AMA Finds Its Voice

• 06.12.2009

Healthy Stewardship

• 06.12.2009

Tonight I attended a dinner sponsored by the Aspen Institute's Health Stewardship Project that brought together a group of journalists, patient advocates and policy experts to discuss comparative effectiveness and the future of innovation.  (How did I get in?)  It was an off the record event but I can say for the most part that despite political and policy differences there was wide agreement that efforts to measure the value of new technologies should encourage innovation, not be generated by government alone but by robust partnerships, should promote healthy and long life, be controlled and easy to use by doctors and patients and not be used to control costs (however this latter objective will be harder to achieve if more health care spending is controlled by government.

There was less said about the role and impact of biomedical innovation on health care costs and society in general but here too there was agreement that more time and effort should be spent educating policymakers and the public about what innovation is and what it delivers. 

Aspen's Health Stewardship Project plays and should play an important role in making health and innovation the cornerstones of health care reform. 

Amen -- to the Max

• 06.10.2009

The Pink Sheet reports that, “Sen. Max Baucus, D-Mont., is now proposing that CMS or other HHS agencies could not immediately translate results of comparative effectiveness research into health care coverage policies, in CER legislation he introduced June 9.”

The "Patient-Centered Outcomes Research Act of 2009" - stipulates that HHS may use the outcomes of comparative effectiveness research in making coverage decisions "if such use is through an iterative and transparent process which meets the following requirements":

1) "Stakeholders and other individuals have the opportunity to provide informed and relevant information with respect to the [coverage] determination."

2) "Stakeholders and other individuals have the opportunity to review draft proposals of the determination and submit public comments with respect to such draft proposals."

3) "In making the determination, the [HHS] secretary considers (A) all other relevant evidence, studies, and research in addition to such comparative effectiveness research; and (B) evidence and research that demonstrates or suggests a benefit of coverage with respect to specific subpopulation of individuals, even if the evidence and finding from the comparative effectiveness research demonstrates or suggests that, on average, with respect to the general population the benefits of coverage do not exceed the harm."

The bill at strategic spots uses the language "comparative clinical effectiveness" as a means to emphasize that the research itself will not be cost focused, which Baucus noted is key to getting CER into health care reform.

How will comparative effectiveness research generate cost savings without any cost analysis?  According to Senator Baucus, cost decisions will be made by patients and providers. "It is up to them. It is not up to an agency to decide."

Decisions to be made by patients and providers (and in that order).  Now that's what I call "pay-as-you-go."

And amen … to the Max.

Sock it Toumi

• 06.10.2009

Since taking office in January, US President Barack Obama has taken a number of major decisions to control healthcare expenditure. Two of these should provide potentially significant savings with little investment:

The opening of the US market to follow-on biologics, or biosimilars, with estimated savings ranging from $12 billion over 10 years to $378 billion over the next two decades;^1-2

The lifting of the ban in the 2003 Medicare prescription drug act that prevents negotiation of the prices of medicines purchased for Medicare, and which incurs estimated extra costs as high as $30 billion annually.³

The efficiency of Mr Obama's third decision, to establish the Federal Co-ordinating Council for Comparative Effectiveness Research (FCCCER), is more doubtful. Mr Obama has dedicated $1.1 billion in the economic stimulus package for federal agencies to develop information on the comparative effectiveness of medicines. This decision aims to provide evidence to support value-driven decision-making. Such research is thought to be a potential source of cost-savings, permitting better care decisions to be made and an improved allocation of resources by Medicare, health insurers and even private individuals. The Congressional Budget Office has estimated an impact on healthcare spending of up to five times the total investment, not all of which would be visible as cost savings.

Two main arguments support Mr Obama's decision to create the FCCCER:

It is difficult to establish comparisons between products that have not been compared in head-to-head clinical trials. Such studies are rare because they are not required by the US FDA for products to be granted marketing authorisations. Furthermore, they present substantial risks to the drug manufacturers who have to pay for them. Bristol-Myers Squibb's PROVE-IT trial comes to mind.

Clinical trial data provide evidence in selected populations under experimental conditions ("internal validity") that might not reflect the true benefit of products under usual conditions of clinical practice ("external validity"). Pragmatic studies are expected to include a larger patient population to allow a combination of interventions and to reflect usual practice. They are expected to help patients and prescribers to select the most appropriate drug for individual cases.

Four research areas may generate data to allow comparative effectiveness studies: large-scale pragmatic trials, the use of databases, new quantitative methodologies and the design of complex quantitative models. No single area is favoured, although it is likely that large-scale pragmatic trials will capture most of the budget.

Yet many large clinical trials have failed to significantly affect medical practice. We can cite the following government-sponsored trials as examples:

CATIE, a National Institute of Mental Health (NIMH) trial in more than 1,400 patients comparing newer atypical antipsychotics with each other and with a conventional antipsychotic for the treatment of schizophrenia;

ALLHAT, the largest-ever antihypertensive trial and the second-largest lipid-lowering trial, with more than 42,000 patients enrolled; and

STAR-D, a seven-year NIMH trial aiming to define strategies to address treatment-resistant depression after failure to respond to a standard trial of treatment with an antidepressant medication.

The impact of these studies on actual clinical practice is debatable. One year after the CATIE results were published, 82% of clinicians treating schizophrenia indicated that they were unfamiliar with the results or that the results had not led them to change their clinical practice.⁴

In the two years following the publication of ALLHAT, the use of thiazide-type diuretics rose from 30.6% of the eligible population (uncomplicated hypertensive patients) to 39.4%, before falling back to 36.5% of patients.⁵ While the improvement was statistically significant, it remains far below the estimated total population that could benefit from such treatment.

STAR-D, meanwhile, did not provide conclusive results to alter medical practice.⁶ Thus large-scale trials are controversial, with debatable results and sometimes marginal impacts.

Following lobbying from the drug and medical devices industries, the Obama administration has clarified the potential use of comparative effectiveness research on reimbursement. The official conference report related to the bill specifies that lawmakers do not intend research to be used to mandate coverage and reimbursement policies for private or public payers.⁷ This makes real impact of comparative effectiveness research on pricing and reimbursement even less likely.
It would have been more effective to use taxes to provide an incentive for the development of Bayesian mixed-treatment comparisons and "complex systems" theory, applied to the field of public health sciences.

Bayesian comparisons can effectively address the lack of head-to-head comparisons between drugs. This well validated and recognised methodology remains underexploited in healthcare decision-making. Bayesian analyses can be used to make rapid and inexpensive comparisons that rank the effectiveness of alternative treatment options for a given indication. Furthermore, use of the technique will encourage the pharmaceutical industry to generate its own direct head-to-head evidence early in the drug development process.

Complex system analysis is already widely used in the physical sciences, meteorology, behavioural sciences and economics. Health outcomes and healthcare definitely obey the definition of complex systems, a new field of science that studies how the different parts of a system give rise to its collective behaviours, and how the system interacts with its environment. It is not possible to capture the actual outcome of a health intervention without integrating all the variables that contribute to it, such as healthcare policies, patient behaviour, the services offered, the societal attitude toward the disease and the insurance coverage. Such variables are currently treated as confounding factors whereas they are in fact an integrated part of the observed outcome.

New mathematical methods to support decision-making for complex systems have been developed, but they remain rarely used in public health. None of the most frequently used statistical methodologies, including propensity scoring (adjusting for differences in population sampling or confounding variables), addresses the complex system field in healthcare.

Clustering the assessment of the effectiveness of drugs assumes that the various health outcome components of an intervention can be analysed in isolation and that they are simply cumulative. Simultaneous analysis of all the factors that drive drug-related outcomes requires the use of complex systems sciences. This is the only way to support proper decision-making.

The cost of an indirect comparison performed by a consulting company ranges from $200,000 to $300,000. Such indirect comparisons are already used by European health technology assessment agencies, such as NICE in the UK.⁸ Investing $500,000 in complex system analysis would allow significant progress in analysing through different methodologies the results of studies already available. A lot of information that has already been generated and stored in data warehouses could be subject to this new analysis and would certainly yield new insights and deliver new benefits.

Without channelling effort into promoting these new methodologies it is likely that tax spending will continue to feed large and expensive pragmatic studies that bring little valuable information to support clear decision-making. Instead, alternative cost-effective methodologies should be encouraged through incentives for the development of comparative effectiveness. This would require a change of paradigm in drug effectiveness assessment. Yet this might well be the true challenge for the FCCCER if it wants to make best use of both the millions allocated to it and the historic opportunity to place comparative effectiveness research on the agenda of the life sciences sector.

References

6. S Hatcher. 'The STAR*D trial: the 300 lb gorilla is in the room, but does it block all the light?' Evidence-Based Mental Health, 11 (4), 97-99 DOI: 10.1136/ebmh.11.4.97, 2008

Professor Mondher Toumi is the chair of market access at the University of Lyon, France, and founder and president of Creativ-Ceutical, a strategic pricing and market access consultancy. Email: mondher.toumi@univ-lyon1.fr.

Revisiting the Dorgan Organ

• 06.09.2009

WASHINGTON (Reuters) - A U.S. senator on Monday said he dropped plans to try to add a measure allowing importation of lower-priced medicines from other countries to tobacco legislation after being told the Senate will consider the drug issue separately.

Democratic Senator Byron Dorgan said that Majority Leader Harry Reid had promised to bring the drug importation measure to a Senate vote "very soon." Dorgan said he expected the vote to happen within "a matter of a couple weeks."

Teddy Bares

• 06.09.2009

From www.keithhennessey.com ...

Over the weekend a draft of Senator Kennedy’s (D-MA) health care bill leaked.  After playing with Adobe Acrobat, here is the text of the draft Kennedy bill as a text file (173 K), and as a single Acrobat file (3.4 MB). Unlike the leaked version, both of these are searchable.

Calling it the “Kennedy” bill is something of an overstatement.  Senator Kennedy chairs the Senate Health, Education, Labor, and Pensions committee, and his staff wrote the draft.  By all reports, however, Chairman Kennedy’s health is preventing him from being heavily involved in the drafting.  Senator Reid has designated Senator Chris Dodd (D-CT) to supervise the process, but as best I can tell, it’s really the Kennedy committee staff who are making most of the key decisions.  For now I will call it the Kennedy-Dodd bill.

As the committee staff emphasized to the press after the leak, this is an interim draft.  I assume things will move around over the next several weeks as discussions among Senators and their staffs continue.  This is therefore far from a final product, but it provides a useful insight into current thinking among some key Senate Democrats.

Update:  I now have a three-page outline of the House Democrats’ health care bill.  I have a new post which contains all of the content below, and compares it to the House bill.  If you read the new post, you’ll get two for the price of one: Understanding the House Democrats’ [and Kennedy-Dodd] health care bill[s].

Here are 15 things to know about the draft Kennedy-Dodd health bill. 

1. The Kennedy-Dodd bill would create an individual mandate requiring you to buy a “qualified” health insurance plan, as defined by the government.  If you don’t have “qualified” health insurance for a given month, you will pay a new Federal tax.  Incredibly, the amount and structure of this new tax is left to the discretion of the Secretaries of Treasury and Health and Human Services (HHS), whose only guidance is “to establish the minimum practicable amount that can accomplish the goal of enhancing participation in qualifying coverage (as so defined).”  The new Medical Advisory Council (see #3D) could exempt classes of people from this new tax.  To avoid this tax, you would have to report your health insurance information for each month of the prior year to the Secretary of HHS, along with “any such other information as the Secretary may prescribe.”
2.  
3. The bill would also create an employer mandate.  Employers would have to offer insurance to their employees.  Employers would have to pay at least a certain percentage (TBD) of the premium, and at least a certain dollar amount (TBD).  Any employer that did not would pay a new tax.  Again, the amount and structure of the tax is left to the discretion of the Secretaries of Treasury and HHS.  Small employers (TBD) would be exempt.
4.  
5. In the Kennedy-Dodd bill, the government would define a qualified plan:
6.  
   1. All health insurance would be required to have guaranteed issue and renewal, modified community rating, no exclusions for pre-existing conditions, no lifetime or annual limits on benefits, and family policies would have to cover “children” up to age 26.
   2.  
   3. A qualified plan would have to meet one of three levels of standardized cost-sharing defined by the government, “gold, silver, and bronze.”  Details TBD.
   4.  
   5. Plans would be required to cover a list of preventive services approved by the Federal government.
   6.  
   7. A qualified plan would have to cover “essential health benefits,” as defined by a new Medical Advisory Council (MAC), appointed by the Secretary of Health and Human Services.  The MAC would determine what items and services are “essential benefits.”  The MAC would have to include items and services in at least the following categories:  ambulatory patient services, emergency services, hospitalization, maternity and new born care, medical and surgical, mental health, prescription drugs, rehab and lab services, preventive/wellness services, pediatric services, and anything else the MAC thought appropriate.
   8.  
   9. The MAC would also define what “affordable and available coverage” is for different income levels, affecting who has to pay the tax if they don’t buy health insurance.  The MAC’s rules would go into effect unless Congress passed a joint resolution (under a fast-track process) to turn them off.
   10.  
7. Health insurance plans could not charge higher premiums for risky behaviors:  “Such rate shall not vary by health status-related factors, … or any other factor not described in paragraph (1).”  Smokers, drinkers, drug users, and those in terrible physical shape would all have their premiums subsidized by the healthy.
8.  
9. Guaranteed issue and renewal combined with modified community rating would dramatically increase premiums for the overwhelming majority of those Americans who now have private health insurance.  New Jersey is the best example of health insurance mandates gone wild.  In the name of protecting their citizens, premiums are extremely high to cover the cross-subsidization of those who are uninsurable.
10.  
11. The bill would expand Medicaid to cover everyone up to 150% of poverty, with the Federal government paying all incremental costs (no State share).  This means adding childless adults with income below 150% of the poverty line.
12.  
13. People from 150% of poverty up to 500% (!!) would get their health insurance subsidized (on a sliding scale).  If this were in effect in 2009, a family of four with income of $110,000 would get a small subsidy.  The bill does not indicate the source of funds to finance these subsidies.
14.  
15. People in high cost areas (e.g., New York City, Boston, South Florida, Chicago, Los Angeles) would get much bigger subsidies than those in low cost areas (e.g., much of the rest of the country, especially in rural areas).  The subsidies are calculated as a percentage of the “reference premium,” which is determined based on the cost of plans sold in that particular geographic area
16.  
17. There would be a “public plan option” of health insurance offered by the federal government.  In this new government health plan, the federal government would pay health care providers Medicare rates + 10%.  The +10% is clearly intended to attract short-term legislative support from medical providers.  I hope they are not so naive that they think that differential would last.
18.  
19. Group health plans with 250 or fewer members would be prohibited from self-insuring.  ERISA would only be for big businesses.
20.  
21. States would have to set up “gateways” (health insurance exchanges) to market only qualified health insurance plans.  If they don’t, the Feds will set up a gateway for them.
22.  
23. Health insurance plans in existence before the law would not have to meet the new insurance standards.  This creates a weird bifurcated system and means you would (probably) be subject to a different set of rules when you change jobs.
24.  
25. The bill does not specify what spending will be cut or what taxes will be raised to pay for the increased spending.  That is presumably for the Finance Committee to determine, since it’s their jurisdiction.
26.  
27. The bill defines an “eligible individual” as “a citizen or national of the United States or an alien lawfully admitted to the United States for permanent residence or an alien lawfully present in the United States.”
28.  
29. The bill would create a new pot of money for state gateways to pay “navigators” to educate people about the new bill, distribute information about health plans, and help people enroll.  Navigators receiving federal funds “may include … unions, …” 

This would have severe effects on the more than 100 million Americans who have private health insurance today:

• The government would mandate not only that you must buy health insurance, but what health insurance counts as “qualifying.”

• Health insurance premiums would rise as a result of the law, meaning lower wages.
  
• A government-appointed board would determine what items and services are “essential benefits” that your qualifying plan must cover.
  
• You would find a tremendous new disincentive to switch jobs, because your new health insurance may be subject to the new rules and would therefore be significantly more expensive.

• Those who keep themselves healthy would be subsidizing premiums for those with risky or unhealthy behaviors.
  

• Far more than half of all Americans would be eligible for subsidies, but we have not yet been told who would pay the bill.
  

• The Secretaries of Treasury and HHS would have unlimited discretion to impose new taxes on individuals and employers who do not comply with the new mandates.
  

• The Secretary of HHS could mandate that you provide him or her with “any such other information as [he/she] may prescribe.”

A Commonality of Interest

• 06.09.2009

The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) have adopted a new policy regarding the disclosure of conflicts of interest.

Here’s the key paragraph:

“There is no inherent conflict of interest in the working relationships of physicians with industry and government.  Rather, there is a commonality of interest that is healthy, desirable, and beneficial.  The collaborative relationship among physicians, government, and industry has resulted in many medical advancements and improved health outcomes.”

What a unique perspective -- a "commonality" rather than a "conflict" of interest.

Bravo.

The complete AACE/ACE position statement can be found here.

Is Avandia Safe? Depends on Your Opinion of the Facts

• 06.08.2009

Some people will not take "yes" for an answer....

The results of the RECORD study would seem to vindicate the use of Avandia as a treatment option for diabetes patients seeking to maintain glycemic control and reduce the risk of death from cardiovascular disease....

RECORD: No overall increase in CV risk with rosiglitazone
Adverse findings include increased risk for fracture in women, heart failure
Posted on June 6, 2009

American Diabetes Association's 69th Scientific Sessions

Rosiglitazone was not associated with an increased risk for overall cardiovascular morbidity or mortality compared with standard glucose-lowering therapies, according to the final analysis data of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) study.

At 5.5 years, the primary outcome – first occurrence of CV death or hospitalization – was equivalent (14.5%) in patients assigned to rosiglitazone (Avandia, GlaxoSmithKline) or metformin and sulfonylurea, according to Philip D. Home, DM, DPhil, chairman of the RECORD Steering Committee and professor of diabetes medicine at Newcastle University, UK. The researchers reported 321 events among patients assigned rosiglitazone as add-on therapy and 323 events among patients assigned metformin or sulfonylurea only (HR=0.99; 95% CI, 0.85-1.16).

“Overall, in CV terms, the drug is safe. Would rosiglitazone meet current FDA criteria as a safe drug in diabetes? The answer to that is yes,” Home said during a press conference on Friday.

The RECORD study was designed to evaluate the long-term effect of rosiglitazone on CV outcomes and blood glucose control compared with metformin and sulfonylureas. The open-label study was conducted at 338 centers in 23 countries in Europe, Australia and New Zealand. The researchers randomly assigned 4,447 patients with type 2 diabetes who were already on metformin or sulfonylurea monotherapy to either add-on rosiglitazone (n=2,220) or a combination of metformin and sulfonylurea (n=2,227). All doses were progressively increased toward achieving and maintaining a target HbA1c of <7%. If HbA1c rose to 8.5% or more, either a third oral glucose-lowering drug was added (for rosiglitazone group) or insulin was started (for active control group).

Click here to read the full article.

So How do we explain this headline?

RECORD results: rosiglitazone doubles risk of heart failure, fractures
Publish date: Jun 6, 2009
By: Maude L. Campbell, Clinical Managing Editor

The much-anticipated results of the Rosiglitazone Evaluated for Cardiovascular Outcomes in Oral Agent Combination Therapy for Type 2 Diabetes (RECORD) trial seem destined to become yet another element in the agent’s controversial history.

Although rosiglitazone did not increase overall cardiovascular hospitalizations or deaths compared with metformin and sulfonylurea, the risk of heart failure doubled among patients taking rosiglitazone, and there were increased heart failure deaths, reports Philip D. Home, DM, chairman of the RECORD steering committee and Professor of Diabetes Medicine, Newcastle University, UK (pictured above).

And another point. Steve Nissen admitted, in the face of the RECORD evidence, that his initial meta-analysis might be inaccurate…

There were too few incidences of myocardial infarction and MI death among RECORD patients to detect a significant association with rosiglitazone. "I agree with the authors," says Steven Nissen, MD, chairman, Department of Cardiovascular Medicine, Cleveland Clinic. "The results of RECORD are inconclusive with respect to the effects of the drug on the risk of heart attack."

Dr. Nissen points out, however, that in the subgroup of RECORD patients with preexisting heart disease, there was a 26% increase (p=0.055) in MI.

Click here to read the full article.

I should point out, however, that Nissen’s meta-analysis swept everyone who used Avandia into his data pool to get his increase of risk (43 percent). Of course 26 percent is less than 43 percent.

Meanwhile, what havoc and public health impact was caused by the fearmongering…?

The Bankruptcy Myth: Of Conservative Definitions and Middle Class Debtors

• 06.08.2009

Reimporting Dumbness

• 06.05.2009

Let's see... new drug development is at an all time low and the FDA is faced with new responsiblities in tracking the safety of generics being produced from China, counterfeit products, tainted goods, the possiblity of developing new standards for follow on biologics...all in the name of safety. 

So the reasonable thing to do is...make it harder for the FDA to track a flood of products from other countries with shady track records?

Of course. Which is why drug reimportation has been reintroduced. Since Congress doesn't  really care about drug safety -- except when it comes to hearings -- the legislation designed to make it legal to tranship adulterated and counterfeit drugs through Canada and Europe (read the bill)  is now attached to a piece of legislation that would give the FDA the authority to regulate tobacco. (Just what we need, FDA approved Cuban cigars stinking up America.)

See this link to the In Vivo blog about drug running and get the whole story...