Latest Drugwonks' Blog
From the pages of Drug Industry Daily:
New FDA Drug Approval Pathway Aims to Promote, Ease Enrichment Trials
The FDA is considering a new drug approval pathway intended to boost development of treatments targeting small subgroups of patients with serious or life-threatening conditions.
The pathway would establish a new, speedier process for studying a new drug or biological product in a smaller subpopulation of patients with more serious manifestations of a disease.
Labels for drugs approved under the new paradigm would make clear the drug is narrowly indicated for use in limited, well-defined subpopulations in which the drug's benefits have been shown to outweigh the risks, the agency said in a Federal Register notice.
The FDA plans to hold a public hearing on the potential new approval pathway on Feb. 4 and 5.
The agency is allowed to "exercise its scientific judgment" under existing regulations to determine the level of data a sponsor must provide in support of a particular candidate. Such flexibility has spurred the advance of a wide range of orphan drugs for rare diseases.
But traditional drug development programs typically require very large study populations, which put subpopulations of patients with more severe conditions at a disadvantage in the clinical setting - a situation that often results in less timely availability of new drugs for those patients.
The new approval pathway "could involve smaller and more rapid clinical trials than would occur if the drug were studied in a broader group of patients with a wide range of clinical manifestations," the FDA said.
The pathway proposal comes on the heels of new draft agency guidance on strategies for developing enrichment trials, which prospectively apply a patient characteristic to select a subpopulation more likely to benefit from a drug.
"The two announcements coming together signal to the industry that the blockbuster model is slowly being replaced by the personalized medicine model," Peter Pitts, president of the Center for Medicine in the Public Interest, said.
The message to the investment community is that drug failures are often due to trial design difficulties and not just heavy-handed regulation, he added. The proposed approval pathway is not likely to allow for less-robust evidence, just a different kind of evidence, Pitts cautioned.
Public Hearing Questions:
The meeting at the FDA's White Oak Campus will address such issues as:
The pathway's necessity considering the existence of other expedited approval pathways;
The conditions and patient subpopulations most likely to benefit from the pathway;
The degree to which regulators should monitor drugs approved under the pathway; and
Whether the pathway should be used to help reduce antibiotic-resistant bacteria by limiting the drugs' use to those patients in whom use is "appropriate and necessary."
Comments are due to docket no. FDA-2012-N-1248 by March 1. View the Federal Register notice at
www.fdanews.com/ext/files/01-14-13 DrugApprovalPathwayMeetingNotice.pdf.
“Human action can be modified to some extent, but human nature cannot be changed.” Those are the words of Abraham Lincoln (16th President of the United States and Academy Award nominee). And they pretty well sum up a major issue in American healthcare – adherence/compliance.
I’ve just returned from the speaker’s podium at the Optimizing Pharmaceutical Patient Adherence conference. There’s a lot to be done. There are a lot of good ideas. There seems to be a lot of commitment. The better angels of our nature were on display.
Now it’s time for action.
Zig Ziggler once said, “If what you’re doing isn’t working, try something else. If what you’re doing is working, try anything else.” While there are certainly success stories and validated methodologies in the battle for better adherence/compliance, we’re losing the war. It’s time to reconsider what we’re doing.
And the first thing to admit is that we can’t relegate the conversation to healthcare policy. While the conversations are fascinating – another white paper, another committee, another conference – isn’t going to move the needle. We need to act.
As I see it, there are six issues we are trying to impact – and they are linked:
1. Sub-optimal patient outcomes (the Big Kahuna).
2. Sub-optimal physician pay-for-performance metrics. (More important today than ever and back at the top of strategies to control costs. Alas – one of the unintended consequences of pay-for-performance is that some physicians will try to game the system by not seeing those patients who they see at high risk for non adherence/compliance,)
3. Lower healthcare costs for payers. Not surprisingly, all of the big private payers are in the adherence/compliance game with both feet.
4. Sub-optimal profits for pharmaceutical companies. (The sale doesn’t end once the script is written.)
5. Impact on safe-use. The way to make drugs “safer” is to ensure they are used appropriately. Safe use begins with adherence/compliance. (Hear that FDA?)
6. Lower healthcare costs for society. (You might have heard of this issue – it’s been in the news a lot.)
Alas, there are no magic bullets in the fight to improve adherence/compliance. News articles feature talking pillboxes that offer bells and whistles, rings, buzzes, and flashes, and that’s all to the good – but they only combat forgetfulness (purposeful or otherwise). It’s a part of the solution – but, just as in the battle against counterfeit medicines, it’s only a piece of the puzzle
Some think that (as with REMS), the FDA should insist that new drugs have adherence/compliance plans that can be monitored and improved through iterative learning. Should sales reps (or, better yet, MSLs) “detail adherence/compliance programs and share validated tools for adherence/compliance “triage?” The only thing that’s currently on the table is that the FDA has promised to make MedGuides more user-friendly. (We can do better.)
Others talk about behavior modification through gamification – and that too is a useful pathway. We talk about carrots – but what about sticks to address bad patient behavior (particularly sticks of the financial variety)?
All of these are important. But talking pillboxes and better MedGuides are only making existing tools better. And trying to “regulate” adherence/compliance is a slippery slope indeed. To really make a difference, to change the game, what we really need are solutions that impact social conditioning and address patient responsibility – and that means using innovative platforms such as social media and, specifically, apps.
Not apps that are medical devices (although those play an important role in 21st century healthcare), but apps that remind, cajole, educate, praise, incentivize, and assist patients in their quest for better health. Apps are at the nexus of sage use, treatment outcomes, and patient satisfaction. And it’s not science fiction.
At present, there are some 17,828 healthcare and fitness apps and 14,558 that can be deemed “medical.” While some are better than others, these numbers tell us one thing – this is not a fad or a trend. It is reality.
And as Philip K. Dick wrote, “Reality is that which, when you stop believing in it, doesn’t go away.”
Will our socio-economic “technology gap” lead to a more pronounced “adherence/compliance gap?” It’s an important question. That’s why it’s crucial we remember there is no one-size-fits all solution. But that’s mustn’t mean we disregard the reality of the growth and pervasiveness of apps, mobile apps. Let’s face it, when it comes to mobile phones, any gap is rather narrow.
Apps for adherence/compliance are “safe use” apps. Apps that can be “prescribed” by physicians to their patients are the wave of the present. Adherence/compliance “app-ens” and patients, physicians, payers, pharmaceutical companies – and society benefit.As Walter O’Malley (the man who moved the Dodgers from Brooklyn to Los Angeles) famously opined, “The future is just one damn thing after another.”
FDA will hold a public hearing on Feb. 4-5 to obtain input on creating a new approval pathway for therapeutics for limited, well-defined subpopulations of patients with serious or life-threatening conditions, including infections caused by antibiotic-resistant bacteria. According to the agency, such a pathway could allow companies to evaluate safety and efficacy in subpopulations of patients with more serious manifestations of a condition. The result, said FDA, could be smaller, more rapid clinical trials than studies in a broader group of patients with a wide range of clinical manifestations. The agency said a narrow indication of therapeutics approved via such a pathway could be expanded based on additional data demonstrating efficacy and safety in a broader population.
FDA is seeking input on the need for and feasibility of such a pathway, as well as its potential advantages and disadvantages. The agency is asking stakeholders to discuss which diseases or conditions would benefit from such an approval pathway, as well as whether the pathway would increase the number of therapeutic options in the context of the agency's existing expedited processes, including accelerated approval and the Fast Track program. FDA also is seeking input on how the agency could monitor use of drugs approved under the pathway. Comments are due March 1.
Good for them and good for those who could otherwise be exposed to someone with influenza. Hospitals, nursing homes, and physician offices are happy hunting grounds for viruses since the odds of infecting -- and killing -- an immunocompromised patient are much higher in those settings. I agree with Art Caplan:
"Medical ethicist Art Caplan says health care workers' ethical obligation to protect patients trumps their individual rights.
"If you don't want to do it, you shouldn't work in that environment," said Caplan, medical ethics chief at New York University's Langone Medical Center. "Patients should demand that their health care provider gets flu shots — and they should ask them."
For some people, flu causes only mild symptoms. But it can also lead to pneumonia, and there are thousands of hospitalizations and deaths each year. The number of deaths has varied in recent decades from about 3,000 to 49,000.
A survey by CDC researchers found that in 2011, more than 400 U.S. hospitals required flu vaccinations for their employees and 29 hospitals fired unvaccinated employees."
Meanwhile Shannon Brownlee of the New America Foundation, the reputed health care expert who never saw a patient or worked in the industry, is a cheerleader for this selfishness. If you don't count Bill Maher.. (I wonder if you need a flu shot to party at the Playboy Mansion?)
To be sure, there are those on the right who also regard vaccination as somehow another form of government control..I have laid into them as well.
Finally, the vaccination shortfall among health workers reflects the transformation of the scientific method into a propaganda tool for organizing against and calling for the regulation (and removal) of every so-called "danger." Data dredging to establish statistical associations between what is regarded as evil has proliferated and turned most medical journals into stringers for bloggers, activitsts, the media and politicians of all stripes. With regard to the flu vaccine, we are still paying for the assault on vaccine safety (led by the media) of years past. Some vaccines are less potent in part because of fears. We have blunted the effectiveness of the HPV vaccine and have spawned a generation of 20-somethings with the highest rate of oral, throat, anus and mouth cancers ever.
If we use science to foreclose all things defined as danger, we will also increase exposure to unforseen events and we degrade our ability to respond to them.
The conversion to electronic health records has failed so far to produce the hoped-for savings in health care costs and has had mixed results, at best, in improving efficiency and patient care, according to a new analysis by the influential RAND Corporation.
Optimistic predictions by RAND in 2005 helped drive explosive growth in the electronic records industry and encouraged the federal government to give billions of dollars in financial incentives to hospitals and doctors that put the systems in place.
Read the full piece here.
GOP lawmakers are praising the FDA’s 24-page draft guidance on abuse-deterrent, opioid painkillers. House Energy and Commerce Committee Chair Fred Upton (R-MI) and Sen. Tom Coburn (R-OK) issued a joint statement, commending the agency for meeting the draft-guidance deadline established by the Food and Drug Administration Safety and Innovation Act of 2012.
National Drug Control Policy Director Gil Kerlikowske "called the action a vital piece of the Obama administration's effort to curb" the nation's "prescription drug abuse epidemic." However, not everyone applauded the document's release. Former Republican Rep. Mary Bono Mack of California, who co-chaired the "Congressional Caucus on Prescription Drug Abuse before she was defeated in November," dismissed the FDA's nonbinding recommendations as "lip service," and called for "more definitive action."
Getting praised for hitting a Congressional deadline is faint praise. But the FDA’s efforts are a lot more than window dressing. Sorry, Mary.
The next issue to watch is how FDA deals with generic opiods – and whether Congress and the courts intervene.
Stay tuned.
Rather, I would reluctantly call attention to the media's portrayal and premature release of a study claiming a statistical association between soft drinks and depression. I could only find an abstract and here it is:
Abstract Title: Sweetened beverages, coffee and tea in relation to depression among older US adults
Press Release Title: Hold the Diet Soda? Sweetened Drinks Linked to Depression, Coffee May Lower Risk
Objective: To prospectively evaluate consumptions of sweetened beverages, coffee and tea in relation to
depression among older US adults.
Author(s): Honglei Chen, MD, PhD, Xuguang Guo, Yikyung Park, Neal D. Freedman, Rashmi Shinha,
Albert Hollenbeck and Aaron Blair
Background: Sweetened beverages, coffee and tea are commonly consumed worldwide and have important
physical and mental health consequences.We prospectively evaluated consumptions of these beverages, in relation to depression
among 263,925 older US adults. Beverage consumptions were assessed in 1995-1996, and 11,311 depression
diagnoses since 2000 were self-reported in 2004-2006. Odds ratios (OR) and 95% confidence intervals (CI)
were derived from multivariate logistic regressions.
Results: Drinking sweetened beverages was associated with higher depression risk, whereas coffee drinking
was weakly related to lower risk. The OR and 95% CI comparing ≥4 cans/cups per day with none were 1.30
(1.17–1.44) for soft drinks, 1.38 (1.15-1.65) for fruit punches and 0.91 (0.84-0.98) for coffee (all P for trend <
0.0001). Further analysis seemed to suggest stronger associations with diet drinks than with regular. The ORs
between extreme categories were 1.31 (1.16-1.47) for diet versus 1.22 (1.03-1.45) for regular soft drinks, 1.51
(1.18-1.92) for diet versus 1.08 (0.79-1.46) for regular fruit punches and 1.25 (1.10-1.41) for diet versus 0.94
(0.83-1.08) for regular iced tea. Consistently, constituent-based analyses showed higher depression risk with
aspartame intake [ORs between extreme quintiles: 1.36 (1.29-1.44)], and lower risk with caffeine intake
[corresponding OR 0.83 (0.78-0.89)].
Conclusions: This large prospective study suggests that frequent consumption of diet sweetened beverages
may increase depression risk among older adults, whereas coffee consumption may lower the risk.
So let's set aside the methodological problems (no regular follow up of consumption, depression or other health conditions associated with depression such as diabetes or heart disease, surgical procedures associated with depression) as well as the fact there is no clear definition of what kind of depression (major depressive, mild or bipolar). The geniuses behind this study claim the odds ratio for a self report of depression ranged from 1.31 for soda drinkers (whether diet or sugar) to .083 for people drinking coffee.
The problem is two fold:
1. The lifetime odds ratio for people ages 45-65 being diagnosed with major depressive disorder at any time in life is 2.0 and for age 65 and over it is 1.0. So that means that risk for depression for older people drinking soda actually was less than the general population.
2. The hazard ratio for age of onset declines at age 45, spike at age 50, declines again until age 65. So it's likely, absent controlling for other conditions and demographics that the 'depression-soft drink' association is only mirroring the hazard rate.
Finally, there are several other conditions and demographic elements that are several times more likely to be associated with major depression.
You can get more information about the real risk of major depression and it's possible risk factors here:
That is unless you have already made up your mind. For those of you that have you might want to know that the same lead author found that smoking was associated with a decline in risk for Parkinson's..
What is the British Medical Journal smoking?
In a new editorial, “Patients are urged to boycott trials that do not guarantee publication," the BMJ (along with other organizations) calls on patients to boycott clinical trials that promise, “to publish the results in full.
Tracey Brown, director of Sense About Science, an ally in this effort, is quoted in this effort saying, “Everybody agrees that clinical trials should be registered and that we should at the very least have clinical reports on what was found.”
Really? “Everybody” agrees? While there is general agreement – and strict government regulations -- on the registering of trials, the idea of publication of every trial fielded is, well kind of loony.
Should pharmaceutical companies guarantee that regulatory bodies such as the FDA and the MHRA see all important data before new products (or additional indications) are approved? Of course. And, incidentally, that’s the way it works. Any company that withholds important clinical information pays a severe price – and not just financially.
According to Iain Chalmers, of the James Lind Alliance, Paul Glasziou, professor of evidence based medicine at Bond University, Queensland, and Fiona Godlee, editor in chief of the BMJ, the withholding of trial results is important to people in trials because, “participants in clinical trials assume that they are contributing to the advancement of medical knowledge; non-publication of study results negates this reasonable assumption and betrays those who have volunteered.”
Balderdash. Note to Mr. Chalmers, Mr. Galsziou, and Ms. Godlee – patients in clinical trials do indeed provide a brave and noble service to the advancement of science whether or not any given trial results are published.
And what does this myopic triad have to say about clinical trials as intellectual property? Not surprisingly, they are silent.
Third party funders of trials certainly have the right, as part of their grant terms, demand publication. But privately funded trials also have the right to maintain the confidentiality of their findings – until they chose to submit them for regulatory review.
By furthering the anti-IP agenda of the Usual Suspects, the BMJ does a disservice to those they are trying to protect -- patients. Full publication of every trial fielded will not result in safer, better designed trials -- only in fewer trials. Cui bono BMJ?
Who paid for prescription drugs in 2011?
According to Health Affairs, data for 2011 (the most recent year available) shows that the two primary CMS programs -- Medicare and Medicaid -- paid for 32% of total retail drug spending. The private health-insurance share, which was 46.5% in 2011, peaked in 2001 at 51% and has been declining ever since.
For the second year, spending on outpatient prescription drugs grew more slowly than overall national health expenditures. In 2011, prescription drug spending grew by 2.9%
Healthcare reform reduced Medicaid spending. Medicaid spending declined by 3.0% in 2011, following a 1.4% drop in 2010.
And consumers paid even less. In 2011, consumers’ out-of-pocket expenses -- cash-pay prescriptions plus copayments and coinsurance -- shrank to an historical low 17% of total U.S. retail drug expenditures.
The complete Health Affairs report can be found here.
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.
