Latest Drugwonks' Blog
If you’re not a regular reader of the Federal register, you might have missed the August 6th notice that the FDA is moving forward with plans to evaluate “distractions” in consumer ads. The experimental study will analyze everything from the placement of text to competition between audio and visual elements, and the use of “major statements.” FDA has opened the proposal for comments until September 5th.
According to the FR, "Data from this study will provide useful information for FDA as it considers whether it is appropriate to develop guidance to help improve how broadcast ads present a prescription drug's risks and benefits."
The FDA will create ads for a fictitious brand to treat high blood pressure to control for participants' prior experience and attitudes. Participants in the study would be men and women age 40 years and older. Everyone will be presented a series of ads—each with different tone, neutrality, and presentation of risk information.
As the terrific Crystal Rice (aka “FDA spokesperson”) told Pharmaceutical Executive Magazine, "We chose high blood pressure as the condition because it is chronic and under-treated, and there are few DTC ads currently running.”
And here’s what I had to say:
"Just like no two people respond the same way to a medication—everyone doesn't respond the same way to advertisements," said Peter Pitts, president of the Center for Medicine in the Public Interest. "The most important thing that DTC advertising does is drive people to their doctor's office to talk about a condition. Whether they glean three, six, or 12 contraindications from a commercial because a child is or is not running through a field of daisies is interesting, but not important."
The complete Pharmaceutical Executive story can be found here.
Okay, I overstated. It is important. Mea culpa. Fair balance and adequate provision serves a useful purpose. (Really!) But, when we consider the social science that’s been done surrounding, for example, the Brief Summary, that “purpose” requires closer examination.
Consider the peer-reviewed study that appeared in Drug Information Journal (Vol. 41, pp 111-127). It found that, when it came to print DTC, “As the number of side effects listed (4, 8, or 12) increased, more consumers recalled no side effects correctly (37%, 45%,, and 53% respectively).” The complete paper can be found here.
(Full disclosure: I am one of the authors of this paper.)
So let’s say, for matter of discussion, that we could devise a method whereby every viewer of every DTC television commercial fully understood everything detailed (you should excuse the expression) in the fair balance/adequate provision.
Is that a good thing or a bad thing?
Well, since better understanding of risk/benefit is, um, better – it should fall into the “good” category, right?
But what if this enhanced understanding results in decreased visits to physicians? Is that a good thing? (According to FDA research, about 6% or all doctors’ appointments are scheduled because a consumer saw a DTC commercial.) What about the undiagnosed conditions uncovered during these appointments. (According to FDA research, in 6% of those DTC-generated office visits, a previously undiagnosed condition was discovered.)
Will the new FDA study capture data that speaks to the increased or decreased likelihood of visiting a physician based on more or less complete recall of risk information?
That’s important context -- particularly since the results of this new study are likely to be highly (shall we say) "media worthy."
Hopefully, the research protocol for this study will be discussed at a future meeting of the agency’s Risk Communications Advisory Committee.
According to reports in the British media, the National Health Service (NHS) has publicly ruled that, “Patients cannot rely on the NHS to save their lives if the cost of doing so is too great.”
What happened to “universal” healthcare? Sounds more like “government” healthcare. Shocking? Not really.
The judgment overrules advice from The National Institute for Clinical Excellence’s (NICE) own citizen's council, which recommended two years ago that it should adopt a "rule of rescue" as an essential mark of a humane society.
According to the citizen’s council, individuals in "desperate and exceptional circumstances" should sometimes receive greater help than can be justified by a "purely utilitarian approach." The council, 27 members of the public chosen to be representative of lay opinion, backed the idea by 21 to 6.
The move was criticized by the British Medical Association, which said doctors had a duty to do their best for patients.
Pretty clear battle lines: cost-based care versus patient-centric care. Government dictate versus physician empowerment.
The NICE report, “Social Value Judgements,” states that treatment may also be refused to elderly patients if the benefits are deemed too low or the risks too high.
Let’s see a political candidate put that on a bumper sticker for “universal” care.
More information on these draconian policies can be found here.
At the same time that British patients are being denied approved care, thousands of terminally ill cancer patients are to be offered the chance to take experimental drugs.
Per a new report in The Guardian, “In cases where the NHS can do nothing more, cancer sufferers will be allocated places in government-backed clinical trials of unlicensed treatments that can prolong some people's lives. A major expansion of the government-funded experimental cancer medicine network will give hundreds, and eventually thousands, of patients the opportunity to join trials of novel therapies which scientists hope to develop into effective new drugs.”
So, on the one hand, no approved drugs for critically ill people – but it’s fine to let them be guinea pigs.
The full Guardian story can be found here.
Is that what they mean by “means testing?”
Is this what our political candidates and their surrogates mean by "universal" care?
SiCKO indeed.
Two issues that are touched on but not really pursued (not surprisingly considering the readership of the journal) are that of (1) the fundamental freedom of free speech and (2) the fact that if drug companies overplay their hands when it comes to off-label promotion there is no shortage of liability lawyers ready to go after them. (Although this article does contain a list of selected healthcare-related fraud cases involving off-label use.)
The complete Nature Biotechnology article can be found here.
Important and timely reading for all of you drugwonks out there as well as for folks like Mr. Waxman.
First let’s talk about transparency.
As John Jenkins (aka, “Dr. Wry”) appropriately pointed out, communications the agency has with sponsors is commercial confidential. That’s the law. The agency’s hands are tied. Period.
Why? Many reasons, but the most important is, well, commercial confidentiality. Trade secrets. Intellectual property. And when it comes to drug development, that’s core business, intelligence other companies would love to see.
But they can’t. And that’s appropriate. It’s at the very heart of a market-based system. The system that has driven unprecedented advances in pharmaceutical development.
The alternative, the so-called “patent-free” idea advocated by Jamie Love and Senator Bernie Sanders (aka, “the Senator from Ben & Jerry’s") was last applied in the former Soviet Union -- and it didn’t work. The Soviet experience was characterized by low levels of monetary compensation and poor innovative performance. The US experience isn’t much better. The federal government paid Robert Goddard (“the father of American rocketry”) $1 million as compensation for his basic liquid rocket patents. A fair price? Not when you consider that during the remaining life of those patents, US expenditures on liquid-propelled rockets amounted to around $10 billion.
Intellectual property rights are the fertile soil that facilitates the tree of pharmaceutical innovation to grow in the first place. To borrow an over-used adjective from the world of global climate change -- we must protect "sustainable" innovation. Jamie Love and Company may very well say, "A world without patents, amen." And they're right, because minus pharmaceutical IPR we'd all better start saying our prayers -- because that's the only way we're going to battle disease and improve the health of our global fraternity. That's a Silent Spring we cannot afford.
The question of honesty, however, is a more difficult issue. “Difficult” because honesty is often in the eyes of the beholder.
If you’re a journalist or pundit, you want as much information as possible. If (post August 11th 2008) the FDA issues a “complete response” letter, you want to see it so you can fully understand and report on the issue. If you’re the sponsor, you don’t want to share it because of both intellectual property considerations – but also because of how the contents of the communication might impact (among other things) how Wall Street views the value of your stock.
Which brings us to the issue of “spin.” Since the sponsor controls what is and is not shared, the sponsor controls what is and is not known. And let’s face it, that can quickly slip/slide into spin. Is not telling the whole truth a lie? It depends on which side of the information divide you reside. At a certain point the sponsor has to make a tough call – is less information better? There’s no hard and fast rule. But one rule is crystal clear – misleading information is just plain wrong.
It’s a fine line.
And speaking of honesty, the news out of Parklawn/White Oak is that 2008 is likely to be one of the slowest years for new drug approvals in the last five years.
Some in Big Pharma (and small pharma and biopharma) blame this on the FDA’s renewed “obsession with safety.” But how can the FDA take action on applications it hasn’t received? The real question is whether or not the FDA has helped or hindered new applications.
Going down this path leads to a discussion of the importance of the Critical Path. And, unfortunately, at present that’s more of a political conversation. Hello Ms. DeLauro. FDA can (indeed must!) be a facilitator – but the main responsibility for 21st century drug development resides with innovator companies.
And hence the importance of intellectual property protection and the need for (yep, you guessed it) commercial confidentiality.
What goes around comes around.
Why? Because, despite clinical evidence that these drugs can actually help, NICE has decided that they’re too expensive. In essence, NICE doesn’t think that these four drugs are value-for-money for the NHS.
Currently, the only available treatment for metastatic renal cell cancer is immunotherapy. This halts the disease’s progress for just four months on average. But if people are unsuitable for immunotherapy, or it doesn’t work, that’s it. There’s no other treatment option.
So doctors urgently need new treatments for this disease. And the four drugs NICE has rejected have shown considerable promise in clinical trials.
These four drugs are part of a new generation of cancer drugs, developed after years of painstaking research. They target key processes within the body that get hijacked when cancer develops.
In fact, several of the trials were stopped early, to allow those people not receiving the new treatment to have it. Other trials showed that some of these drugs could stop the cancer from growing for several months more than immunotherapy alone. That doesn’t seem much, but when you’re trying to beat cancer, those extra months can mean a lot. And NICE’s assessment contains details of several such trials.
NICE agreed that patients tended to live longer when they were given these drugs. But they felt that the evidence wasn’t sufficiently robust. And when they put the data from the trials into their computer models, they found that the drugs cost a lot (£20,000 - £35,000 per patient per year) compared to the benefit they brought patients - too much for them to recommend that the NHS prescribe these drugs.
Doctors don’t have a lot to offer people with advanced kidney cancer. If these drugs can help them - and the clinical trials show that they do - shouldn’t they be made available?
The full statement from Cancer Research UK can be found here.
And according to an article in today’s Daily Mail, “Thousands of kidney cancer patients have been handed an 'early death sentence' under plans to ban life-extending new drugs.”
British kidney specialist Tim Eisen, professor of medical oncology at the Cambridge Research Institute, said, “Patients here are receiving medieval treatment. Together these drugs are the single greatest advance for kidney cancer patients in the last 20 years, yet I and my colleagues face the prospect of being unable to offer treatment that is absolutely standard in every other western European country.”
According to the Daily Mail, “… kidney specialists believe this proposal is a watershed because it requires them to act unethically, offering a lower standard of care than elsewhere in western Europe and the US. Instead doctors will be forced to offer interferon - a medication of such limited use that it is prescribed for just one in ten patients in some cancer units.”
The full Daily Mail story can be found here.
And here’s what our London correspondent, Antoine Clarke, has to say on the matter:
“It means that a rare disease will be neglected by the NHS, in a brutal reversal of the complaint made about poor countries where diseases are untreatable because of a lack of available drugs. Here the research has been done, clinical efficacy demonstrated by the ‘greedy’ drugmakers, but no one will get the medicines because the UK government has decided not enough people die of the disease: ‘only’ 3,600 people out of the 7,000 who are stricken by metastatic renal cell carcinoma. And if you dare buy it out of your own pocket, you will be denied ANY treatment by the NHS, including emergency care, but still have to pay for it in national insurance taxes. Welcome to universal healthcare! America’s tort lawyers will love it!”
And to add to that point consider this additional fact: Nexavar (denied to NHS patients in England and Wales) has been cleared in China.
Welcome to "universal" healthcare.
Consider the headline from this week's BioCentury on the new ESA label, "FDA the enforcer."
Authored by the thoughtful and no-nonsense Steve Usdin, the article calls the agency's action, "a dramatic example of how the FDA is willing to use its new powers ..."
And while this isn't a Clark-Kent-Fortress-of Solitude denouement, it is significant -- and as much for the obvious reasons as for some interesting unintended consequences.
The obvious conclusion is that label changes will happen with greater alacrity. An intended consequence of the FDAAA. On this issue, where you stand depends on where you sit. We think it's a good thing because it does away with delaying tactics that served more of a marketing purpose than a public health one. At the end of the day, intelligent people can disagree -- but it's the FDA's job to make the ultimate call.
A less obvious consequence is enhanced transparency in the label discussion process. Usdin writes:
"FDA has been unusually transparent about its interactions with Amgen over ESA labeling in the cancer setting. The agency has released correspondence with the company that describes labeling negotiations, detailed points of disagreement and explained its position in interviews with BioCentury and other news media, and posted redlined copies of the label that highlight changes."
We think that enhanced transparency is a good thing too.
Further, according to Usdin, "The disclosures suggest it would have taken longer to negotiate the changes, and the final language would have been different, in the absence of the new authorities."
Faster? Yes. Different? Maybe. But we now know who wanted what and why. And that's important.
Consider Amgen's statement:
"Amgen has worked closely with the FDA to develop the new label and has no plans to appeal. Although we may have disagreed on specific points, we are pleased that the final label permits physician discretion and recognizes the known benefit:risk profiles of ESAs at this time."
Well, so much for FDA being in the pocket of those it regulates.
We'll give Richard Pazdur the last word (because that's the way he likes it):
"This is a journey and we have not completed it."
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.
