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According to a report in today’s Guardian, the ban on drugs that can give kidney cancer patients many months of extra life is to be lifted. At least two, and possibly all four, of the medicines that had previously been deemed too expensive to prescribe will be approved by the National Institute for Health and Clinical Excellence (NICE) early next year.
What caused the the reversal? Why evidence, of course.
"A spokeswoman for NICE said the organization was looking again at all the drugs because there was more evidence submitted during a couple of periods of the appraisal process by manufacturers, which needs to be discussed by the [appraisal] committee. We will publish a next draft within four weeks of the committee's meeting in January and issue final guidance in March 2009.”
Couldn't have been anything else, right? Well ...
"The move follows British Health Secretary Alan Johnson's decision this month to overhaul the way new medicines are assessed for terminally ill patients. Denying cancer patients access to drugs that are widely available abroad has become a major political issue."
For more on this issue, see here.
And for the complete Guardian article, see here.
Perhaps HHS Secretary/Healthcare Czar-Designate Daschle should give the Honorable Mr. Johnson a call. And maybe he should conference-in Senator Baucus.
Per the renewed interest in ALLHAT -- and the pros and cons of large scale, government-funded comparative effectiveness trials -- some further comment from Michael Weber, MD -- one of the original ALLHAT investigators (and Chairman of the Center for Medicine in the Public Interest):
Using ALLHAT as an example of an “evidence gap” could be misleading, for the issue is not the information produced by ALLHAT, but rather how it’s interpreted and used.
Most experts, myself included, have concluded that diuretics are highly useful drugs in treating hypertension, and may even be underutilized. But there is no convincing evidence that they are superior to other drug classes.
Admittedly, diuretics are cheap to acquire, though not necessarily cheap to use. Because they cause unwanted changes in such factors as potassium, glucose (which can lead to diabetes) and uric acid ( which can lead to gout), the additional costs of extra laboratory tests, follow-up doctor visits and corrective therapies must be reckoned in.
In fact, the British National Health Service, which is guided in drug selections by its highly cost-sensitive National Institute of Clinical Excellence, favors amlodipine (one of the diuretic’s competitors in ALLHAT) as the usual starting therapy for hypertension. This recommendation is based on the ASCOT study that found that a beta-blocker/diuretic combination (a favored treatment in ALLHAT) was significantly less effective than a combination of newer drugs in reducing fatal and non-fatal cardiovascular events and strokes.
Another powerful study, ACCOMPLISH, was recently presented at the scientific sessions of the
So the claim of an evidence gap is not based on a disregard of evidence, but in fact demonstrates that the opposite is true. Clinicians apparently are aware of the full spectrum of evidence, not just selected portions promoted by a government agency. From the perspective of patients with hypertension, this surely is good news.
(For more on ALLHAT, see here.)
The “internacional” part consisted of myself, Michael Drummond, Professor of Health Economics (University of York), Professor Jacques Lelorier, Chief of the Pharmaco-economics and Pharmaco-epidemiology research unit at the University of Montreal, and Kalipso Chalkidou, Acting Director of Policy Consulting at NICE.
The seminar was designed to debate and discuss Mexico’s new pharmaco-economic guidelines for their national formulary. And there was as much debate as discussion. (The audience was comprised of about 100 members of various Mexican government health authorities – and they were not passive observers.) The opening remarks by Stephano Bertozzi (Instituto Nacional de Salud Publica) set the tone for the event, “We need to spend more and spend more wisely.”
Michael Drummond’s presentation was a primer on the various types of evidence used in healthcare technology assessments. Nothing new – but a valuable view into the soul of HTA. Dr. Drummond’s take-away message was that decisions made via HTA are economic decisions – not necessarily medical ones. He also pointed out that using RCTs as the mainstay of comparative effectiveness measures was a flawed proposition and that other evidence – such as observational studies and real-time outcomes data needed to become part of the broader HTA equation.
I was up next, and the gist of my talk was that decisions should be made on patient-centric rather than cost-based platforms – and that reimbursement choices based on short-term budgetary considerations can have expensive (for the government) and dire (for the patient) consequences. My presentation can be found here.
Third on the agenda was Professor Jacques Lelorier who gave a very provocative presentation on the gaming of the comparator issue in general and by Canadian authorities (CDR) in particular – which does not tell the innovator company what comparator it has chosen and then, once a decision has been made, won’t share the data used in the process. He made the point (echoed by others during the course of the event) that when a particular HTA review finds a product to be outside of the selected cost-effectiveness parameters, “the answer is no,” but when the parameters fall within the selected criteria, “the answer is maybe.”
Kalipso Chalkidou gave an overview of NICE – making a point of the fact that NICE is not a reimbursement agency and does not deny access to pharmaceuticals. She also discussed the pending policy (in the UK) of providing physicians with financial “incentives” if they move patients from on-patent medicines to generic alternatives “Incentive” -- such a nice word when a government uses it. Can you imagine what it would be called if this same technique was used by an innovator company? (Hint – “bribery.”) Dr. Chalkidou also noted this policy is “pending” because it is being challenged in court. She also pointed out (vis-à-vis statins) that if there was “any proof” that an on-patent product was “better” than a generic that NICE would be glad to reconsider its current position on the matter. I will shortly send her a link to the BMJ-published THIN study that shows why switching patients from on-patent atorvastatin (Lipitor) to off-patent simvastatin (generic Zocor) has proven to be very expensive to the British healthcare system because of its disastrous and deleterious impact on patient health. (For more on the THIN study, see here.)
Day Two of the seminar was comprised of Mexican health officials and academics presenting their views on pharmaco-economics and HTA. Some worthwhile and representative remarks:
“Developing guidelines is one thing -- making disastrous implementation mistakes is something else. We must have confidence in the people doing our HTA reviews and understand the relative strengths and weaknesses of the data. We must have clarity about appeal guidelines. A good economic analysis is not a faultless crystal ball. HTA has threats as well as opportunities.” (Atanacio Valencia, Institudo Nacional de Salud Publica)
“HTA isn’t a decision – it is the evidence to assist in making a decision.” (Maria Cristina Gutierrez Delgado, Secretaria de Salud). Her presentation was on a Mexican HTA analysis of the HPV vaccine – an analysis that showed the vaccine not to be cost-efficient. The Health Minister, however, decided to go against that recommendation.
Stephano Bertozzi spoke about the need to create a formalized training program for those who prepare HTA studies as well as for those who will make the final reimbursement decisions.
Octavio Amancio Chassin (Consejo de Salubridad General), made the excellent point that HTA must go “beyond the QALY,” taking into careful consideration a variety of factors such as the financial impact associated with caregivers.
Being able to participate in this event and to view the Mexican public health community discuss and debate how to set up an HTA authority convinces me of five things:
1. HTA can be a valuable tool when the right tools are used the right way;
2. HTA must be a combined and collegial effort of government officials, trained academics, physicians and pharmaceutical companies;
3. A variety of evidence must be considered – from RCTS to observational studies to outcomes data;
4. HTA must be as much a patient-centric proposition as a cost-effectiveness mechanism;
5. All aspects of HTA – from the design to the decision to the appeals process must be open and transparent
As we in the United States begin to think seriously about HTA we absolutely must remember that it’s more than just “comparative effectiveness.” And a good way to start having a serious conversation about the issue would be to convene experts and discuss the right way to move forward.
I respectfully suggest to Senator Baucus and Senator Conrad, before they offer legislation setting up an American comparative effectiveness body (within AHRQ or anywhere else), that they look at the process being used by our NAFTA neighbors to the South and carefully consider the warning of Professor Atanacio Valencia, “Don’t make the remedy worse than the disease.”
CMPI's chairman Michael Weber is quoted:
“There was a feeling there was a political and economic agenda as much as a scientific agenda,” said Dr. Michael Weber, a professor of medicine at the Health Science Center at Brooklyn, part of the State University of New York, who had been an investigator in the study but afterward became one of its leading critics. “They pushed beyond what the data allowed them to say.”
Critics said the rules of the trial had favored the diuretics. If the first drug did not adequately lower blood pressure — as happened in more than 60 percent of cases — a second drug could be added. But that second drug was usually a type that worked better with diuretics than with ACE inhibitors.FDA's Bob Temple says: “This is the largest and best attempt to compare outcomes we are ever going to see,” he said. “And people are extremely doubtful about whether it has shown anything at all.”
So who is in favor of this big trials?
Those who want the government to dictate to doctors what to prescribe based on cost-driven clinical trial designs or think they will spit out precise answers that health plans can use to save money. But in fact such trials themselves have a political edge and often lead by people who themselves have a bias: Which is why Curt Furberg, the man who played fast and loose with the data to claim calcium channel blockers cause cancer, was forced to resign. Actually not the only reason. The other reason: the design of ALLHAT exposed African Americans to an excess risk of stroke and stroke related death. President-Elect Obama and his health advisers should bear that in mind in considering Furberg for any position.
So what's the verdict on comparative effectiveness research? Clinical trials of the size, scope and design of ALLHAT are inconclusive and often outdated, if not politically motivated. So what's the alternative that everyone is seeking to spend billionns on?
"Dr. Clancy (Carolyn Clancy director of the federal Agency for Healthcare Research and Quality) said that her agency was now mainly using insurance records to judge how treatments perform. While clinical trials are the gold standard, she said, they are costly and time-consuming.
And, she added, “You might be answering a question that by the time you are done, no longer feels quite as relevant.”And that's going to save the US health system billions?
Research on how to achieve the best outcomes for patients is possible. But neither the ALLHAT approach or the review of insurance records is the way to do it.
As in "Chicken Little."
I share this because, having just landed in Mexico City for a conference on HTA and pharmacoeconomics, I can attest to the fact that the sky is not falling – notwithstanding a story in today’s Washington Post that the FDA is teetering on the brink.
Consider the opening paragraph:
“Shaken by a series of alarming failures, the FDA desperately needs an infusion of strong leadership, money, technology and personnel -- and perhaps a major restructuring, say former officials, members of Congress, watchdog groups and various government reports.”
First of all, the agency already has some very high caliber leadership – but a new Commissioner with vision, guts and communication skills will absolutely make things better. The FDA is a very hierarchical agency. And it’s very true that more money, personnel and technology are must haves. Particularly technology.
But folks, as Pollyanna-ish as it may sound – the agency that parlor game pundits, some of our elected officials and so-called “watchdog groups” are bemoaning as broken – is actually working pretty well considering withering media attacks, internal score-settling and general hand-wringing by people who mostly have no idea what they’re talking about.
And some who do and should know better.
I am surprised by the comments of my former colleague Bill Hubbard who is quoted in the Post as saying, "FDA is close to being at a tipping point -- the agency is hanging on by its fingertips in protecting us."
If that’s true today, then it must have been true when Bill and I were at Parklawn together. And it wasn’t true then. Bill wants the best for the agency – but tacking to the political winds is bad strategy.
"Everywhere you go, you hear the same chorus: The agency's in trouble," said David A. Kessler, who served as FDA commissioner under Presidents George H.W. Bush and Bill Clinton. "There's a general perception the agency is suffering mightily."
It’s important to read what Dr. Kessler said – that there’s a general “perception” – that’s a lot different from it being true. But minus a smart and robust communications strategy – perception becomes reality. And the FDA has been minus a smart and robust communications strategy for too long.
And then there are those with personal agendas.
"I'm afraid we're going to see more horrible things happen if we don't get our act together on this," said David Ross, who was a drug reviewer at the agency for 10 years.
Funny the article should quote David Ross – who has a chip on his shoulder the size of Gibralter. It’s kind of like asking Hillary Clinton to write a job recommendation for Monica Lewinsky. It’s also poor reporting that Ross’ conflicts weren’t noted.
Sloppy journalism and bad editing.
And then there are those who point out how well the FDA was run when they were running it:
"The agency needs to get back to using science as the basis for its decision-making," said Jane E. Henney, who ran the FDA under Clinton from 1998 to 2001.
Let’s face it -- Jane will not go down in history as one of the great FDA Commissioners. And shame on her for saying the agency isn’t using science, first, last and always as it’s decision-making compass.
The article makes one excellent point that needs to be repeated and repeated and repeated, “While the agency has received some additional money and personnel to help implement new drug safety powers, many say it is overdue for a doubling of its budget.”
That’s change we can believe in – lots of change.
And, according to Mark McClellan – already considered by many to be one of the FDA’s Hall of Fame Commissioners -- "There's broad bipartisan recognition from consumer groups and from industry that the FDA needs more resources. The most important thing is overall effective leadership that leads in a way that establishes public trust."
Amen.
And Happy Thanksgiving.
Last March (March 4th to be exact) drugwonks.com commented on the hypocritical disconnect between what medical journals were writing about medical journalism conflict-of-interest and what they were practicing (“New Realism Redefined”) -- “There seems to be a lot of "do as I say not as I do" going on these days.”
A few months later (August 25th), Steve Usdin of BioCentury weighted in on the same topic. His article, “Sacred vs. Profane,” began as follows:
“Medical journal editorials routinely attack the pharmaceutical industry, alleging drug companies corrupt the practice of medicine through inappropriate and overly aggressive marketing, while also criticizing doctors for allowing themselves to be influenced. The journal publishers themselves, however, play a key role in encouraging the behaviors their editors criticize via advertising, sponsored subscriptions and the promotion of reprints of company-sponsored clinical trials.”
(It should also be noted that both JAMA and NEJM declined Usdin’s requests for interviews.)
So it comes as somewhat of a surprise (Really? No.) that in the current edition of the British Medical Journal (19 November 2008, doi:10.1136/bmj.a2535), much of the same ground is covered – but minus any mention of the sins of medical journals!
Maybe not.
Did Joe Biederman do anything unethical or wrong by asking Johnson and Johnson to support a research center to develop gene and imaging based diagnostics to more accurately screen for child and adolescent bipolar disorder and then use risperidone (and other drugs) to conduct open label and randomized clinical trials to establish if treatment based on new screening criteria produced better results?
Yes. Biederman should have been more transparent or more promotional about it. Because in this day and age if you don't let your enemies know what you are doing by definition you are hiding something. And if you are hiding something you are by definition conspiring to poison people (particularly children) with drugs that are "powerful" but somehow also "ineffective" and dangerous.
Should J and J not have decided to spend $6 million promoting awareness of bipolar conditions in kids, support CME with unrestricted grants and seek ideas on the appropriate way to design studies for pediatric labeling?
It should have been more open, more willing to give up control and let the science and consensus go where it might instead of letting marketing people try to micromanage.
It's the secrecy stupid. You have nothing to be afraid of. Or ashamed of. If you are transparent that will leave your enemies as the only ones skulking around, conspiring, feeding and feeding off trial attorney dough for fear and profit.
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1. He sends a letter like this one to Roger Meyer of Best Practice which is a private for profit company that receives no federal grant money. But that's beside the point since the crime is now simply conducting and publishing research on any observation of any post market benefit of any drug for mental illness in peer reviewed publications such as JAMA. Which is what Fred Goodwin and Roger Meyer did along with authors from Kaiser Permanente and Group Health of Puget Sound.
(Suicide Risk in Bipolar Disorder During Treatment With Lithium and Divalproex
JAMA. 2003;290:1467-1473.)
The subject of Grassley's investigation is the following: " A Population-based sample of 20 638 health plan members aged 14 years or older who had at least 1 outpatient diagnosis of bipolar disorder and at least 1 filled prescription for lithium, divalproex, or carbamazepine between January 1, 1994, and December 31, 2001. Follow-up for each individual began with first qualifying prescription and ended with death, disenrollment from the health plan, or end of the study period."
The results?
In both health plans, unadjusted rates were greater during treatment with divalproex than during treatment with lithium for emergency department suicide attempt (31.3 vs 10.8 per 1000 person-years; P<.001), suicide attempt resulting in hospitalization (10.5 vs 4.2 per 1000 person-years; P<.001), and suicide death (1.7 vs 0.7 per 1000 person-years; P = .04). After adjustment for age, sex, health plan, year of diagnosis, comorbid medical and psychiatric conditions, and concomitant use of other psychotropic drugs, risk of suicide death was 2.7 times higher (95% confidence interval [CI], 1.1-6.3; P = .03) during treatment with divalproex than during treatment with lithium. Corresponding hazard ratios for nonfatal attempts were 1.7 (95% CI, 1.2-2.3; P = .002) for attempts resulting in hospitalization and 1.8 (95% CI, 1.4-2.2; P<.001) for attempts diagnosed in the emergency department.
Conclusion Among patients treated for bipolar disorder, risk of suicide attempt and suicide death is lower during treatment with lithium than during treatment with divalproex.
See how dangerous this is. No wonder Pharmalot rushed to blog on the Grassley "probe"
Worst Practice? Senate Probes NPR Host’s Firm
Of course, engaging in such activities in identifying risks is ok and individuals with such information should contact Grassley's office or the Church of Scientology or both. (Something tells me that either way the one will get the info to the other.
2. How did Phamalot find out. Turns out that Grassley, well before Roger Meyer even responded to the Grassley "probe" send what his missive to to the media in advance of sending the letter to Roger Meyer as well as bloggers such as pharmalot whose blog is an oasis for the anti-psycho-pharm crowd. Pharmalot then trumpets that Best Practice is being investigated by Grassley. Did Pharmalot contact Roger Meyer or Fred Goodwin or read the JAMA article in question. Of course not. Is such behavior defamatory. To my mind it is. When I have gone over the top -- and I have - I have at least apologized or issued a retraction. We will see what happens to Pharmalot in the days ahead. Even bloggers should abide by a code of moral decency.3. But don't hold your breath. The pharmalot blog along with others will generate more mainstream media headlines and articles. And a press release from Grassley that is already to go.
Will this have a chilling effect on the publication of off-label effects of medications. Of course it will. Will that harm patients and undermine innovation. Of course. Along with the assault on any tie between industry and academia.
The hijacking of science for fear and profit continues apace.
The U. S. Food and Drug Administration prides itself on being, first and foremost, all about science. So, how did the agency that regulates upwards of 30 percent of the
When one considers the mission of FDA—to independently protect and advance the public health—it is not at all clear whether the Commissioner should be a Senate-confirmed political appointee “serving at the pleasure of the President.” I think that the American people would prefer he or she be nominated by the President for a fixed 6-year term—similar to that of the Director of the FBI. Think about it—why should the safety of food additives, the integrity of the blood and vaccine supply, and decisions on drug labeling indications (to name only a few FDA responsibilities) be considered Democratic or Republican issues? The boss of the FDA Commissioner is and should continue to be the Secretary of Health and Human Services—a politically appointed, Senate-confirmed cabinet officer. This is enough. More politics just leads to regulatory paralysis and discord—neither which protects or advances
Having had the honor to serve our country as an FDA Associate Commissioner, I can unequivocally state that the unwelcome infusion of politics into science makes an already difficult job virtually impossible. To have the job of Commissioner open and only partially filled for extended lengths of time grinds progress to a halt. Low morale, lengthy delays, and even postponements often characterize an open Commissionership. This is not acceptable.
Who becomes the next FDA Commissioner is important. But an important indication of the seriousness with which President-Elect Obama takes that post is how soon in his administration a nomination is made. Let’s hope it’s done swiftly and smartly.
For more on this, have a look at the Journal of Life Sciences.
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.
