Latest Drugwonks' Blog
The bottom line results and approach confirm the wisdom of ignoring anything ICER puts out as self-serving, voodoo economics. See Tom Philipson's excellent discussion of the shoddy short-sightedness of value frameworks here.
I also post a link to yesterday's blog with these updates:
ICER concludes that given that the QALY exceeds what they call the 'norm' of $150K only 1200 out of 32000 patients should be treated. That's rationing. And it has implications for any orphan disease (of which MM is one). That's because in the short term, the use of these new medicines in combination will increase medical costs, not reduce them.
Death and doing nothing is very cost effective.
Further, ICER is setting a trap on combination therapies. That is, it is attempting to send off alarms about how to pay for 2-3 medicines all priced at $150K, etc.
In my previous blog I estimated that ICER would treat only18000 patients, let 34000 people die. ICER's draft report assumes 320000 patients of whom only 1200 would get treatment each year.
As I predicted: ICER didn't even try to set a price for combo therapy:
Indeed, ICER -- unlike previous studies -- refused to set a drug price because it knows that it would be absurdly low to meet it's QALY standard and would be attacked from all sides.
The remarks came at the HELP Committee’s third and final markup of biomedical innovation legislation. The committee voted to pass five bills. The Promise for Antibiotics and Therapeutics for Health Act (S. 185) would create a new pathway for FDA to approve antibiotics for limited populations. The FDA and NIH Workforce Authorities Modernization Act (S. 2700) includes a proposal from Friends of Cancer Research to establish one or more “Intercenter Institutes” within FDA to coordinate activities among centers for drugs, biologics and devices to treat major diseases. It also would give NIH and FDA authority to pay salaries up to the level of the president.
The Promoting Biomedical Research and Public Health for Patients Act (S. 2742) would create five-year terms for NIH institute directors that are renewable at the NIH director's discretion, would remove restrictions on the National Center for Advancing Translational Science funding Phase III studies, and would reduce paperwork for NIH-funded researchers.
The Advancing Precision Medicine Act of 2016 (S. 2713) would authorize NIH to implement a precision medicine initiative. The Advancing NIH Strategic Planning and Representation in Medical Research Act (S. 2745) would require that NIH take steps to increase the numbers of women and ethnic minorities who participate in clinical research.
Alexander said the bills will be combined into a single bill with other biomedical innovation legislation HELP has passed. If agreement on NIH funding is reached and the HELP innovation bills reach the Senate floor, Alexander said several amendments will be offered on topics where the committee hasn’t reached a consensus. These include proposals to create a five-year conditional approval pathway for regenerative medicines and to regulate laboratory-developed tests.
Alexander also said the Senate would vote on an amendment based on the Orphan Product Extensions Now (OPEN) Act, which would grant six months of additional exclusivity to drugs that are repurposed for Orphan conditions.
I wasn't. After all, Amgen had already dealt with ICER's 'methodology' when it recommended that Repatha be sold for $2600 a year and be limited to about 3 percent of patients with statin resistant LDL that could benefit.
The surprise is a function of the fact that the media is buying into to ICER's well-funded – and extremely effective -- attempt to establish itself as the de facto price setting group. It is not a function of the fact that ICER's findings were not pre-ordained.
Amgen believes ICER is "using opaque methods to combine multiple, disparate trials to arrive at different estimates of efficacy, or make assumptions to create unrealistic “worst-case” scenarios. Results produced by independent organizations should be informed by experts, made fully transparent and available, and undergo complete and independent peer-review."
The company is right. ICER defines value as whatever doesn't exceed an arbitrary cap on drug spending as set by PBMs and insurers. But it is clear that ICER is cooking the numbers ala Breaking Bad to get the desired outcome.
Like NICE, the rationing body in the UK, ICER cherry picks data to achieve its desire conclusion. If anyone needs an alternative to incarceration, they should flip through a NICE guidance to see how it picks and chooses what data to accept from companies and what data it uses to say yes or no. It accepts what it wants and rejects what it wants.
The sloppy, even sleazy, approach ICER takes is on full display in it's effort to compare newly approved drugs for multiple myeloma and compare them with the combinations of lenalidomide (Revlimid) plus dexamethasone (Rd) and bortezomib (Velcade) plus dexamethasone (Vd).
Let's set aside that there is no standard treatment for myeloma patients who relapse at ANY stage of their disease. In many cases the combination used is a function of what medicines were used before. Myeloma is incredibly heterogeneous. Yet ICER has no problem making comparisons and assuming every patient will respond the same. The Mayo Clinic's Dr. Rafael Fonseca, on the country's experts in treating MM notes: "The value of these interventions can vary significantly by the presence of this various risk factors. For instance a patient who requires stem cell transplant and is considering maintenance should discuss with the treating physician the various options for treatment based on genetic heterogeneity. Patients with standard genetic factors could very well be treated with lenalidomide versus patients who have high-risk disease where the use of proteasome inhibitors it is highly recommended."
Not only does ICER ignore these important variations, it uses a statistical magic trick – called network meta-analysis -- to turn highly different patients in different clinical trials into carbon copies of each other. ICER never tells anyone how or why it achieves this transformation. It never shares its methods or data and it never submits ANY of it's work to peer review. Instead, a group of 'experts' that also happen to be dues paying members of ICER pass judgment.
At least NICE has patients on their panels, ICER has none. NICE has people who actually use the medicines they are evaluating on their panel, ICER has none. ICER doesn't publish in academic journals: instead it issues it's 'findings' by sending around press releases which are then reported and repeated by medical journals and journalists.
I could go on. The number of scientific offenses that ICER commits could fill a book, a very boring book to be sure. The most important thing to keep in mind, is that for all the statistical mumbo-jumbo, ICER establishes prices and access based upon a GDP+1% cap on the total spending on drugs as a percent of total health spending. That cap, like ICER’s value measure, is arbitrary and set to, as ICER President Steve Pearson has observed, to “set off alarm bells” about drug prices. To that point, ICER will only look at single drugs because it's trying to set the price of each drug so it doesn’t add more than $900 million a year to health spending. Forget about what combination of treatments work best.
So let me save you the time and effort of reading another ICER report and show you how they crank out their pharmaco-economic fairy tales. (Trust me, my rough estimates follow the ICER formula without all the footnotes.)
Pick what you want to spend to extend someone's life from $50K-150K a year (ignoring consensus economics that it's more like $300K)
2. Multiply the list price of a drug by the number of patients that could benefit.
3. Divide that total by the amount you want to spend per QALY (always use $50K even though that number was pulled out of thin air in 1980 to establish the value of dialysis. If you haven't figured out by now, the cost and choice of a QALY cost is subjective. In the case of ICER and Peter Bach's rationing calculator, it assumes insurers and PBM -- and both fund ICER and Bach --will choose the QALY )
4. If your cost per QALY for all patients is above $900 million a year you either reduce the price to meet the cap or restrict access.
So with that in mind let's look at how ICER acts as judge and jury.
1. There are about 80000 people with MM. A recent study estimated that 65 percent of patients will relapse each year. That's 52000.
2. To spend $50k per each life of each of the 52000 would cost $2.6 billion.
3. Which means we need to cut spending by $1.7 billion one of two ways:
Spend only $17000 per patient. (By way of comparison, 20 mg Cialis has annual cost (at list price) of $16800.
Treat only 18000 patients, let 34000 people die.
I won't even discuss combination therapy because ICER won't, even though it's the best way to treat relapsed patients.
You can’t blame the media for not taking a closer look -- or at least the same close look they have applied to pharma -- at how ICER measures value. But that’s because the producers of medical innovation – pharma, biotech, medtech -- have failed to systematically explain the social, economic and medical consequences of the rationing ICER proposes.
So while I agree with Amgen and other companies that ICER (and Peter Bach) is shortchanging value, I can admire how well they have defined the conversation about drug price. ICER has done something pharma, biotech and medtech have the resources to do, but never done. It has effectively and properly defined it's audience as the media, Congress and consumers. It has been proactive and at least gives the appearance of being objective and ‘independent.’
The biotech and pharma industry should support a competitor to ICER, one that -- in concert with patients and providers – uses a long term measure of value that takes into account individual differences in needs and response and outcomes that matter, like productivity, quality of life, physical and emotional independence, time spent with loved ones, caregiver burden.
I hope the biopharma industry ceases fiddling and responds to ICER’s cherry picking of data and who lives and dies.
•Fail first policies in which patients are required to fail on older, inferior treatment before getting the treatment their doctors prescribed;
•Adverse tiering in which most, if not all, medications, including generics, used to treat a condition, such as HIV or Hep C, are placed on the highest cost-sharing tier in which up to 50% of costs are passed on to the patient;
•Clinical pathways in which an insurer pays a practitioner to prescribe a cheaper medicine despite the patient’s needs;
•Prior Authorization in which practitioners can spend up to 20 hours a week on the phone with insurers trying to obtain approval for treatment they’ve prescribed for their patients; and
•Nonmedical switching in which insurers are forcing stable patients to switch to different cheaper medications without even informing the patients’ doctor.
Stacey Worthy, who directs the Alliance policy shop said, “These practices serve to financially exclude patients with a pre-existing condition, create a blatant conflict of interest for the physician, take up valuable physician time trying to obtain approval for the treatments, and in the end, just serve to save company money.”
I’d go a step farther and note that the discrimination is driven by profits. The claim that such restrictions have to apply most drastically to the sickest patients practices to keep costs down is the opposite of the truth.
We know that patients with HIV, Hep C, cancer, pulmonary disease, autoimmune disorders, comprise about 4 percent of everyone with health insurance. Health plans state that drugs for these disease now make up 25 percent of all spending on medicines and about 11 percent total health spending. So that means all the barriers to access described by the AIMED Alliance target 4 percent of patients who make up 11 percent of plan expenditures.
It’s not because the 4 percent are such a burden on our health system. Rather, the growing number of new medicines is a cash cow for pharmacy benefit management companies, insurers and other health institutions. And limiting access is a way to get biopharma companies to pay to play.
Many so-called experts, such as Peter Bach, claim that restricting access to extract discounts is just what we need to reduce drug prices (here he uses hep C drugs as an example):
"Saying no, or even the threat, works to lower prices.. More recently, Express Scripts, a company that manages pharmacy benefits, showed that approval was no guarantee. It was therefore able to play two makers of treatments for hepatitis C off against each other.
Express Scripts, once it showed it could say no, got AbbVie to discount its product. It isn’t saying how much, but Steve Miller, a senior executive, said it had “significantly narrowed the gap between prices charged in the United States and Western Europe.” Sounds like the kind of progress we need."
Don’t believe me?
Read what Credit Suisse reported about the amount of rebate money being pocketed by insurers and PBMs:
“ For 2014, our 20 company universe has shown net US drug sales of $202bn and reported total rebates of $98bn. We conclude that in 2014 US rebates rose 24% against just a 7% increase in net sales, reflecting continued formulary pressures... US rebates rose 24% against just a 7% increase in net sales, reflecting continued formulary pressures.”
Rebates of $98 billion is 32 percent of total US drug sales (for that 20 company group).
That’s a lot of cash being divvied up by Dr. Bach’s noble warriors against drug pricing.
Read Anthem’s lawsuit against Express Scripts, the PBM Bach hails as a pricing savior. Anthem is suing the PBM for not sharing more than $13 billion in rebates over four-year period. The $13 billion is on top of rebates already being given to Anthem.
A good portion of those rebate dollars (I estimate nearly 40 percent) are extracted from the specialty drugs used by the 4 percent of all insured patients (about 11 million). So “by saying no” as Dr. Bach urges PBMs and insurers are able to share – or squabble over -- $40 billion.
That’s about $3600 per person that is going right to PBM, insurers, hospital systems, pharmacy chains.. everyone except the patient.
Peter Bach says that it sounds like the progress we need.
I believe discrimination is not progress, it's illegal and it begs for a legal remedy.
Let’s compare the claims that cancer costs – and drug costs in particular – are unsustainable with the facts:
“One of the fastest growing components of US health care costs is cancer care, the cost of which is now estimated to increase from $125 billion in 2010 to $158 billion in 2020.1 Although cancer care represents a small fraction of overall health care costs, its contribution to health care cost escalation is increasing faster than those of most other areas.”
American Society of Clinical Oncology Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options
“The combination of increasingly unsustainable rises in the costs of cancer care, the accelerating pace of expensive innovations in oncology, and persistent hope for rescue in patients with life-threatening disease require solutions that incorporate and promote value.”
National Comprehensive Cancer Network® (NCCN®) Policy Summit: Value, Access, and Cost of Cancer Care
And now for the facts:
“The increase in people living with cancer and the introduction of new therapies are associated with a rise in cancer care costs. Cancer care costs in the U.S. were estimated to be $124.57 billion in 2010, and are projected to increase to $158 to $173 billion by 2020.
The objective of this analysis was to identify trends in the overall and component costs of cancer care from 2004 to 2014 and to create comparisons to cost trends in the non-cancer population.
We identified the following key dynamics:
1. The percent increase in per-patient cost from 2004 to 2014 for actively treated Medicare fee-for-service (FFS) and commercially insured cancer patients has been similar to the corresponding increase for the respective non-cancer populations.
2. The per-patient cost of chemotherapy drugs is increasing at a much higher rate than other cost components of actively treated cancer patients, driven largely by biologics, but the chemotherapy drug increase has been offset by slower growth in other components.
3. The site of service for chemotherapy infusion has dramatically shifted from lower-cost physician office to higher-cost hospital outpatient settings.
We have important observations on trends in prevalence, cost, and site of service, summarized below:
_Over the entire 2004 to 2014 study period, the average annual increase in cost was essentially the same in the actively treated cancer population and the non-cancer population.
_Cancer prevalence increased from 2004 to 2014 more than the contribution of cancer patients’ cost to the total population spend.
_For patients being actively treated, the portion of spending for cancer-directed pharmaceuticals increased from 2004 to 2014 while the portion of spending for inpatient care declined.
o In particular, the portion of spending for biologic chemotherapies increased from 3% to 9% in the Medicare population and from 2% to 7% in the commercial population.
_The portion of chemotherapy infusions being performed in generally more expensive hospital outpatient settings increased by at least 30%, from 2004 to 2014 with a corresponding reduction in the generally less expensive physician office settings.
_As explained in the body of the report, if the chemotherapy infusion site-of-service distribution in 2014 had been maintained at 2004 levels, the estimated Medicare FFS cost per infused chemotherapy patient in 2014 would have been approximately:
o $51,900 per actively treated Medicare FFS patient instead of the observed $56,100 (7.5% lower)
o $89,900 per commercial patient instead of the $95,400 observed (5.8% lower)
Cost Drivers of Cancer Care: A Retrospective Analysis of Medicare and Commercially Insured Population Claim Data 2004-2014 , Community Cancer Alliance
The ASCO and NCCN value frameworks are based on false assumptions and generated tremendous press and discussion.
My guess is that the Community Cancer Alliance study will be, like many stubborn facts that grate against the anti-pharma narrative, undervalued and ignored. Why let truth get in the way of what we want to believe?
Physicians can take a number of steps to avoid being sued for malpractice, including educating themselves about what contributes to claims, improving lines of communication and building solid patient relationships, according to health law specialists and recent research.
Peter J. Pitts, president of the Center for Medicine in the Public Interest (CMPI) and a former Food and Drug Administration associate commissioner, told Bloomberg BNA the findings are ‘‘not surprising. When a physician is dealing with highly acute patients in a stressful environment, with limited resources and finite knowledge—and with lives literally on the line, mistakes in diagnosis, treatment, and follow-up are inevitable and the opportunity for post-treatment patient education and follow-up is limited,’’ Pitts told Bloomberg BNA March 8 in an e-mail. "Hospitals must be focused on both medical as well as systems solutions that may at first be viewed as ‘cost centers’ but will ultimately result in both better patient outcomes and fewer cases of medical malpractice.’’
Pitts added that regular and open communication is always a best practice when it comes to a mutually respectful physician-patient relationship. ‘‘It is also the best way to prepare a patient for the entire spectrum of potential side-effects and clinical outcomes they may experience over the course of treatment,’’ Pitts told Bloomberg BNA. "Silence and surprise are the enemy of mutual respect and understanding."
The complete article can be found here.
Calculates How Drugs Increase Health Spending By Increasing Life Expectancy
Boston, Mass. April 1, 2016 – The Institute for Clinical and Economic Review (ICER) has posted an updated version of its value based pricing benchmark that takes into account whether new medicines, by allowing people to live longer, contribute to health care spending growing faster than the overall economy.
Currently, ICER establishes a price range within which all patients could be treated with reasonable long-term care value without adding short-term costs to the health care system and increasing health spending more rapidly than growth in GDP.
The new ICER benchmark will include the price of drugs for cancer, HIV, rare childhood diseases and Alzheimer’s and any cost generated by increasing life expectancy.
“We need prices that make sense,” said ICER President Steven Pearson, MD. “Right now, it’s often a black box: we don’t know if we are getting good value with new drugs at these higher prices. A drug even one that saves money in the short term could, by keeping people alive longer, actually wind up costing us more. Our value benchmark currently looks only that whether or not drug spending exceeds an arbitrary cap that maximizes PBM and insurance profits. The new benchmark now measures the value of drugs in terms of how longer life eats into those profit margins.”
“ICER’s new program will make a huge difference by providing what is sorely needed: a source of information about how much rebate money we can pocket before people die,” stated Steve Miller, MD, Chief Medical Officer of Express Scripts, the nation’s largest pharmacy benefits manager. “We look forward to using it to help us improve the ability of patients to get access to new, innovative drugs that keep them alive as little as possible and at a price that maximizes our profits.”
ICER, funded by a $5.2 million grant from the Laura and John Arnold Foundation (LJAF), ICER will produce public reports on new drugs that have the potential to significantly change patient care and health system budgets. As LJAF Vice President Kelli Rhee explained:
“Death is the most cost-effective way of lowering medical costs. If we can find drugs that are good at keep people alive for just a teeny, tiny bit – at least until they pay the next month’s insurance premium – we can make great progress to reining in unsustainable drug spending.”
The new benchmark will be used in developing reports that determine how to ration new drugs. Many of the reports produced will be discussed at the public meetings of ICER’s two core programs, the New England Comparative Effectiveness Public Advisory Council (CEPAC) and the California Technology Assessment Forum (CTAF). ICER tells the media that CEPAC and CTAF are independent, regional bodies of practicing physicians, methodological experts, and leaders in patient advocacy and engagement that provide objective, independent guidance on the application of medical evidence to clinical practice and payer policy decisions in New England and California. But that’s bullshit. They are no more independent of ICER than Crimea is independent of Russia.
In case you didn't know...The press release is an April Fools joke. Just one of many I have seen and received. April Fools’ Day 2016: Round-up of the best (and the worst) joke and prank headlines
Read more: http://metro.co.uk/2016/04/01/april-fools-day-2016-round-up-of-the-best-and-the-worst-5788075/#ixzz44axY1sL6
In two words, no surprises – which for some is better news than for others.
The top of Page 8 will get a lot of attention:
SPECIFIC RECOMMENDATIONS ON CONTENT OF BIOSIMILAR PRODUCT LABELING
FDA recommends that biosimilar product labeling incorporate relevant data and information from the reference product labeling, with appropriate product-specific modifications. The relevant data and information from the reference product labeling that should be incorporated into the biosimilar product labeling will depend on whether the applicant is seeking approval for all conditions of use (e.g., indication(s), dosing regimen(s)) or fewer than all conditions of use of the reference product for the biosimilar product.
In sections of the biosimilar product labeling that are based on the reference product labeling, it is anticipated that the text will be similar. Text based on the reference product labeling need not be identical and should reflect currently available information necessary for the safe and effective use of the biosimilar product. Certain differences between the biosimilar and reference product labeling may be appropriate. For example, biosimilar product labeling conforming to PLR and/or PLLR may differ from reference product labeling because the reference product labeling may not be required to conform to those requirements at the time of licensure of the biosimilar product. In addition, biosimilar product labeling may include information specific to the biosimilar product necessary to inform safe and effective use of the product, which could include differences such as administration, preparation, storage, or safety information that do not otherwise preclude a demonstration of biosimilarity.
And, of course, in order to maintain maximum regulatory, um, flexibility --
FDA acknowledges that there will be variations on the general concepts outlined in this section because the approach to product identification will depend on the specific statements.
(Note – highlights are mine, not FDA’s.)
An update article in Modern Healthcare makes an interesting point, “Federal regulators are likely trying to simplify physicians' understanding of the products' efficacy and safety. By definition, a biosimilar product has no clinically meaningful difference in terms of safety, purity and potency.”
If what practicing physicians understand about biosimilars is anything akin to the knowledge scale of the FDA’s Arthritis Advisory Committee -- as demonstrated during the meeting that considered the biologics license application for a proposed biosimilar to Remicade (infliximab) – then the agency’s attempt at “simplification” may result in some very serious unintended consequences. From the very beginning of the adcomm, it was clear the expert members of the committee didn’t understand what biosimilars really are, nor the pathway the agency uses to review them. Not good.
Can you spell “immunogenicity?”
Per being upfront that the product is a biosimilar, the agency is unambiguous:
FDA recommends inclusion of a statement, on the line immediately beneath the initial U.S. approval date in Highlights, that the product is biosimilar to the reference product. It should read as follows:
[BIOSIMILAR PRODUCT’S PROPRIETARY NAME (biosimilar product’s proper name)] is biosimilar to[ REFERENCE PRODUCT’S PROPRIETARY NAME (reference product’s proper name)] for the indications listed.
Although the FDA notes that the labeling does not need to be identical to information based on the reference product, it’s a pretty safe bet that manufacturers of biologics will likely take issue with competitors using their data for a product that is not exactly the same.
Gentlemen, start your engines.
Consider Utah Attorney General Sean Reyes' op-ed on opioid abuse (A smart way to counter prescription drug deaths). There are a few things that need to be added – and amended.
The vast majority of patients using non-abuse deterrent opioids do so safely and as directed. A subset, approximately four percent, abuse. And government statistics show that 78.5% of those who abuse prescription pain medication did not obtain the drugs from a physician in the first place.
Should non-abuse deterrent opioids ultimately disappear from the marketplace? Absolutely. But removing an entire category of generic products when there are no generic abuse deterrent alternatives not only does eradicate the abuse and addiction problem (since even abuse deterrent opioids can be abused) but punishes the millions of Americans who need opioids to address their chronic pain. Insurance companies are not ready to regularly reimburse for new, abuse deterrent formulations – despite steep discounting by manufacturers. The numbers are staggering -- 240,120,330 non-ADF generic opioids were prescribed in 2015 (nearly a quarter of a billion tablets) versus 5,068,398 branded opioids with ADF properties.
Further, payers often implement barriers to the use of branded, on-label non-opioid medicines, relegating these treatments to second line options. 52% of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment as do 43% of patients diagnosed with fibromyalgia and 42% of patients with diabetic peripheral neuropathy even though there are FDA-approved, non-opioid medicines specifically designed and labeled to treat these conditions.
Payers should step up to the public health plate and do the right thing right now.
Should the FDA, as General Reyes suggests, “… commit to following recommendations made by its advisory committees?” No. That is not the role they play. FDA Advisory Committees advise. It is (and should remain) up to the experts at the FDA to make the final decision. Ultimate responsibility must always reside with the regulator. (The FDA advisory committee that reviewed the controversial opioid Zohydro voted 11-2 that there was no evidence to suggest it had greater abuse or addiction potential than any other opioid.)
Most importantly, a smart public health strategy would be a robust effort to better educate physicians on appropriate prescribing – something the FDA has been calling for regularly. Today the agency announced it will require short-acting opioid pain medications to carry a boxed warning about the serious risks of misuse, abuse, addiction, overdose and death. It’s a good next step.
Should Congress Pass the Cures Act?
Two experts face off on new legislation that aims to speed up the approval process for drugs and medical devices.
IN JULY 2015, the United States House of Representatives approved the 21st Century Cures Act with broad bipartisan support. The legislation, which aims to “save more lives and keep this country the leader in medical innovation,” provides $8.75 billion in funding for the National Institutes of Health and accelerates approval processes for drugs and medical devices. But as the bill heads to the Senate for approval, critics argue that pharmaceutical and biotechnology interest groups will benefit at the expense of patient safety.
Yes. The act will allow the FDA to approve effective drugs and devices faster while maintaining high safety standards, says Peter Pitts, a former FDA associate commissioner and president of the Center for Medicine in the Public Interest.
Where you stand depends on where you sit. If you’re a patient with a life-threatening disease, the FDA is often viewed as a roadblock to innovation. If you’ve suffered a serious side effect of an FDA-approved medicine or device, you may view the process as too swift and cavalier. Both positions fail to take into account a basic truth—there is no such thing as a drug or medical device that is 100% safe.
FDA review is based on a benefit/risk balance. What’s new is that the patient’s voice is now being considered in that calculation. And it’s about time. The FDA has also recognized the urgency of a more comprehensive, strategic program for tracking performance once a product is on the market. A focused, more risk-based approach provides important balance to sophisticated cutting-edge scientific techniques, particularly as we move toward a more aggressive effort to validate biomarkers, that now make it possible to truncate the traditional clinical trial process. Shorter review cycles on the front end are being matched with more rigorous, real-time post-market surveillance.
The draft legislation will allow the FDA to approve a groundbreaking drug if it proves effective after a phase II trial. That will deliver treatments to patients much sooner and eliminate the need for some phase III trials, which take years and account for 90% of the total development costs for drugs that eventually gain FDA approval. The 21st Century Cures Act will also spur new drug development by helping innovators to “fail faster” through earlier and more regular meetings in the review process. Identifying even 5% of eventual failures in phase I instead of phase III will save at least $15 million per drug—allowing drug companies to redirect billions toward promising new treatments.
Victory will result in the FDA bringing new products to market both more quickly and with more information about their safety. Initiatives such as 21st Century Cures will transform the FDA from a perceived roadblock to an innovation enabler.
No, because the act will lower the bar for approval of certain therapeutics, says Ameet Sarpatwari, assistant director of the Program on Regulation, Therapeutics and Law, in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital.
Two sets of provisions are particularly alarming. The first concerns medical devices. The act would prompt the FDA to treat case histories and peer-reviewed studies as valid scientific evidence and would also loosen regulations controlling the safety and effectiveness of alterations to the devices that take place after their initial approval. The creation of a novel pathway would also enable FDA approval of high-risk medical devices on the basis of “clinically significant” surrogate measures, such as their effect on a biomarker, and would also require the agency to complete its review within six months.
Each of these changes could open the door to patient harm. Making approval decisions based on scant data increases the risk of adverse events once a device is widely used, and many surrogate measures have proved to be poor predictors of actual clinical outcomes. Case histories and peer review, meanwhile, are plagued by quality concerns. Additionally, even small changes to medical devices can prove deadly, as several high-profile recent cases can attest. It is better if such changes are reviewed by the FDA, rather than by the company itself or a third party paid by the company.
The second set of provisions involves antimicrobials. To combat the growing threat of multidrug resistance, the act would also authorize the FDA to approve certain antibiotics and antifungals on the basis of preliminary, uncontrolled clinical trials as long as those medications carry a disclaimer that explains their “indicated use in specific populations of patients.” However, evidence suggests that disclaimers on drug labels are inconsistently read, let alone heeded.
These measures collectively represent a fundamentally flawed attempt to promote medical innovation. They would lower the bar for therapeutic approval in several respects, threatening to take us back in time to the patent medicines era in which unsafe and ineffective products flooded the market. The Senate would be wise to start anew in determining what, if any, changes to the regulatory apparatus are necessary as prescription drug and device development expands in the 21st century.