, according to the study.

The researchers reported that, on average, individual immigrants paid $1,123 more for premiums in 2014 than they received in insurance-covered care. U.S. natives instead cost insurers $163 on average.

Leighton Ku, director of the Center for Health Policy Research at George Washington University who was not involved in the study, said several factors contribute to immigrants’ low health care expenses. The group tends to be healthier and younger when they arrive in the United States. Cultural and language differences also hinder them from accessing care.

The study noted that immigrants’ health care expenditures increased the longer they remained in the country. But it added that since their premiums also increased at the same time, they continued to make a net contribution to their private health plans.

The findings come about a week after the Department of Homeland Security proposed redefining how it would determine “public charge,” a term used to describe a person likely to become dependent on the government for assistance. The proposal would make it harder for immigrants to live and work permanently in the U.S. if they receive certain types of federal assistance, such as Medicaid, food stamps and housing subsidies.

Trump has vowed to be tough on immigration standards. During his campaign, he berated U.S. health expenditures on immigrants, arguing that the U.S. spent $11 billion for care to people who were in the country without authorization, the study’s authors note.

But they point out that earlier research shows that immigrants have low rates of health care use and spending, compared with native residents. Their payments to private plans and Medicare in essence prop up care for patients who are U.S.-born, the authors say.

A study Zallman published earlier showed unauthorized immigrants contributed $35.1 billion more to Medicare from 2000 to 2011 than they used in services.

Benedic Ippolito, an economist at the American Enterprise Institute, cautioned using the study’s findings to draw conclusions on a large scale about immigrants and their role in health insurance. An estimated 20 percent of immigrants — including nearly half of the undocumented population — are uninsured, according to the study. Ippolito said the cost of their uncompensated care affects whether immigrants’ financial contributions actually lead to surpluses for health care overall.

“I would be careful about how much I extrapolate these results to a) other parts of the health insurance market and b) even further to what this means for immigration policy,” Ippolito said. “This paper alone does not tell us everything we need to know.”

Ku echoed the uncertainty. He said he is not certain how the Trump administration’s latest actions will affect immigrants enrolled in private insurance. Having a private plan may suggest they are employed with a certain income stability. However, if enough immigrants leave the insurance market, he added, it may have the unintended consequence of making health plans more expensive for everyone else.

“That does have the following implication that to the extent that we do things to suppress immigrants or make it harder for them to purchase insurance then in that case we may do harm to the citizens,” he said.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

 

Wednesday offers a burst of health #events in #Boston covering outbreaks, drug costs, AI and more

Wednesday 9/26 seems to be an extraordinary day for health and medicine events. Thanks to the calendar listing on   “Selected Lectures on Science and Engineering
in the Boston Area”

10-1p.  “Media in the Age of Contagions.”   A symposium.   HLS:  Wasserstein Hall, Milstein West (2019), 1585 Massachusetts Ave.   Details, Abstract, Registration.

Noon.  “U.S. Drug Prices: Why Are They So High?”   A panel discussion.   A webinar.   Details.   An on-demand video will be posted afterwards on the event website. A searchable transcript will be posted there a few days after the event.

12:15p.  “COMPACT: Childhood Obesity Modeling for Prevention and Community Transformation.”   Christina Economos.   Tufts:  Jaharis Center, Behrakis Auditorium.   Details.   This event will be streamed.

longwood map 21-5p.  “Sex Differences and the Brain.”   A symposium.   B&W:  Hale Bldg., 60 Fenwood Rd.  Details, Registration.

4p.  “Working with Post-Traumatic Medication Beliefs.”   Kathryn Kieran.   McLean Hospital:  Service Bldg, Pierce Hall.   Details.

5:30-8p.  “Artificial Intelligence in Healthcare: The Sooner the Better.”   Panel duscussion.   TBA.   Details, Registration.   This event will be live streamed.

7pm   “The Poison Squad.”   Deborah Blum.   Museum of Science:  Cahners Theater.   Details, Abstract.

 

From MIT’s Undark: More and More, New Drugs Clear the FDA With ‘Accelerated Approval’

Increasing reliance on this and other means of moving drugs quickly to market have many critics worried, given that drugmakers benefit most.

September 10, 2018 by Abigail Fagan & Mark Kaufman

On June 28, 2011, ten police cars descended upon the headquarters of the Food and Drug Administration. Scores of protesters carrying loudspeakers and donning pink shirts had attempted to enter the building, but were thwarted by the officers. One man held a sign that read: “My wife is not a statistic: Save Avastin.”

downloadAvastin was one of the world’s best-selling cancer drugs, first approved in 2004 to treat advanced colon cancer, with high expectations. The first drug of its kind, it was designed to block the blood supply of growing tumors, and it appeared to work well for colon cancer and lung cancer. Riding on a swell of optimism, the FDA decided in 2008 that Avastin could also be used to treat a certain type of advanced breast cancer — but just three years later, the agency seemed poised to reverse that decision.

Inside the building that June morning, a public hearing on that decision was being held. Some members of the audience shouted “Don’t take my drugs away!” Others came with photo albums in the hopes of showing the expert panel weighing the drug’s fate how the cancer drug had saved them from the ravages of breast cancer, and allowed them to live longer, fuller lives.

bhn deskThe pleas didn’t work. The panel concluded that Avastin didn’t improve chances for surviving breast cancer, and in fact, determined that the drug was so toxic — it sometimes caused high blood pressure, heart attacks, and ruptured intestines — that it could be more lethal than the cancer itself. Four and a half months later, the FDA officially rescinded the approval of Avastin for treating breast cancer. The FDA commissioner at the time, Margaret Hamburg, admitted that new evidence showed that the once-promising drug was not actually effective in treating breast cancer. “It is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit… that would justify those risks,” Hamburg said at the news briefing.

The anger and disappointment of the gathered patients was palpable, but the stunning reversal, and Hamburg’s own words, raised a troubling question: If there was no evidence that Avastin was effective against breast cancer — and even some evidence that it was explicitly harmful — why was it approved as a breast cancer treatment in the first place, and why was the company that made the drug, Genentech, permitted to market Avastin to doctors and breast cancer patients for the better part of three years?

It’s a question that cuts to the heart of a program that allows the FDA to approve drugs using a lower standard of evidence. Under what’s known as the Accelerated Approval Program, the FDA can reduce the bar for approval in cases where there is an unmet medical need for a serious condition. In such cases, a drug manufacturer need not show that the drug works. It only needs to demonstrate some reasonable expectation that the drug ought to work.

By definition, that’s a much more subjective threshold, but according to Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research, the benefits of accelerated approval more than justify the problems that might come with lowering standards of scientific evidence — particularly when desperate patients are willing to gamble on the additional risk. “It’s not unusual to have differences of opinions about accelerated approval because it’s more uncertain,” Woodcock said. “The patients are saying ‘we want to accept the tradeoffs, we’ll accept more uncertainty.’”

Today, the FDA is increasingly proactive in bringing drugs to market short of full approval and uses accelerated approval to get new drugs to people suffering from devastating diseases. Since 2003, more than 16 percent (66 of 404) of all new drugs were approved through the Accelerated Approval Program, and it seems to be a more popular option. Between 2003 and 2013, about three drugs were approved each year through this expedited route. But during each of the last three years (through 2016), that number has increased to more than seven drugs per year.



The FDA is candid about its commitment to expedited approval programs — in part to speed up what is often characterized as a notoriously drawn-out and bureaucratic approval process. The agency’s former head, Hamburg, wrote about the FDA’s intention of getting new drugs to people as “quickly” as possible, and the FDA’s new leader, doctor and cancer survivor Scott Gottlieb, bemoans the FDA’s slow-moving approval process. While a fellow at the conservative American Enterprise Institute in 2012, Gottlieb lamented the “increasingly unreasonable hunger for statistical certainty on the part of the FDA.” And at Gottlieb’s confirmation hearing last May, he rejected the idea that speeding up drug approvals would compromise their safety, calling it a “false dichotomy that it all boils down to a choice between speed and safety.”

But the increasing reliance on accelerated approval and other means of expediting drug approval have many critics worried — particularly given that the interests most readily served by fast-track approvals are those of the pharmaceutical industry. David Gortler, an associate professor of pharmacology at Georgetown University and a former FDA medical officer, is one such critic. He fears that the drive to get drugs out faster with weaker scientific evidence is already taking a toll — not just on consumers who are taking drugs that should never have been approved, but also on the agency’s credibility.

“I don’t really recognize the agency for which I once worked,” said Gortler, “because they’re making all these crazy decisions.”


The essential problem is that when it comes to drug approvals, speed and certainty are fundamentally at odds. It typically takes years of testing in large numbers of patients to determine if a drug provides a meaningful benefit — including improving an individual’s odds of survival. And it’s impossible to detect potential side effects until a sufficient number of patients have been monitored carefully, and for enough time, for such problems to truly surface. It’s extremely time-consuming to show, scientifically, that a drug really works — and to understand its risks.

But not all patients have the luxury of time. In the early 1980s, for example, an HIV infection meant certain death, as the virus devastated a person’s immune system, leaving them with wasting, sore-ridden bodies. Without drugs available to combat the virus, the afflicted were pushed toward desperate, ineffective treatments. Some tried cooking medicine themselves, while others heard stories of potent drugs and sought them out on black markets. None of it, of course, worked.

Responding to the crisis, the FDA began experimenting with what would formally be called accelerated approval. Instead of requiring ironclad evidence that a potential anti-HIV drug prolonged patients’ lives, the agency asked for indirect evidence that the drug was working as it was supposed to. In 1992, the anti-HIV drug ddC was approved because initial trials demonstrated that patients using it showed an increase in the number of a certain type of immune-system cells in their bloodstream. It wasn’t proof that the drug actually helped patients — the agency asked for a number of follow-up studies to establish that fact — but the consequences of the disease were so grave that the agency decided that it was worth the risk to approve ddC.

In this case, the gamble paid off. The drug worked. “We approved the AIDS drugs … and over time it came about that those were correct decisions and the epidemic was controlled,” Woodcock said. It also set a pattern for the future. Under certain circumstances — only having to do with serious diseases and unmet needs — the FDA can allow a drug to come to market with a lesser standard of evidence. Instead of proving that a drug prevents heart attacks, a pharmaceutical company might only need to show a reduction of fatty cholesterol molecules in patients’ bloodstreams. Instead of proving that a cancer drug extends lives, the company might have to show only that the chemotherapy delays tumor growth for a while. And instead of showing a direct benefit to a patient, an applicant might need only demonstrate that its drug meets a “surrogate endpoint” that suggests the drug is helping people who take it.

Using these surrogate endpoints saves time; it might take only weeks or months to show that a drug affects patients’ blood chemistry, whereas it takes years to gather enough data — and enough deaths — to determine whether a drug can actually extend a patient’s lifespan. The promise of surrogate endpoints is getting drugs to patients who are in desperate need of them quicker, but the downside is that there’s less careful testing of whether the drug actually works, or whether it kills patients instead of helping them.

“It is likely” said Vinay Prasad, a hematologist-oncologist at Oregon Health and Sciences University, “that many people are being treated with drugs that actually do not make them live longer or live better.”


In September 2016, the FDA approved the drug eteplirsen, designed to treat Duchenne muscular dystrophy (DMD), which primarily affects young boys. DMD is an invariably fatal disease that slowly destroys the muscles of its victims. None of the disease’s variants has a cure, although drug therapies like steroids can help slow muscle deterioration. Eteplirsen, however, is the first drug approved to target the root of the disease. Despite the huge expense — starting at around $300,000 per year — eteplirsen is the only real source of hope for children dying of DMD.

The root of the disease is a protein called dystrophin that is necessary for building muscle fibers; but those with DMD have a genetic mutation that interferes with the normal production of this protein. Eteplirsen can be used to specifically counter the effects of one of these mutations.

To speed up the approval process for struggling boys and hapless parents, the FDA put eteplirsen on the accelerated approval pathway. During the drug’s testing, the trials were too short to determine if the drug actually improved how long the boys lived, so “dystrophin production” was used as a surrogate endpoint. The study’s scientists reasoned that if they found increased levels of the protein, it was a good indication that the medication would ultimately improve the children’s condition.

As it was, evidence did suggest that eteplirsen increased the levels of dystrophin in patients’ muscles, but the increase was tiny — far below what would be expected to have any clinical effect. Scientists were baffled, in fact, by the miniscule quantity of dystrophin the drug produced.

“I find it difficult to conceive how a treatment effect of three parts per thousand could confer clinical benefit,” wrote Ellis Unger, the director of the FDA’s Office of New Drugs, and who oversaw eteplirsen’s scientific review. “If there were 10 inches of snow on a sidewalk that needed to be cleared, three parts per thousand would amount to 1/32nd of an inch.”

Unger wrote that a drug would need to increase dystrophin levels to around 10 percent of normal, healthy levels to even be considered “reasonably likely” to offer “measurable clinical benefit.” This means that even if dystrophin levels were 32 times higher than the trial results, there would still be big question marks about eteplirsen’s effectiveness.

Indeed, given that the drug didn’t even seem to meet the weakened standard of a surrogate endpoint, Unger and the other FDA scientists on the review panel wanted the FDA not to approve eteplirsen. Still, their recommendation was overruled by Janet Woodcock, who concluded the results met FDA effectiveness and safety standards for drugs on an accelerated pathway. (Two of the eteplirsen panel members resigned after this decision.) DMD patients across the country are now fighting with their insurance companies to get coverage for the expensive new drug.

“They may very well be paying $300,000 for some snake oil treatment,” says Gortler at Georgetown University. “It’s mean too, because these people are very desperate. They’ve been given a death sentence and they want to have hope.”


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Prasad also warns that the increasing reliance on surrogate endpoints risks eroding the overall standards of new drugs that are allowed to appear on the market. If the bar for approval becomes so low, he reasons, pharmaceutical companies aren’t incentivized to make any of them truly safe and effective. “We want A-plus drugs, not D-minus drugs. So why are we accepting it?”

Not everyone takes such a hard line on the risk-benefit calculations at the heart of accelerated approval processes. Mikkael Sekeres is an oncologist at the Cleveland Clinic who served on the FDA’s advisory committee for Avastin on whether or not it should be withdrawn. While approval for use of the drug in treating breast cancer was ultimately rescinded, Sekeres says the FDA is right to try certain drugs — based on surrogate endpoints — if a disease is bad enough. “If the risk of disease is awful, then [the FDA] might be willing to consider a drug with more risk than with a disease that isn’t as awful,” Sekeres said.

He pointed by way of another example to lymphoma where patients might survive only 10 years with the disease — a rather long disease course. Running a complete clinical experiment to see if a drug can prolong cancer patients’ survival might take 15 years, Sekeres noted, meaning many patients would be dead before they can ever try the drug.

“So you make an approval based upon a clinical maker,” he said. And if a drug does prove to be harmful, the FDA’s accelerated approval program is designed to pull the drug from use — just like the FDA did for Avastin. “It’s a demonstration that the system works when the FDA reserves its rights to recommend removing the drug from approval,” said Sekeres. “I think the evidence is working and the FDA is exercising its duty to protect the public.”


To be sure, the FDA emphasizes that accelerated approval is designed to help patients with no other options. “This pathway allows for flexibility in new drug approvals for serious diseases with no satisfactory therapies while meeting the appropriate standards for safety and effectiveness,” FDA spokesperson Sandy Walsh wrote in an email. “Accelerated approval recognizes that physicians and patients are generally willing to accept greater risks or side effects from products that treat life-threatening and severely-debilitating illnesses, than they would accept from products that treat less serious illnesses.”

As it stands, the FDA approved 86 cancer drugs in the 15 years prior to October 2017. Twenty-nine cancer drugs were granted accelerated approval in the same time frame, representing about a third of all cancer drug approvals. And cancer therapies are a substantial component of all drugs brought to market, accounting for nearly 22 percent in the last 15 years.

Of course, even under the best circumstances, Walsh noted, the accelerated approval process can lead to approvals that are later revoked. “These limitations are a reason accelerated approval is available only for a limited group of drugs,” Walsh said, including “those intended to treat serious or life-threatening illnesses when the drug is expected to provide a meaningful benefit over existing therapy.”

Companies (Sarepta included) that approve drugs based on a surrogate endpoint are still required to conduct clinical trials, called Phase 4 confirmatory trials, demonstrating that the medication provides the intended benefit, Walsh added.

Still, there is some evidence that this may well depend on the drug. The drug Mylotarg was originally granted accelerated approval in 2000 with a surrogate endpoint showing a decrease in patients’ leukemia. Following its approval, however, further trials revealed the drug was not only ineffective, but could also be lethal. So in 2001, the FDA issued a so-called black box warning — a notice appearing on a drug’s label that warns users of “life-threatening risks.” Nine years after that, in 2010, Pfizer withdrew the drug completely.

Despite this, Mylotarg is back. The FDA, designating a lower dose and new population for the drug, approved it to treat certain patients with acute myeloid leukemia. But the new approval still relied on surrogate endpoints, which critics say prioritizes speed over compelling proof. One of the Mylotarg clinical trials, for example, found that the drug increased event-free survival by nearly eight months, but did not impact overall survival at all.

“The problem with surrogate outcomes is they’re more convenient because you can observe them sooner, but it’s very, very easy to get a big difference in the surrogate outcomes that does not translate into a big difference in survival,” says Peter Thall, a biostatistician and expert in clinical trial design at the MD Anderson Cancer Center. “The whole game of saying ‘This is statistically significant’ is grossly misleading. This is done again and again and again in oncology.”

This is also what happened in the case of Avastin. The drug was brought to market for the treatment of colon cancer and then lung cancer specifically, and in both cases, there actually was clinical data showing the drug marginally extended patients’ lives. But the 2008 approval of Avastin for breast cancer didn’t have that sort of data, so the FDA put Avastin on the accelerated approval pathway. Early evidence showed that when Avastin was used in combination with the chemotherapy drug paclitaxel, patients experienced an improvement in progression-free cancer survival over those that took the chemotherapy drug alone. However, clinical tests on cancer patients didn’t show that breast cancer patients actually lived any longer overall. Rather, the surrogate endpoint “progression-free survival” only meant that patients lived longer with the tumor after treatment.

Patients taking Avastin did seem to do better on this particular measure, so the FDA took the gamble to let patients start taking the drug. But in this case, follow-up studies showed that the drug didn’t actually increase overall survival. What’s more, Avastin proved unacceptably toxic, including producing gastrointestinal perforations in some patients. The FDA rescinded the approval, much to the disappointment of scores of breast cancer patients who were convinced that Avastin had saved their lives.

The uncertainty that comes with a surrogate-endpoint-based approval is a huge problem when it comes to treating cancer, said Oregon Health and Sciences University’s Prasad. “If you look at big randomized studies in oncology over [the] last few decades, they used to look at survival more. But survival as the endpoint of randomized studies has fallen and it’s largely been replaced by surrogates like progression-free survival,” Prasad says.

What’s worse: These surrogate endpoints often don’t mean the patient benefits. Prasad and his colleague Chul Kim investigated drugs for 55 cancer indications approved by the FDA based upon surrogate endpoints and discovered that only about half of those drugs had any sort of proof that the surrogate endpoint really helped patients in any meaningful way. The analysis was published in the journal Mayo Clinic Proceedings in 2016. “For almost half of these established surrogates, there is no published study ever showing what their correlation is with survival or quality of life,” Prasad said. “We just can’t even find documentation.”

Kim, lead author on the report and an attending physician at MedStar Georgetown University Hospital admits to being surprised. “It was sobering to see,” he said. “I’d expect to see more high-level evidence to support the use of surrogate endpoints. Because progression-free survival and response rate have been used for a long time.”

This lack of proof creates a layer of uncertainty that is extremely hard to explain to patients, Prasad says. People with cancer come to him desperate to find a drug that will prolong their lives. When he explains that a drug was shown to slow tumor growth, patients immediately ask, “Does that mean I live longer?” Prasad simply can’t answer that. And thanks to surrogate endpoints, FDA approval of a cancer drug doesn’t quite mean that it is proven “effective” in the way that patients naturally think it is.

Nonetheless, accelerated approval is likely to become increasingly common, experts say, because patients, politicians, and pharmaceutical companies are all shouting for swifter drug approval. “There’s been an ongoing beating of the drum,” said Joseph Ross, an associate professor and physician at Yale University, “about the FDA needing to be faster,”

But Ross urges caution before the approval process is kicked into an even higher gear. “All evidence suggests that the FDA is reviewing and approving drugs faster than any other peer regulator in the world,” he said. “But we need to do more studies now to show what this means for safety and efficacy.”

About half of new drugs, Ross says, are now approved on standards that might look impressive in the laboratory but might not actually benefit patients. “These drugs are being approved on the basis of lab measures, but will they improve symptoms and mortality?” Ross asked. “We don’t know.”

That’s why Kim and other experts would like to see more study of the impacts of accelerated approval and surrogate endpoints overall. “If a drug is approved on a surrogate endpoint, we must do a follow-up study to make sure that it was not a false sign of efficacy,” Kim said.

“Cancer drugs can be toxic,” he added. “Without those hard outcomes, we may just cause harm to patients.”


This article was produced by students in the Science, Health & Environmental Reporting Program at the NYU school of journalism.

This article was originally published on Undark. Read the original article.

Politico on links between Medicare and #UMass #Med streamlined patient records program — Boston Boomer News

Politico story on Medicare and electronic medical records take us to UMass Med and it’s “Patient Ping” program. Normally when a patient like Pressley shows up in an ER, what follows is as confusing to the doctors as it is to the patient. Health records tend to be scattered through the many offices and hospitals…

via Politico on links between Medicare and #UMass #Med streamlined patient records program — Boston Boomer News

Once the “Red Sox hospital,” now a nursing home, Sancta Maria in Cambridge to close.

The Cambridge Chronicle has a nice story on the hospital’s history, along with some photos of the nuns who worked there.

CaptureShortly after its founding in 1948, Sancta Maria Hospital earned the nickname “the Red Sox hospital” because of the number of players who received care there. Initially located on Memorial Drive in Cambridge, a little more than a mile across the river from Fenway Park, the hospital provided a convenient place for treating players’ injuries and ailments.

The nuns on staff, members of the Daughters of Mary of the Immaculate Conception, would receive a call from a team doctor or trainer asking, “Is our room empty?”, according to a 1949 Boston Globe article. The nuns would start preparing “the Red Sox room,” described as a “pleasant, blue room with large open fireplace and cheery floral hangings.”