Latest Drugwonks' Blog
If the earth were a single state, Istanbul would be its capital.
-- Napoleon Bonaparte
I’ve just returned from the World Cancer Leaders’ Summit in Istanbul. (The event was held in partnership with the International Agency for Research on Cancer, the International Atomic Energy Agency (IAEA), and the World Health Organization.) It was a Turkish delight in more ways than one.
I had the opportunity to talk about the value of quality as it pertains to access. Beyond discussing bioequivalence, biosimilarity, and the many and varied issues pertaining to 21st century pharamcovigilance, my major points were that (1) the most expensive drug is the one that doesn’t work and, (2) broader access to poor quality medicines is not a public health victory.
A key learning for me was that, when it comes to “the market” and “society" -- the market is society. That’s important to remember whether the debate is about access in the Developing World or price/value in the First World. We are all in this together.
During my session’s Q&A a representative from India accused me of slamming generic drugs. I told him that he was hearing what he wanted to hear. I reiterated that generic drugs play a crucial role in access to healthcare around the world – but that quality is a non-negotiable variable for all drugs (both innovator and generic). I reminded him about what I’d said no more that 90 seconds earlier about the USFDA’s new Super Office of Pharmaceutical Quality – that we must approach the issue with “one quality standard” for all medicines.
After all, per the Journal of Infection (2008;56:35-9), “Nothing is more expensive that treatment failure.” In the 21st Century, pharmacovigilance must be about ensuring predictable patient outcomes.
The Indian gentleman’s question highlights an important problem – what happens when your desires do not match the facts? The answer is that we have to listen with an open mind, carefully, and respectfully. We all have to enlarge our circle of policy colleagues. I’m pleased to report that he and I had a long and productive chat afterwards.
The theme of the event was, “Effective international collaboration … across country borders, across disease groups and, through public private partnerships.” It's a small world after all and, at least for a few days, Istanbul was indeed it’s capital.
Oncologists are supposed to treat cancer patients. But some have decided instead to set themselves up as judges of what patients' lives are worth.
This type of bean-counting ought to be abhorrent to anyone who calls himself a physician.
A recent article in JAMA Oncology is emblematic of this strain of thinking. The piece employs a "value framework" endorsed by the American Society of Clinical Oncologists to determine what a new drug "should" cost. Once approved by the FDA, the drug in question, necitumumab, will be the first of its kind to treat stage IV squamous non-small-cell lung cancer.
The lead author of the article, Daniel Goldstein, noted that adding necitumumab to the standard combination of drugs for such patients "only" adds about two months to patients' life, on average. As a result, he calculates, necitumumab should cost $600 a month.
Put another way, Goldstein believes that each extra day of life is worth, at most, $20. About the same price as a new toaster.
Goldstein's morbid conclusion demonstrates the callousness of ASCO's value framework, which seeks to derive "appropriate" drug prices from their average effect on longevity. In the process, the framework marginalizes the value of life.
Goldstein notes that "[t]here is a desperate need to find appropriate prices for new treatments while maintaining incentives to drive game-changing innovations." Yet his approach would whittle away payments for the hardest to treat cancers and for patients who have had no real advances in care for decades.
Necitumumab is not just another drug. As Nick Thatcher, the lead investigator for the necitumumab clinical trials, observed: "I think it's important to remember we're dealing with squamous cell lung cancer," which has proved notoriously difficult to treat. "It's the first time," he notes, "that we've seen benefit in this group of patients over the last 20 or 25 years." In that context, demonstrating any effectiveness at all counts as a breakthrough.
History indicates that more profound breakthroughs will follow, as researchers build on each incremental advance. The first anti-AIDS treatments added "only" two months of life in 1987. By 2006, a combination of new drugs—tailored to the particular biology of the patients—added 15 years of life. The value framework doesn't account for increasing medical progress over time.
Moreover, the value framework does not measure the value of living longer from the patient perspective. The five-year survival rate for those diagnosed with this form and stage of lung cancer is 1 percent. Isn't every extra day with loved ones—and beating cancer—worth more than $20?
Goldstein's conclusion—that many oncology drugs in clinical practice in the United States would fare poorly in cost-effectiveness analyses—could be applied to lung cancer treatment prices as a whole.
Since 1973, the average survival generated by any type of chemotherapy is 1.7 months. The average cost of treating lung cancer patients in the last year of life is $94,000. Drugs are about 20 percent of that spending. Why not let people die 1.7 months sooner and save the money?
When insurance companies try to control costs by restricting access to treatments, they are rightly lambasted for it. Doctors who seek to determine which drugs are worth paying for are no better.
We would not countenance paying more to extend the life of a rich man than a poor one, whatever the difference in their economic "value." Nor would we deem the life of a mother of five more worth saving than that of a childless woman, without a family to mourn her passing. But it is no more acceptable to average the social value of their lives in deciding whether it's worth it to treat them.
A cynic, it is said, knows the price of everything and the value of nothing. By this measure, ASCO's framework is cynical in the extreme. The only framework worth defending is one that says life is too precious to put a price on it.
Prescription drug plan is bad medicine for N.J. economy
White House contenders want to address – but don't understand – prescription drugs prices. The Center for American Progress has a plan. A bad one. The CAP plan would effectively turn the U.S. government into the world's biggest intellectual property thief, thus gutting pharmaceutical innovation and crippling New Jersey's economy.
New medications are expensive to develop. On average, it costs $2.6 billion and it takes a decade to bring a new medication successfully to market.
One of the reasons the process is so expensive is that most potentially promising compounds don't pan out. The vast majority of compounds never make it from the lab to the clinical trial stage, and the FDA approves only 12 percent of those that do.
Only a small percentage of approved medications ever recoup their development costs. Pharmaceutical companies have to set prices to cover the costs of both the occasional successes and the many, many, many failures that go along with them.
CAP's 45-page report ignores this reality and offers to lower drug prices by stripping pharmaceutical companies of their intellectual property. The federal government, CAP says, has the authority to license patents to knock-off generic manufacturers any time it deems brand-name drug prices are too high.
The authority for this heist is supposedly a 1980 federal law known as the Bayh-Dole Act, which ushered in a Golden Age of pharmaceutical innovation by shoring up intellectual property rights.
One provision of Bayh-Dole holds that the government retains so-called "march-in" rights to license a patent when its owner fails to take "effective steps to achieve practical application of the subject invention." In other words, if a patent is languishing unused, the feds can license it to encourage development.
CAP evidently believes that a high price tag constitutes a failure to take "effective steps to achieve practical application" – and is therefore grounds for the feds to seize a patent and license it to others.
Who decides what price is too high? Why, an all-powerful new government panel housed in the Department of Health and Human Services, of course. It's supposed to set a range for drug prices, and any drug priced more than 20 percent above this range is subject to patent seizure.
This interpretation of Bayh-Dole is the antithesis of what the authors sought. The law empowered innovators by protecting the work of university researchers, small businesses and nonprofits that incorporated basic concepts that had previously been discovered via federally funded research.
The bulk of biopharmaceutical innovation comes from private industry, which spends more than $51 billion annually to develop new drugs. These investments will simply stop if government has the authority to seize the patents of innovators any time they don't meet a government-set price.
Similar price-capping schemes in Europe, once an industry leader, essentially capped innovation and jobs. In the mid-1980s, Europe spent 24 percent more on research and development than firms did in the United States. As price caps took effect, by 2004 European development dropped 15 percent. Between 2001 and 2009, more than 60 percent of drug patents went to U.S.-based companies. In 2012, the U.S. biotech industry employed 100,000 people – twice as many as in all of Europe. Alas, as John Adams quipped, "Facts are pesky things."
As a major hub for the biopharmaceutical industry, New Jersey will bear the brunt of the CAP plan's job-killing regulations. Over 70,000 Garden Staters work for biopharmaceutical firms. Industry spending supports another 250,000 jobs in other sectors. All told, drug firms add $87 billion to New Jersey's economic output.
Government-sanctioned patent theft will lead to massive investment cuts and job losses in New Jersey. More worryingly, CAP's caps on drug prices would prevent the development of new medicines. Candidates embracing this approach pose a threat to our health.
Peter J. Pitts, a former FDA Associate Commissioner, is the president and co-founder of the Center for Medicine in the Public Interest.
Medicines aren’t priced in a vacuum. Pricing decisions are based on numerous meetings and tough negotiations between manufacturers and payers over a long period of time – often years before the FDA approves a product. In fact, many product programs are stopped or altered well before Phase III trials depending on these conversations.
So, when you hear about a new medicine and payers are complaining about the price, it’s (at best) disingenuous, but they get away with it. Why? Because manufacturers are uncomfortable calling out the insurance companies and PBMs with whom they must do business. The reverse is untrue in the extreme. And “disingenuous” is a polite way to say something else.
A new study from the IMS Institute for Healthcare Informatics puts some hard numbers behind the debate. And it’s about time.
As the report’s executive summary reports:
Price levels for pharmaceuticals in the U.S. market are often reported to the public based on list prices, and therefore do not reflect the series of adjustments that occur throughout the healthcare system and ultimately determine who pays what for medicines.
The purpose of this healthcare brief is to draw specific attention to previously published research from the IMS Institute which highlights not only the visible aspects of price increases, but also the less visible off-invoice discounts, rebates, coupons, and other price concessions to payers that often substantially offset these changes in list price. By bringing context and perspective to the complex interplay of factors that determine the level of price changes for branded medicines we hope to better inform discussions of the issues.
… Our analysis shows that branded pharmaceuticals raised invoice prices on average 13.5% in 2014, but on a net basis, after all of the concessions are adjusted for, the increase was 5.5%. This level of net price increases is notable for being the lowest of the past five years and has occurred even as invoice price increases have accelerated.
It’s time for everyone to debate the facts.
The complete report can be found here. It’s an important read at an important time.
Much ado about PCSK9 inhibitor patient assistance programs that requires users to share rights to their personal health information. Is this a legitimate quid pro quo? That’s a tough question – but not the most important one.
The foundational question is, why do companies want this information? Because it has valuable public health applications. Cumulative, de-identified real world data will provide the company with outcomes intelligence that can be shared with payers, physicians, and the scientific community. For payers and physicians, it will help better define what subset of patients with high cholesterol should receive Repatha as first line therapy, avoiding a costly (both in terms of dollars and cardiovascular health) “fail first” step-therapy scenario. And the information will allow researchers to better focus their efforts on expanding our understanding of the PCSK9 universe and the potential development of companion diagnostics.
All good reasons to have patients share their data. But should it be an “either/or” proposition? It needn’t be. Why not make such data sharing voluntary? Let patients know that by sharing their personal information they are helping “people like them” get diagnosed more directly and achieve better health results more rapidly. People want to do the right thing – but they have to understand why and how. Under this scenario the innovative biopharmaceutical industry can be the facilitators of better, more cost-efficient outcomes and be hailed as healthcare heroes.
Which is a lot better than what they’re currently being called.
Here's the knock-out blow against the lies and mis-statements regarding the 'unsustainable' cost of of new drugs"
"As costs have risen, many insurers have responded by increasing cost sharing for specialized therapies as part of their pharmaceutical insurance design. For example, CMS allows Part D plans to create a “formulary tier” specifically for drugs costing $600 or more per month. About 90% of plans use this tier and among these plans, more than half require patients to pay 25% or more of costs. Co-insurance for specialty drugs, which are taken by the sickest 3% of patients, can be as high as 50%.
This design means that the sickest patients also take the largest financial hits; a form of “double jeopardy.” However, this has primarily led to outrage against manufacturers rather than payers. For example, oncologists have criticized manufacturers for high prices because their patients cannot afford treatment. This is somewhat ironic since, as the General Accounting Office noted in July, cancer centers with higher markups on cancer drugs prescribe more of them, a practice partially enabled by the federal government’s 340B drug pricing program intended to provide discounted drugs to lower income patients. In addition, other forms of health care are equally, if not more expensive – such as ICU care – yet there appears to be comparably less concern over these costs. Perhaps the reason is that ICU care – which often costs approximately $4,000 per day – is often fully covered (as it should be), whereas specialty treatments remain only partially covered.
The reality is that less generous coverage of specialty drugs may punish the sickest patients and is not consistent with basic tenets of insurance, which are designed to cover rare but expensive events."
I just returned from Kaohsiung, where I was pleased to keynote the Taiwan Pharmacy International Collaboration Center’s Generic Equivalency and Biosimilarity conference.
Of the many excellent presentations from global experts, one of the most interesting was by Churn-Shiouh Gau, the Chief Executive Director of the Taiwanese Center for Drug Evaluation at National Taiwan University. She spoke on the current state of affairs of biosimilar regulation – and her talk generated some tough and specific questions.
For example – should Taiwan approve a biosimilar is the originator product hasn’t been approved. (For example, Remicaide isn’t an approved therapy in Taiwan – and there are already a few biosimialrs on the market in many other places – such as the EU.) Her view was “no.”
Also, should Taiwan approve a biosimilar that isn’t approved for use in its country of manufacture? Following the theory that what’s good for the goose is good for the gander, why should one country take a risk on a product (especially ones so new and complicated as biosimilars) that hasn’t been deemed safe and effective in its native land? Her view was, “no.”
Representatives of the Taiwan FDA (a First World Regulatory body) weighed in with many comments and caveats. Clearly questions such as these need to be addressed as seriously as those concerning biosimilar review pathways.
Voltaire said, “Judge a man by his questions rather than by his answers.” And the same can be said of medicines regulators. But we need to ask the right ones or we fall into the trap that Thomas Pynchon warns about when he writes, ““If they can get you asking the wrong questions, they don't have to worry about answers.”
“They” can broadly be defined as those focusing on biosimilars exclusively as a cost-saving mechanism. Safety and quality must always drive the regulatory discussion.
In talking about Opdivo, the new drug for people with advanced lung cancer that can add up to 2 years of life, Bach asserts:
"Federal law prevents the maker of nivolumab (Bristol-Myers Squibb) from providing assistance to patients who cannot afford the treatment. Programs such as Genentech's for Avastin, in which beneficiaries receive the drug free once they have spent a certain amount in a calendar year, are rare."
Untrue. Companies can't provide assistance directly but it can do so through 3rd party foundations and do so regularly. BMS provides an incredible amount of support to patients which frankly is provided because insurers don't cover the cost of the entire drug though it saves them money and improves patient lives better than stuff like surgery (which insurers cover completely). But in Bach's warped world, this is fine.
Then he proclaims that the only way to measure value is to see how much a new medicine or technology adds to a health plan's budget. Let's set aside the fact that most health care spending increases are the result of an increase in the use of other services and Bach never scrutinizes that. More important, new medicines almost always over time reduce the use of other services and contribute to at least half the increase productivity and longevity.
Bach claims that new medicines are no more effective than old medicines because they don't add any more average survival. Really? If that's the case than, how has cancer survivorship and life expectancy steadily increased over the past 20 years. Perhaps what he is say is that the additional increment of average survival (which ignores genomic variation) is not worth say $100000. But that ignores the fact that treatments are targeted to smaller populations that have fewer options than previous generations. Unfortunately, high prices are partially a result of investing the same amount of time and money on tinier groups of cancer patients. Bach knows better. After all, one of his co-authors in the paper he cites in his NEJM oral hallucination about new drugs not adding more survival despite higher prices, makes that very point in another study: " In the absence of significant pricing and total oncology outlay flexibility by payers, our analysis suggests that private sector investment in small oncology segments, and in stratified medicine generally, may not prove economically sustainable, thus endangering the translation of scientific advances into bedside medicines. Beyond increasing reimbursement, decreasing development cycle time and costs, or both, would most directly improve the economic incentives facing developers. By contrast, extending exclusivity periods, or initiating advance market commitments and awarding prizes would likely have less impact and involve greater implementation challenges." (Trusheim, Berndt "Economics of Stratified Medicine" Personalized Medicine (2012) 9(4), 413–427)
So in otherwords, Bach wants lower prices at all costs, even if it kills innovation and people.
Bach is channelling Andrew Wakefield, another lighly published doctor who used the media to advance an agenda that proved toxic to the public health.
Why Is the GOP So Blind on Medicare, Healthcare and Cures
Actually, Curing Disease Is A Pretty Good Way To Save Uncle Sam Money
From our friend and inspiration, Bob Tufts. BT pitched for the Royals around the last time they won the World Series. He was up to see the final out of last night's game and in all the excitement, I forgot to wish him Happy Birthday while we were texting each other. CMPI is celebrating his birthday tonight, not just for his pitching prowess but for his courage and consistent advocacy of medical innovation.
Here's the great article he wrote for the Huffington Post about shutting out cancer and how he did it.
60th and 6th is not a location that you can find on a map of Manhattan, but it is a good place to be.
November 2nd will mark my 60th birthday -- and also mark the sixth anniversary of my return home after undergoing an autologous stem cell transplant to deal with cancer. It is a good time to reflect on the past six plus years and my long journey with this deadly disease.
I was diagnosed with multiple myeloma, a cancer that affects the white blood cells in your bone marrow, on St. Patrick's Day 2009. Nothing can prepare you -- or even your doctor -- to say the dreaded words "you have cancer." It was a shock, especially since I had never missed a day of work from any illness in my life, be it playing major league baseball or working on Wall Street. I considered myself very healthy and did not ever expect to hear these words.
At the time of my diagnosis, my version of myeloma was deemed high risk. If my initial treatment did not work, I might be dead within a year. Fortunately, the pill-based regimen that I received did work extremely well, and by October of 2009 I was ready to have the stem cell transplant to further battle the disease. Five weeks in an isolation room being anemic, having a limited white blood count and suffering from 103 degree fevers and a blistered alimentary system was stressful, but my response to the treatment was excellent. Shortly after coming home I was placed on a maintenance dose of the same medication and I have taken it ever since.
From November of 2009 through today, I have not shown any perceptible sign of the cancer. At this time last year, my oncologist told me that it was time to talk about the "C" word. I nervously asked "do you mean the cancer is back?" He said no, I mean "cure" - you are as close to being cured of an incurable disease as I have seen". I realize that the odds are that I will relapse at some time in the future, but for now I will enjoy the fact that I have told cancer to get lost for at least a few years.
My excellent response to the myeloma treatment made me an outlier, as the median survival rate when I was diagnosed was only one to three years, but science and innovation have changed that. The five year survival rate for myeloma patients is now almost 50 percent, and at some hospitals it is 63 percent. Continuous innovation in the blood cancer field has made remarkable strides in the past decade, and it is poised to do more. If and when I do relapse, other drugs have already been developed in the past few years that can be used to treat me.
Was I now returning home an invalid, unable to contribute to society? Hardly! After a brief period of excess caution to avoid infections, I was able to cook, clean and even assist with my mother-in-law's health care at her nursing home. I was able to be there when our daughter graduated from college. I was able to attend numerous lifecycle events, both happy ones and somber ones. In the past six years I taught approximately 1500 students at three colleges, served as a school advisor, counseled many on career and life choices. I coached hundreds of young baseball players at Major League Baseball Players Alumni clinics. And, I began to attend major medical conventions to deliver the patient's perspective on access and choice in care.
This last item is the most important. If I had lived anywhere other than the United States, systems such as QALY (Quality Adjusted Life Years) are used to evaluate whether treatments should be given to patients based on their expected survival time post-care. In my case, based on some average expected survival rate, I would have been denied the life-saving treatment that I received and would probably have died sometime in 2009.
Perhaps another treatment might have worked, but would you take that chance with your life? Insurance practices such as "fail first" exist, where patient must try the older and less expensive drug and fail to respond to it before being allowed to take the novel therapy. How many patients may have ended up prematurely dead under this scenario where the right drug at the right time is kept away from a person in need? Patients should be proactive and have DNR's, living wills and powers of attorney to make sure their wishes are honored. However, patients should also have a doctor who is ready to fight for their life, with access to as many weapons they deem necessary to battle a lethal disease. That decision should not be a theoretical and impersonal one made by an unseen administrator far removed from your bedside.
These medically harmful attempts to limit access based on an administrator's determination of value need to be debated in the public square. We patients pay the co-pays, insurance premiums, taxes and other fees that fund the entire medical system, but at conference after conference, when discussions on cost and value occur, patients are not represented on the stage. Panelists from on high -- medical administrators, Masters in Public Health and insurance executives -- lecture us about how much we should pay and how our dollars will be divided in the health care system. Bureaucrats want our dollars but do not want our opinions, even though the decisions being made affect the quality of our individual care. The reactions that I receive at conventions when I bring up this point and mention their usage of Orwellian definitions like "choosing wisely," "evidence based" and "unnecessary care" is frosty at best.
I plan to redouble my efforts in 2016 and beyond through "My Life Is Worth It", an online campaign that I co-founded to fight for fellow patients because we want, need and deserve to be at the table when discussions linking cost and value of our care occur. We believe that medical innovation can and will save lives, reduce the cost of health care and stimulate economic growth.
We will continue to push back against "fail first", restrictive insurance formularies, obscene co-pay requirements, time consuming data entry requirements that do nothing other than keep doctors from looking into the eyes of a scared patient with a chronic disease. We will also question the propriety of medical administrators and medical trade groups forming agreements with insurance companies, a blatant conflict of interest against the Hippocratic Oath. We will make sure that the doctor is allowed to practice the art and science of medicine on behalf of the patient and not at the whim of the administrator.
I will question Big Data collection and whether it truly provides value to those who are ill, or does it merely create a system of medicine in which meeting the average or a satisficed level is considered proper care. To borrow a phrase from my baseball days, Big Data may get us in the ballpark, but personal care from a trusted physician gets us to our seat.
We patients are not averages; we have different genomic responses to the initial phases of the disease, its diagnosis, treatment and maintenance protocols. One size fits all care will not advance survival rates or cures. Treating cancer patients based on an average will only yield average results. What is needed is to beat, not merely meet, the norm, to raise the bar and to make the exceptional result today the norm in the future.
I want others to also become outliers, to live longer and better with their chronic illnesses - and to be able to fill their time not merely being alive, but using the time that innovative treatments provide us to be at those lifecycle events - to do the things that make living worthwhile.
I have a lot to be thankful for this November, and celebrating this day with people who reached out to me and my family during our time of crisis is where I want to be today. I lift a glass and say thanks to friends, family and medical professionals whose actions and words helped make today's birthday happen.
This day makes living worthwhile. This is an example of real value that cannot be captured by an app or in an accountant's spreadsheet by those trying to ascertain the value of medical treatments who know the price of everything and the value of nothing.
This party today is being held at the corner 60th and 6th, and I am glad you were able to meet me here. I'm still here, dammit, and I plan to be for a long time.
To all of you who helped, I say thanks again!