Latest Drugwonks' Blog
“So far, most new (cancer) drugs offer only marginal extensions of life and few cures. “
Now a look at the facts and where Pomalyst fits in the progress we are making against MM. Pomalyst was studied in people with MM who had no other options. As in, their MM was no longer responding to other drugs and they were going to die.
Clinical trials showed that median overall survival for people getting Pomalyst was 13.7 months.
Another study looked at response of patients who were no longer responding to other drugs and whose MM had already come back:
Clinical trials showed halfway into the study that nearly 50 percent of people receiving Pomalyst responded rapidly (as in the MM stopped progressing) and 78 percent had a median surival time of between 3-6 months. Patients receiving Pomalyst were seven times more likely to respond (and live) then those who received an old MM drug.
Now overall survival is the average time half of all patients in a study will live after treatment. So a median survival of 13.7 months means that after 13.7 months, 50% of people with that condition would be alive, and 50% would have passed away. Which also means that many people in the trials are living much longer than 13.7. Or in the other study, 3-6 months.
Several studies have shown that the median survival of people diagnosed with MM has gone from 3 years in 1997 to up to 20 years. The first MM drug was introduced in 1998. Two others were introduced in 2003 (Velcade) and Revlimid (2005) thereafter. W hen age is controlled for, that means an increasing number of people with MM can expect to have the same life expectancy as people who do not have the disease. And we can't measure the full impact of these drugs let alone Pomalyst in a precise manner.
But we can say that MM drugs have increased average life expectancy more rapidly among MM patients than it has average LE in the population as a whole.
And we can say that just as a few HIV drugs introduced over a 5 year period dramatically saved lives, so too have a handful of drugs for MM turned an incurable disease into a controllable condition in less than a decade. And these drugs work because they target specific disease mechanisms in patients for whom they work the best and offer the most hope. The averages are indicators of profound and rapid gains among more and more people.
If we had bought the story about marginal benefits 10 years ago and delayed and dragged out approval and use of other cancer drugs, where would we be today? If we accepted the arrogant assertion that "most new (cancer) drugs offer only marginal extensions of life and few cures.“ how may more people would be dead? Let me go out on a limb and say that while not all new products are useful and effective, the current effort to control health care costs is biased and shaped by this naysaying approach to innovation, an approach delays access to new medicines -- indeed an approach that subsidizes a industry of underachieving social scientists to study average cost effectiveness in an era of personalized medicine -- assures more people will die who did not have to or want to. Recently, the National Pharmaceuetical Council held a conference on The Myth of the Average Patient.. All well and good. But how about a conference on what CER will cost people seeking better medicines for cancer and Alzheimer's in terms of lives saved. My late colleague John Vernon and I did a lot of work in this area but somehow the "stakeholders" always ignore the impact of adding CER to the rate of innovation and the number of lives saved. Why is industry and patient groups silent about the impact of CER on medical progress? What gives?
Finally, why does it take so long to conduct clinical studies. In both of the trials mentioned above, response was immediate and highly effective. (Less than 6 months in most cases). Can't we find other ways to confirm what works and what doesn't? Here's Eric Topol on this important topic..
We have this big thing about evidence-based medicine and, of course, the sanctimonious randomized, placebo-controlled clinical trial. Well, that's great if one can do that, but often we're talking about needing thousands, if not tens of thousands, of patients for these types of clinical trials. And things are changing so fast with respect to medicine and, for example, genomically guided interventions that it's going to become increasingly difficult to justify these very large clinical trials.
We are not just standing in the way of medical progress, we are putting up obstacles based on outdated science and sanctimony.
Herding Katz.
The departure of Rusty Katz as FDA’s Director of the Neurology Products Division is an inflection point in the agency’s 21st century direction. Will his replacement continue his philosophy that the FDA must be a partner in innovation – or will political considerations turn back the clock?
Following Katz at FDA is an important analysis of the situation.
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From the pages of the Des Moines Register (and hello Senator Grassley):
Changes to Part D won't save Medicare
By: Peter Pitts
With a debt-ceiling showdown just around the corner, Republican lawmakers are insisting upon more government spending cuts in exchange for raising the country’s borrowing limit.
President Obama says the debt ceiling shouldn’t be used as a negotiating tool. But it’s inevitable that additional cuts will be seriously considered. And, unfortunately, lawmakers are likely to take aim at Medicare Part D, the highly successful prescription drug benefit.
This approach is misguided. Cuts to Medicare Part D would have devastating consequences for seniors and taxpayers.
Created in 2006, Medicare Part D has helped ensure that America’s seniors have access to prescription drugs. Today, nearly 47 million Americans are eligible for Part D.
The program was built to rely on market mechanisms. Under Part D, seniors choose from a wide variety of drug coverage plans — in fact, there are now over 1,000 different plans available across the country. With so many insurers competing for seniors’ business, they have a strong incentive to keep costs low and benefits generous.
This fierce competition has kept expenses down for both seniors and the government. Overall, Part D has cost $435 billion, or 43 percent less than original estimates predicted — practically unheard of for a government program.
Part D monthly premiums will again average just $30 in 2013, according to officials at the U.S. Department of Health and Human Services. That number has held basically steady for four years, and premiums are up only 2.5 percent since 2006.
Part D rates are even more impressive when compared to what is happening in the regular health insurance market. The typical premium for an employer-sponsored family health plan rose 4 percent from 2011 to 2012 and increased 9 percent the year before, according to the Kaiser Family Foundation.
Seniors, moreover, are pleased with their Part D coverage. A new poll sponsored by Medicare Today found that 90 percent of enrollees are satisfied — up 12 points from 78 percent in 2006.
Still, many Democrats are willing to compromise this highly successful program. Their proposal would require drug companies to pay a so-called “rebate” to the government for every medication sold to a Medicare Part D participant who also qualifies for Medicaid, the government health program for the poor. There are about six million of these dual-eligible seniors.
The Obama administration believes that its plan to overhaul Medicare spending will save nearly $600 billion, with 42 percent of those savings coming from the Part D drug rebates.
But this scheme won’t work the way the president intends. It will drive up health care costs for a large portion of Medicare beneficiaries.
Just look at what is already happening in our Medicaid program. Drug companies are required by law to sell their wares to Medicaid at below-market prices, and consequently they have been forced to raise prices elsewhere. In other words, the proposed Part D rebate program would effectively levy a new tax on every senior who is not eligible for Medicaid.
Indeed, two independent studies have estimated that the rebate plan will raise premiums for traditional Medicare enrollees by 20 to 50 percent.
Higher premiums are a big concern for most Part D beneficiaries. According to the Medicare Today poll, 84 percent of enrollees were worried that a Part D restructuring would increase their out-of-pocket drug costs, while 53 percent were afraid it would cause them to cut back or stop taking their medicines altogether.
Our government health programs are still in serious need of comprehensive reform. Unfortunately, the president continues to attack the very part of the system that is most financially sound. Changes to Medicare Part D will raise only minimal revenue — at the expense of seniors.
Sins of omission are seldom fun, and (per Health Care’s Trick Coin, NYT, 2/3/13), Ben Goldacre makes a number of serious mistakes – specifically the claim that the Clinicaltrials.gov registration requirement in FDAAA isn't implemented and that only full transparency/publication of clinical trial will address the issue. As the former senior government official in charge of clinicaltrials.gov, it’s important to look at the facts – and the numbers.
In 2000, the National Institutes of Health (NIH) launched ClinicalTrials.gov to provide public access to information on clinical studies. Although it initially contained information primarily on NIH-funded research, it has been expanded to include both publicly and privately supported clinical research.
Since the launch of the site, it has been enhanced to significantly increase data sharing. The ClinicalTrials.gov database includes information on nearly 140,000 clinical trials in all 50 states and 182 countries.
Is anyone accessing this wealth of information? Yes! The NIH reported last year that ClinicalTrials.gov “receives more than 95 million page views per month and 60,000 unique visitors daily.
Facts do not cease to exist because they are ignored. Mr. Goldacre should realize that reality, although sometimes inconvenient to ones argument, remains reality.
Great BioCentury lead article by Steve Usdin, Debating Limited Use.
Usdin writes:
FDA is asking the public to consider whether it should supplement the current all-or-nothing approval structure with a system that would couple approval of selected new drugs with measures designed to discourage off-label use.
The agency says it could approve drugs for conditions such as antibiotic-resistant infections and life-threatening obesity based on small, fast trials if it were confident use would be limited to well-defined populations.
There is little controversy about approving drugs based on relatively small studies that demonstrate high levels of efficacy in tightly targeted populations. But FDA’s suggestion that it could work with physicians and payers to limit use of a marketed drug in the absence of documented safety concerns is controversial.
To say the least.
Patient and medical groups support the concept of a limited-use pathway, and the President’s Council of Advisors on Science and Technology (PCAST) has endorsed the idea. PCAST’s recommendation to create a Special Medical Use (SMU) pathway was drafted in close consultation with senior FDA officials and reflects the agency’s thinking.
But, whether or not you believe the FDA has the legal authority for a “new” pathway, Janet Woodcock nails the problem dead on:
“We can indicate things for small populations, but often we are very concerned there might be a temptation to use them much more broadly.”
There are many important issues, let’s discuss two.
First – does the FDA have the authority, the resources, and the desire to direct the practice of medicine? Can the agency really do anything other than suggest, via labeling, how physicians should prescribe approved medicines? No doubt they can deter pharmaceutical companies from detailing or even discussing off-label use via prior agreement (and Caronia notwithstanding). Whether or not doctors are “tempted,” however, is another matter entirely. Is the FDA going to “ban” certain scientific publications or conference presentations? Is the FDA going to add a new tenet to the Hippocratic oath, “First do no reading?”
It’s a slippery slope indeed.
Woodcock added that FDA is not seeking to ban off-label prescribing of drugs approved through a new limited use pathway. The agency is interested in exploring whether payers might play a role in reducing inappropriate use, she said.
More power to the payers? Is that something we want?
Next is the issue of whether such expedited approval pathways are in the best interests of the sponsor. While there’s no doubt getting new treatments for serious and life-threatening diseases to market more swiftly is a good thing, is the threat of having a product license revoked after a “test” period in the sponsor’s best interest? Isn’t it a penny-wise, pound-foolish proposition? It depends. What is certain is that such decisions should not be driven by financial considerations of biotech venture capitalists or the panjandrums of Wall Street.
Naïve? Perhaps -- but none-the-less disturbing.
Is FDA PCAST-ing it’s net too wide?
Whenever there is authority, there is a natural inclination to disobedience.
-- Thomas Haliburton
A group of six Congressional Republicans sent a letter to HHS's Health Resources and Services Administration seeking details on the agency's audits of the eligibility of healthcare entities for the 340B drug discount program. The program requires manufacturers to give deep discounts on outpatient drugs to hospitals and clinics that bear the brunt of providing healthcare to low income and other special populations.
HRSA began the audits in FY12 after a 2011 report from the Government Accountability Office said HRSA's oversight of the 340B program was "inadequate to provide reasonable assurance that covered entities and drug manufacturers are in compliance" with the program's requirements. According to the letter, during 2012 HRSA decertified about 250 entities from the 340B program. The agency said it recertified more than 3,800 entities during the same time period.
The lawmakers are seeking information on audits that HRSA is currently conducting. The lawmakers also are seeking information on the decertified entities, including whether the agency plans to take legal action or recoup any ineligible 340B discounts.
The letter was sent by Sens. Chuck Grassley (R-Iowa), Lamar Alexander (R-Tenn.), Orrin Hatch (R-Utah) and Michael Enzi (R-Wyo.), as well as Reps. Joe Pitts (R-Pa.) and Bill Cassidy (R-La.). The lawmakers asked for a written response by Feb. 14. HRSA said it is working on a response.
Clearly, the practice of medicine, perhaps better described as the delivery of healthcare, is undergoing a radical, permanent change, at least for the foreseeable future. After all, we are only a few weeks into the first year of ObamaCare, and already HHC, one of the largest hospital corporations in the country, has decided to hold their physician employees financially responsible for the mandatory changes outlined by CMS. The complexity of these changes makes their adoption into current practice a daunting task for many physicians.
The simple fact is, that the future of medicine looks very different than it did when many of today’s doctors started medical school, even for those who have graduated in recent years. For those who entered the field to treat patients, cure disease and make a real difference in the lives of others, the current tasks that consume much of their time and energy are carrying them further and further away from that goal. The optimists in the field would like to believe that pay-for-performance is simply a resetting of the status quo, which will take considerable time and effort, but ultimately benefit our profession and our patients in the long term.
I am hesitant to agree with this view for two reasons, among others. First, I believe that many physicians are already at or near capacity in terms of their ability to deliver care, both in terms of organizational resources, and personal time and energy. Many individual and small-group practices simply do not have the resources to understand and implement the constantly changing mandates from CMS. Therefore, when you hand them a forever evolving checklist of arbitrary measures that they must follow in order to be reimbursed properly, you only increase confusion and frustration, and do little to impact productivity or foster a system that delivers better care.
Secondly, for any physician who sees their reimbursement cut by providing “sub-optimal care”, as deemed by CMS, what is to stop them from refusing to serve their sickest, most chronically ill and frequently hospitalized patients? In so doing, they raise the “quality” of care they provide, and lower the cost at the same time (they will not be responsible for those sick patients when CMS evaluates them the next year). Such a reaction to pay-for-performance would only further accelerate a current trend in medicine, which is seeing many physicians refuse to accept new Medicare patients.
It is impossible to forecast how pay-for-performance will ultimately impact the quality of care we provide, and the cost at which we do so. But one thing is certain; the job of physicians providing that care becomes more difficult every day.
Read the full piece here.
Small is Big.
Bob Temple said he "would like to see more" comparative effectiveness trials for symptomatic treatments to help identify potential responders. In particular, Temple said trials that randomize non-responders to a drug to receive both that drug and an alternative drug have "a lot of potential" but are almost never done.
"For example, you could take people who don't respond to a migraine drug and randomize them back to a new migraine drug, the old migraine drug the one they didn't respond to, and a placebo. If it's true that there are individual differences that are important, then the new drug ought to be able to show its advantage over the drug that didn't work," he wrote in a post on FDA's From a Clinical Perspective blog.
When asked whether institutional review boards (IRBs) would approve such trials, Temple said there is no ethical issue in an informed patient. He added that such trials would not be done for indications where "not working would be dangerous."
This seems to jive with what Dr. Joe Selby (PCORI’s executive director) told me the other day – that he believes PCORI should focus on funding “narrow” clinical trials aimed at smaller, more targeted populations, that PCORI's mission is to ensure that CER helps to advance the cause of personalized medicine and “the right treatment for the right patient at the right time.” Bravo.
If Joe Selby can be the Good Witch of Comparative Effectiveness Research, so much the better. I think he’d look lovely in ruby slippers.
As would Bob Temple.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
