A Federally Funded Institute To Compare Drugs?
36 CommentsBy Ed Silverman // April 1st, 2008 // 10:13 am
That’s what two lawmakers are set to propose. Democratic Senators Max Baucus of Montana and Kent Conrad of North Dakota would establish an independent institute to systematically compare the effectiveness of drugs and devices, Reuters reports. Interestingly, the idea comes as the controversy continues to play out over Vytorin, which was found to be no better than the older and cheaper Zocor cholesterol pill, in reducing plaque build-up in a neck artery, a proxy for the risk of heart attacks and strokes, although the drug did lower LDL.
An analysis by the Lewin Group for the Commonwealth Fund found that comparative effectiveness research, used appropriately by doctors and insurers to guide decisions, could cut national health spending by $370 billion over 10 years. “One of the requirements for a market to work is that you have good information and we don’t have a lot of that right now,” Stuart Guterman, an economist at the nonprofit Commonwealth Fund, tells Reuters.
The bill is expected to propose funding of $200 million annually within five years. The institute would be governed by a board with officials from government, nonprofit groups, doctors, patients and industry. “Ultimately it’s better to target our health care dollars using comparative effectiveness rather than just cutting back because it’s so expensive,” Steve Wojcik, policy advisor for the National Business Group on Health, tells Reuters.
But the idea of the government funding independent comparative effectiveness studies has drug and device makers jittery, Reuters writes. They fear the info would influence insurance coverage and jeopardize billions of dollars worth of sales for their newest and most lucrative treatments. “We don’t want a situation where we’re going to a kind of ‘cheapest is best’ approach to medicine,” David Nexon, a policy expert at the AdvaMed trade group tells Reuters.
There’s more, but before you continue, we wonder what you think…
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Just the same, the idea has many backers, including economists, insurers and the nation’s large employers. That’s because US health care spending has tripled over the past four decades, and is now more than $2 trillion a year. Half of all long-term health spending growth is linked to technological advances such as new drugs and medical devices, according to the Congressional Budget Office.
At the same time, myriad reports have detailed how the quality of US health care trails other developed nations. “There is frustration that we are spending a lot and not seeming to get as much as we would like from that,” Gail Wilensky, a health economist and former head of the Medicare and Medicaid programs under President George H. W. Bush, tells Reuters. The US insurance system pays more for more care, encouraging docs to use new and expensive products, according to experts. And advertising is generally focused on the newest or most lucrative products.
But industry is worried that such comparative research could stifle innovation, if it turned into a treatment-denying mechanism. In a statement sent to Reuters, PhRMA wrote that it could back such research in concept as long as the results did not make “centralized value judgments” or be used to deny patient care.
A key sticking point for industry is whether the federally-funded comparisons would take costs into account, as is done in Europe. Lawmakers have said treatment costs would not be used initially by the institute, but these factors might be considered at some point in the future. “We really think the entity should stay away from cost-effectiveness,” Kathy Buto, vp of health policy at Johnson & Johnson, tells Reuters. “We’d recommend against an entity that would make up or down decisions.”
Some Republicans also embrace the idea. A House bill introduced last year was sponsored by Democrat Tom Allen of Maine and Republican Jo Ann Emerson of Missouri. Former Senate Republican leader Bill Frist, a physician, had also backed it. Wilensky, the former Republican official, says it’s wiser for drug and device makers to embrace an evidence-based research institute now, than to risk more random cost-cutting methods that insurers could employ.
As health care costs take a bigger bite of national spending - now 16 percent of gross domestic product and headed for 20 percent within a decade - payers will be forced to make hard choices of what treatments to cover. “Information can always be misused,” Wilensky said. “Learning how to spend smarter is so much better for them than the kind of crude mechanisms (insurers) will feel forced to turned to if we don’t go in this direction,” she says.
Source: Reuters
AV Block
Comparative effectiveness studies are a good idea, in theory. In practice, innovation proceeds ahead of such studies. Consequently, the real decision is whether these studies should be used (rightly or wrongly) to curb innovation, the largest source of healthcare cost growth. If they are used to curb innovation, then the public should be aware of this and decide in a democratic process whether curbing innovation is good for the country. To my knowledge, no politician has been honest about the innovation-cost tradeoff. Given the kinds of advances we’ve seen from biotechnology companies, I would be hesitant to kill the goose that laid the golden eggs.
Atlex
Ed, I think that this CE legislation would go well beyond drugs and also assess medical devices and procedures. The focus on drugs alone, while popular with some, could only accomplish but so much, since drugs are but ~11% of the healthcare dollar.
Ed Silverman
Hi Atlex,
Actually, yes, it would also cover devices. I just couldn’t fit that into the headline.
Cheers
ed
Nathan
Wouldn’t this be redundant research in many cases? We frequently compare our drugs to a competitor’s drug in clinical trials. Are government scientists more “trustworthy” than industry scientists? I don’t think so.
Anyway, thinking longer term, it will be unavoidable that our society needs to make cost-benifit analyses. Better to make these cost-benifit analysis with proper information than with guesswork. In that sense, it’s probably a good idea.
I thought this was a kindof funny statement: “An analysis by the Lewin Group for the Commonwealth Fund found that comparative effectiveness research, used appropriately by doctors and insurers to guide decisions, could cut national health spending by $370 billion over 10 years”
How in the world can they predict this? It’s entirely possible that comparative effectiveness research will INCREASE national health spending by conclusively showing that newer (name brand) medications ARE better older generic medications. Wouldn’t that be ironic…
John
No, there’s no redundancy. Comparative data is extremely rare, and rare on purpose. No one wants to develop a new drug only to show that it performs less well than established drugs. For example, Pfizer and Merck didn’t do the comparison studies on their cox-2’s (Celebrex and Vioxx) because the trials never hinted they’d perform any better. As a result, no one knew these drugs had the same pain relief capacity as Advil or Aleve yet cost over $100/bottle.
In some cases, more expensive drugs will be found to help more people, but that won’t be the rule. The dirty little secret of Big Pharma is that there really aren’t many new miracle drugs as promised, which is why that exec from J&J makes the hilarious comment about cost-effectiveness. I say her comment was funny because every new potential blockbuster is accompanied by “pharmacoeconomic models” to show how cost-effective it is. I laughed out loud.
I think we should build the new institute with an eye toward the future of healthcare: personalized medicine, stem cell research, biologics, etc. How will these new modalities fit in with such a scheme?
EEJ
Well, of course they’re nervous!
They’ve been rebranding older drugs with slight modifications, and not enough head-to-head trials with older versions, let along with other competing products.
I think it’s a great idea, as long as it is managed/overseen correctly. I guess that’s always the kicker with government programs.
Jack2
I don’t think Pfizer/Merck ever claimed improved efficacy with Vioxx/Celebrex. Ignoring the giant elephant in the room of cardiovascular toxicity with Vioxx, the drugs were promoted based on an improved GI-tolerability profile.
There’s more than one way to make a better drug.
Nathan
John,
You say: “the future of healthcare: personalized medicine, stem cell research, biologics, etc. How will these new modalities fit in with such a scheme?”
I’ll tell you:
1) Personalized medicine: It’s mostly fantisy and wordplay. Until genetic screening becomes cheap and widespread, there will be no “personalized medicine”. Even then, it will take years (decades) to get clinical trials designed such that a genetic profile of each individual is screened and compared to the efficacy & side effects.
2) Stem cells: largely fantasy — has about the same probability of success as gene delivery did 10 years ago. Embrionic stem cells often lead to cancerous legions while non-embrionic stems cells are pretty much a “shot in the dark”. (ie. “lets inject some stem cells into a spinal cord and see what happens”)
3) Biologics are really no different than small molecule drugs, except that currently there is no generic equivalent that is possible. (that will change sooner rather than later I think) Biologics usally interact with the same targets as small molecules do. They block pathways and enzymes just like small molecules. There are a few exceptions (i.e. insulen, epogen)…
That leaves us with small molecules. They aren’t going anywhere. They have been the bedrock of pharmaceuticals for 100 years — and I truely believe that they still will be the bedrock of pharmaceuticals 100 years from now.
Outside the Box
Let’s suppose this goes ahead and is funded to the tune of $200m per year. I don’t know that much about the detail of running these kinds of trials, but I do know a lot about using data to identify comparisons between products and we have a very large problem - which drugs get tested head-to-head? Take statins - Lipitor/Zocor, Lipitor/Crestor, Zocor/Crestor, all of the above v’s Vytorin, all of the above v’s the next new drug? Assuming that this is not what is being proposed (mainly because it wouldn’t work and would be too costly) the question comes back to which drugs get tested?
My guess (given the tenor of the proposal) is that the drugs being tested would come from the classes of drug where the total drug cost per year is highest and the differential in price between highest and lowest priced product is largest. In other words - clinical trials to manage drug costs NOT to identify true efficacy/safety comparisons.
There is a much better way of achieving the desired endpoint here. Get the FDA (and other regulatory bodies) to require Phase III studies that include a comparison with the established “Gold Standard” as part of the approval process. This establishes a clinically (and financially) meaningful comparison that can be used to identify the key characteristics of the new product. Secondly, establish a proper clinical medical record system that can be properly analyzed to identify the in-patient performance of existing products. This way every product on the market can be examined and analyzed in terms of actual usage rather than the false setting of a trial, with comprehensive analytical techniques being used to identify any meaningful differences in the ways that drugs within a class are being used.
AV Block
Outside the box -> safety and efficacy are onerous enough hurdles… adding more requirements will only delay new drugs. Additionally, there are ethical considerations in properly sizing such pre-market trials. Best to conduct comparative trials in a post-market setting, either randomized or large-scale observational studies.
There are so many comparisons that need to be made, so a drawback is that it is too costly to conduct enough trials. The fear that I have is that the absence of comparative data for technology X would be interpreted as insufficient data for reimbursement. As I alluded to earlier, technological progress could be hindered if such information is interpreted incorrectly. This is a cost that is very difficult to quantify.
AV Block
Sorry… just to clarify… you have to be parsimonious in running comparative efficacy studies in a pre-market setting, because you are enrolling human subjects into scientific experiments… ethical considerations need to be weighed.
James
I’m actually for this institute.
Normally, the thought of government getting bigger sickens me. And it does here, as well.
But if we are going to have the government (taxpayers) paying for healthcare (currently paying a significant portion via Medicare, soon to be all if/when a democrat gets into office), they should be doing comparisons. And they SHOULD be taking into account cost. It’s bad enough if I have to pay for your healthcare–I sure as hell shouldn’t have to pay for you to get the best healthcare.
Socialized Medicine–where you get what you pay for. ™
Dan
Another alternative solution would be to compare drugs awaiting approval to other medications instead of a placebo, which is the requirement at this time.
Choklad
I doubt whether this would have a cost implication in the next five years as so many of big pharma’s top blockbusters are coming off patent anyway.
However, it could have real potential in the next 10-20 years if combined with phase 0 clinical trials & other outcomes from the FDA’s Critical Path Initiative
http://www.fda.gov/oc/initiatives/criticalpath/
This would allow comparative effectiveness studies for different patient subgroups as defined by their genomic or proteomic biomarkers.
http://www.nature.com/nrd/journal/v6/n4/full/nrd2251.html;jsessionid=02E991828FEDA2EE9D4C127885907622
Some of the smarter Pharma companies already realise this and are working towards evidenced based medicine.
In fact yesterday Novartis and the FDA completed a two-year Cooperative Research and Development Agreement (CRADA)
http://www.pharmalive.com/News/index.cfm?articleid=527033&categoryid=56
If this tentative legislation was put together with a Medical Innovation Prize Act
http://thomas.loc.gov/cgi-bin/query/z?c110:S.2210:
instead of the current pricing & reimbursement arrangements then we’d have better & cheaper medicines for all.
Justice in Michigan
Lots of interesting angles here. Just on one question related to point that Nathan raised - yes, both Vioxx and Celebrex wanted to claim GI benefit. That was, of course, the point of the VIGOR study. (And CLASS which had more an even more interesting history in some ways.)
But Q. for Nathan or anyone: Why do you think Aleve was chosen as comparator in VIGOR? Is it, in fact, known for more GI issues than ibu? Or used more commonly by relevant population?
Outside the Box
AV Block - sorry I disagree. I think that there are more serious ethical questions giving patients a placebo than giving them the currently recognized gold standard therapy. We are using a regulatory approval process that is designed for the science of the seventies. Not only should we drop the placebo comparison but we should also switch to Bayesian analysis instead of statistics to identify the real safety/efficacy/benefit profile of the product.
Also it is precisely the volume of comparisons that need to be made that requires us to think differently about the solution.
Nathan
Outside the box,
It is my understanding that for serious diseases (ie cancer, AIDS, etc) that clinical trials compare drugs to the currently recognized standard of care — not to placebo. It would be nearly impossible to enroll someone in a cancer clinical trial if the patient knew that there was a 50% chance they were recieving placebo. The same is true for antivirals. Current AIDS and HPV drugs are compared with the standard of care — not placebo. Take the Vertex HCV drug in clinical trials as an example (Telaprevir). They are in phase III trials. They aren’t comparing it to placebo — they are comparing it to gamma-interfuron, which is the standard of care for HCV.
Can anyone with more first-hand experience in clinical trial work comment on this?
Melody
rDNA insulin–the first biotech drug–was approved using precisely that “science of the seventies.” The only comparative studies used a single species of natural insulin to validate that rDNA insulin behaved in a similar manner; then all comparative studies ceased. For two decades diabetics have been subjected to this ‘better’ product; outcomes have not improved; longevity has not increased; and with the broken AER, we cannot know any truth about safety matters. The truth is, to this day, we can’t even guarantee ‘what’s in the bottle marked insulin.’ We KNOW that synthetic insulin is not an exact copy of human insulin; nevertheless, it has been marketed as such. Will an institute (such as proposed) have the capacity to determine whether this drug is a small-molecule drug, a biotech drug, and get answers that were sadly missing because it was the “first of its kind”?
Dr. Sal Giorgianni
The March 20th Editorial in The New York Times commented favorably on this proposal. The following is my published Letter To the Editor of March 24th on this important topic.
“Your Editorial perspective of March 20, 2008 about proposals to provide information independent from commercial bias on the appropriate use of medications is quite right. Pharmaceuticals are very important technologies and the imperative to provide alternative resources for information about their proper use is not a new issue. As a former hospital-pharmacist and pharmaceutical company executive now turned academician I know firsthand how important having non-financially biased information is and how difficult it is to provide.
The current proposal is, on the surface, most interesting as it would stimulate and supports multiple independent approaches. Bias in review about the utility of any technology is inevitable however, bias is not inevitably inappropriate. Expert opinion is just that, opinion. Creating a system that allows for multiple-expert review, independent of any inventor, provider, purchaser or fiscal intermediary would help to mitigate bias primarily based on financial concerns and allow for balanced expert perspectives. Universities independent of medical centers, and thus with no fiduciary interests in opinions about these technologies, are one readily available and appropriate resource for this work.”
JM
Isn’t AHRQ the federal agency that already has this as part of their mandate? http://www.ahrq.gov/about/mmarsrch.htm
Am I missing something?
AV Block
Outside the box, you are wrong. To demonstrate drug X is superior to drug Y would generally require the enrollment of a lot of patients - costly and unethical. I did not rule out the possibility of non-inferiority trial design, which would rule out testing drug A versus placebo. Moreover, I am also in favor of adaptive clinical trial design - draft guidelines exist for devices to my knowledge, but not for drugs. However, adaptive clinical trial design is not a panacea in the evaluation of new drugs. Also, adaptive clinical trial design also introduces issues such as prior - any two people can reasonably disagree what that prior actually is.
At the end of the day, we are avoiding the real issue - the tradeoff between technology and cost.
AV Block
Patients aren’t guinea pigs. Randomized controlled trials of superiority are costly. Parsimonious is good / ethical. And Bayesian clinical trial design won’t entirely solve the problem and will create other problems. Surely Bayesian statisticians would disagree with me…
Bob Freeman
Justice, from my days in doing outcomes trials on NSAID safety we usually used either diclofenac or naproxsin (Aleve) as the active controls because their safety profiles are very good. Ibuprofen is also quite safe but declofenac had greater use globally.
Bob Freeman
Just a couple of comments: I recall discussions of this type going back at least 15 years; viz., creating a quasi-public or public authority to serve either as a clearing house or a research institute for these types of studies. AHQR has had some of this under its authority but its scope has far exceeded drug therapy alone.
Comparative effectiveness is hard to do for a couple of reasons: current practice may be different from standard therapy reported in clinical literature. Doses evolve over time and selected a relevant dose can be as controversial as selecting the most relevant comparator. Re cost effectiveness, price changes due to new market entrants and drugs going off patent within the therapeutic class render conclusions ephemeral at best.
I’m not discouraging the initiative but I do see logistical difficulties both in establishing the authority and in the conduct of trials. The public comment alone will be voluminous.
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HorusCat
Nathan, Out of the Box, et al.,
Maybe I’m missing something here, but it seems to me this would discourage R&D. Why would a company sink $1 billion into developing a new drug, only to find in the end that it works no better than existing drugs, and therefore, won’t be accepted?
And wouldn’t comparisons get really tricky with CNS drugs, where there is such variability in individual patient response?
Tanin
HorusCat,
To a certain extent you are right about this proposal discouraging R&D, however it is more likely to discourage the development of “me-too” drugs than truly innovative therapies.
Also using other countries as a model (Australia etc), if a new drug is found to be no better than an old drug they normally can be reimbursed on a cost-minimisation basis (ie same price or lower than old drug), so the pharma company would recoup some of their research losses from developing the drug
Nathan
I think Bob brings up one of the most important points of this discussion: What doses will be compared? In many cases it will be very easy for a company to say “The competition’s drug worked better, but if our drug were given at a truely comparable dose it would have been equivalent or better.” So then you are in a position of having to study multiple doses. We also have 3 or 4 very similar products in a given theraputic area. This quickly becomes an unsolvable problem — do we really study 10-15 subgroups? If so, this becomes either VERY EXPENSIVE (due to clinical trial size) or irrelevant (due to limited subgroup size).
Outside the Box
And pretty much all of the above comes back to using placebo as it is the only unvarying control.
To be clear, I am wholly against the idea of setting up prospective controlled trials for the purpose of comparing drugs. I think the idea is only workable in disease areas where the disease is non-life threatening (ethical issues), where the safety profiles of the drugs are already sufficiently well established to avoid issues (ethical), where the disease has lots of patients (recruitment, time, cost) and where the effects of products differences can be reasonably balanced (i.e. dose differentials and so forth).
Bob is correct, this has been discussed numerous times over the years all over the world and different solutions have been put in place (ref Australia, UK). For the US market both of these are bad examples because of the different payer systems (both) and the lack of any significant indigenous industry (Australia).
I come back to the original announcement, and it is clear that the real objective here is cost containment. From a healthcare perspective it would be far more interesting to explore the damage done from non-compliance and lack of persistence because I think that there is where we find that the real costs to the economy will be found. What is the point of proving that Crestor is better than Lipitor if patients only comply with their meds for 6-9 months and over half the patients have stopped taking drug entirely within a year?
HorusCat
All,
Sometimes a me-too drug is better, while not being more efficacious, because of dosing convenience or side effects…a good example is Mevacor vs Lipitor…
And OTB is absolutely right–sometimes I can’t figure out where all these drugs cost come from, because industry figures show no one is compliant with their meds!
snugpharma
The money would be better spent on increasing the FDA funding to facilitate its mandatory role. That is where the common denominator sits. These government employees with talent deserve a better deal.
Richard Leff
This proposal sounds radical but a model already exists. The NCI funds several large cooperative oncology research groups that perform studies based on need assessed by the clinical leadership of the groups. (They also perform some studies spnsored by industry.) They also perform very large national inter-group studies encouraged by the NCI. Some of the studies have included comparisons of 2 approved drugs or different administration regimens and are studies that industry has no incentive to perform. A great example is ECOG 1199 comparing paclitaxel to docetaxel in 2 different administration schedules. A model that would allow the NIH to sponsor independent research by large cooperative groups in other disciplines could only advance patient care.
Justice in Michigan
I guess it cuts in all directions. As I understand it, SP balked at doing comparisons between Claritin and existing allergy meds because of the anticipation it would lose on efficacy unless you raised the dosage - in which case, it would lose on “doesn’t make you drowsy.”
That may or may not be true in this case. But, in general terms, one comes to the question of what is the proper balance between what sells and what’s true, who is responsible for finding out, and who pays (and in what ways) when we don’t find out.
Scott
Actually, I am surprised that a proposal like this isn’t actively supported by the healthcare insurance industry, since they fund most drug purchases — presumably under the assumption that these substances improve patient health. Having a more “objective” review would help ensure that healthcare providers aren’t unncessarily funding expenditures that do not have proven benefits. Now, what is the official opinion of United Healthcare, Humana, Aetna, Cigna and the other major providers on this subject?
Atlex
Scott for the most part, the health insurance industry does support this. BCBSA, representing the Blues, has been an active supporter. However, they, like others, realize the potential corruption of this concept. The Center could become something like DERP out of Oregon, which is simply an exercise in cost minimization. Or, the Center could get bogged down in an academic exercise that produces little of value. And, there are many other possibilities for corrupting the system–all depending upon the point of view (ie, bias) of who one speaks to. One would hope that the Center would base its work on a robust and acceptable definition of “value”; however, I have my doubts as to whether this is possible.
LILLI
I cannot support this. Every time the government deceides to help it is not genrally for the public but it is for the medical profession, healthcare industries and hospitals. Just the same with Patient Safety Acts were in name only, but not to do anything with patient safety. Patient Safety was concern for the doctors, healthcare industries, hospitsals, pharmaceuticals being sued. Now, patients that have legtimate medical malpractice case find it difficult to find a lawyer that will represent them. First we must change and put restrictions on our elected officials. Having representatives in congress for more than 46 years is not a good idea. We need to change the corruptiion in our government. New Jersey Clean Election Act also was in name only. Just last week the legislature and Gov. Corzine
reported issues that New Jersey /clean Act is a farce. In fact, New Jersey taxpapers money was wasted on this corrupt program.