Monthly Archives: April 2012

Krumholz: “I think maybe we have a chance to turn the world upside down just a bit”

The Patient-Centered Outcomes Research Institute’s mission is to fund health research that offers patients and caregivers the information they need to make medical decisions.  The PCORI Board of Governors has adopted the following working definition of “patient-centered outcomes research.”

Patient-Centered Outcomes Research (PCOR) helps people and their caregivers communicate and make informed health care decisions, allowing their voices to be heard in assessing the value of health care options. This research answers patient-centered questions such as:

    1. “Given my personal characteristics, conditions and preferences, what should I expect will happen to me?”
    2. “What are my options and what are the potential benefits and harms of those options?”
    3. “What can I do to improve the outcomes that are most important to me?”
    4.  “How can clinicians and the care delivery systems they work in help me make the best decisions about my health and healthcare?”

To answer these questions, PCOR:

    • Assesses the benefits and harms of preventive, diagnostic, therapeutic, palliative, or health delivery system interventions to inform decision making, highlighting comparisons and outcomes that matter to people;
    • Is inclusive of an individual’s preferences, autonomy and needs, focusing on outcomes that people notice and care about such as survival, function, symptoms, and health related quality of life;
    • Incorporates a wide variety of settings and diversity of participants to address individual differences and barriers to implementation and dissemination; and
    • Investigates (or may investigate) optimizing outcomes while addressing burden to individuals, availability of services, technology, and personnel, and other stakeholder perspectives.

Listen to this inspirational speech by PCORI Board of Governors member Harlan Krumholz, at the PCORI National Patient and Stakeholder Dialogue, February 27, 2012:

http://youtu.be/sKOMDFnqkoY

Addendum:  see also these posts by Josh Freeman and Richard Lehman and articles in the April 18, 2012 issue of JAMA.

Harvard Faculty Advisory Council: cost of journals “prohibitive,” situation “untenable”

I’m taking the liberty of posting the entire text of this memo from the Harvard Faculty Advisory Council.  The suggested actions are particularly delightful.  H/T @PLoS.

To: Faculty Members in all Schools, Faculties, and Units
From: The Faculty Advisory Council
Date: April 17, 2012
RE: Periodical Subscriptions

We write to communicate an untenable situation facing the Harvard Library. Many large journal publishers have made the scholarly communication environment fiscally unsustainable and academically restrictive. This situation is exacerbated by efforts of certain publishers (called “providers”) to acquire, bundle, and increase the pricing on journals.

Harvard’s annual cost for journals from these providers now approaches $3.75M. In 2010, the comparable amount accounted for more than 20% of all periodical subscription costs and just under 10% of all collection costs for everything the Library acquires. Some journals cost as much as $40,000 per year, others in the tens of thousands. Prices for online content from two providers have increased by about 145% over the past six years, which far exceeds not only the consumer price index, but also the higher education and the library price indices. These journals therefore claim an ever-increasing share of our overall collection budget. Even though scholarly output continues to grow and publishing can be expensive, profit margins of 35% and more suggest that the prices we must pay do not solely result from an increasing supply of new articles.

The Library has never received anything close to full reimbursement for these expenditures from overhead collected by the University on grant and research funds.

The Faculty Advisory Council to the Library, representing university faculty in all schools and in consultation with the Harvard Library leadership,  reached this conclusion: major periodical subscriptions, especially to electronic journals published by historically key providers, cannot be sustained: continuing these subscriptions on their current footing is financially untenable. Doing so would seriously erode collection efforts in many other areas, already compromised.

It is untenable for contracts with at least two major providers to continue on the basis identical with past agreements. Costs are now prohibitive. Moreover, some providers bundle many journals as one subscription, with major, high-use journals bundled in with journals consulted far less frequently. Since the Library now must change its subscriptions and since faculty and graduate students are chief users, please consider the following options open to faculty and students (F) and the Library (L), state other options you think viable, and communicate your views:

1. Make sure that all of your own papers are accessible by submitting them to DASH in accordance with the faculty-initiated open-access policies (F).

2. Consider submitting articles to open-access journals, or to ones that have reasonable, sustainable subscription costs; move prestige to open access (F).

3. If on the editorial board of a journal involved, determine if it can be published as open access material, or independently from publishers that practice pricing described above. If not, consider resigning (F).

4. Contact professional organizations to raise these issues (F).

5. Encourage professional associations to take control of scholarly literature in their field or shift the management of their e-journals to library-friendly organizations (F).

6. Encourage colleagues to consider and to discuss these or other options (F).

7. Sign contracts that unbundle subscriptions and concentrate on higher-use journals (L).

8. Move journals to a sustainable pay per use system, (L).

9. Insist on subscription contracts in which the terms can be made public (L).

The “thermostat model” of health care utilization

Danil Makarov and colleagues have an interesting paper in the April 2012 issue of Health Affairs entitled “Appropriate And Inappropriate Imaging Rates for Prostate Cancer Go Hand In Hand By Region, As If Set By Thermostat.”  Using data from the SEER-Medicare database, the researchers examined regional differences in imaging for prostate cancer patients.  The SEER program of the National Cancer Institute collects information about cancer site, stage, and histology for cancer patients from sixteen geographic regions.  For cancer patients who are included in the SEER database and are covered by Medicare, information is available on Medicare claims for health care services.  The sample consisted of 48,148 prostate cancer patients aged 66-85 who were diagnosed with prostate cancer in 2004 or 2005.

The patients were divided into low- and high-risk groups.  According to the 2002 guidelines of the National Comprehensive Cancer Network, which were in effect at the time, high-risk patients should receive imaging such as bone scans, MRIs and CT scans under certain circumstances.  In low-risk patients, all imaging was considered inappropriate except CT scans for planning purposes in patients undergoing external beam radiation therapy.

The researchers found that overall rates of imaging varied among the different SEER regions.  Imaging appropriateness was not uniformly worse in regions with high rates of overall imaging.  Rather, regions with high overall imaging rates had higher rates of inappropriate imaging and higher rates of appropriate imaging.  Men with high-risk prostate cancer were more likely to receive appropriate imaging if they lived in areas with higher rates of inappropriate imaging.  The authors call this the “thermostat model” of health care utilization.  Dividing the regions into quartiles according to rates of inappropriate imaging of low-risk men, in quartile 4 (highest rate of inappropriate imaging), the odds ratio for men with high-risk prostate cancer receiving appropriate imaging was 1.75, with odds ratios in the next two quartiles being 1.48 and 1.04.

The authors state that their analysis suggests that

efforts to lower inappropriate use of imaging may simultaneously lower appropriate use of imaging because the two appear to be coupled.  Therefore, policy measures aimed simply at limiting inappropriate imaging in regions with high resource use could have the unintended consequence of decreasing imaging for those patients for whom such care is indicated. 

and

Policies will need to be multifaceted to break down the thermostat-like relationship between inappropriate and appropriate health care use.  Accountable care organizations will need clearly defined quality metrics for a broad range of conditions.  They will also need well-designed systems to ensure that the right patients are getting the right tests and procedures — and that costs are not contained at the expense of quality.  Cost-control policies must selectively educate providers to change their behavior and reduce the use of unnecessary care, while still ensuring appropriate care.  Such efforts could take on many forms:  profiling physicians who inappropriately overuse resources, linking payment to appropriate utilization criteria, or providing rewards and incentives to physicians and organizations that optimize resource use.

Danil V. Makarov, Rani Desai, James B. Yu, Richa Sharma, Nitya Abraham, Peter C. Albertson, Harlan M. Krumholz, David F. Penson, Cary P. Gross.  Appropriate And Inappropriate Imaging Rates For Prostate Cancer Go Hand In Hand By Region, As If Set By Thermostat.  Health Affairs 31:4 (2012).

Addendum 4/23/2012:  see also Jeff Levin-Scherz’s post on his Managing Healthcare Costs blog.

Lauer: is Qnexa a lemon or a peach?

Qnexa, a combination of phentermine and topiramate, is a proposed anti-obesity medication.  Although clinical trials demonstrate that Qnexa can lead to an approximately 10% weight loss, an FDA advisory committee recommended against approval in 2010 because of safety concerns (an increased risk of cleft lip and palette and increased heart rate, which could increase the cardiovascular risk).   On February 22, 2012, an FDA advisory committee voted 20-2 in favor of approval, based on an additional submission by the sponsor, Vivus Inc.

In a commentary in Annals of Internal Medicine, Michael Lauer of the National Heart, Lung, and Blood Institute explains why he voted against recommending approval.  Briefly, he discusses how the small pre-approval trials conducted by the sponsor, and the small number (12) of major cardiovascular events that occurred during those trials, give us insufficient information to determine whether Qnexa increases the risk of cardiovascular events.  Qnexa is thus like a used car that could be either a “lemon” or a “peach.”  In addition, based on prior experiences with obesity medications that were withdrawn from the market due to cardiovascular effects, we have reason to be concerned about an obesity medication that increases heart rate (consider the case of Meridia, previously discussed on this blog here and here).  Finally, the sponsor’s argument that certain improved biomarkers, such as blood pressure and high-sensitivity C-reactive protein, outweigh any effect of the increased heart rate, fails to assuage his concerns given the failure of surrogates in the past.  He states that “We cannot assume that just because a drug reduces weight and improves some biomarkers that it will be safe, let alone beneficial.”  I completely agree.  Here is his conclusion, but his commentary is open access, so I urge you to read it in full:

So what to do? We can resolve the information asymmetry by insisting on a large-scale, preapproval cardiovascular outcomes trial of Qnexa. It would be too risky to rely on postapproval surveillance or to hope that a rigorous trial could be conducted in a timely manner. If Qnexa prevents cardiovascular events, or at least doesn’t increase the risk for them, in a preapproval trial, then we will all know that we have the peach we’ve been waiting for.

More on the need for data sharing — the Tamiflu example

See my previous post on the need for data sharing.  For the past three years, a group of researchers has been trying to gather all of the clinical trial data for the anti-influenza drug Tamiflu (oseltamivir), without success.  As a result there is continuing uncertainty about the benefits — and harms — of the drug.  They tell their story in a New York Times op-ed and an article in PLoS Medicine.  Here is the summary from the PLoS Medicine article:

  • Systematic reviews of published randomized clinical trials (RCTs) are considered the gold standard source of synthesized evidence for interventions, but their conclusions are vulnerable to distortion when trial sponsors have strong interests that might benefit from suppressing or promoting selected data.
  • More reliable evidence synthesis would result from systematic reviewing of clinical study reports—standardized documents representing the most complete record of the planning, execution, and results of clinical trials, which are submitted by industry to government drug regulators.
  • Unfortunately, industry and regulators have historically treated clinical study reports as confidential documents, impeding additional scrutiny by independent researchers.
  • We propose clinical study reports become available to such scrutiny, and describe one manufacturer’s unconvincing reasons for refusing to provide us access to full clinical study reports. We challenge industry to either provide open access to clinical study reports or publically defend their current position of RCT data secrecy.

Also in PLoS Medicine, a response by a group of European drug regulators.  The regulators agree that that data secrecy is no longer acceptable but list some reasons for caution.

Peter Doshi and Tom Jefferson, “Drug Data Shouldn’t Be Secret,” New York Times, April 10, 2012.

Doshi P, Jefferson T, Del Mar C (2012) The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience. PLoS Med 9(4): e1001201. doi:10.1371/journal.pmed.1001201

Eichler H-G, Abadie E, Breckenridge A, Leufkens H, Rasi G (2012) Open Clinical Trial Data for All? A View from Regulators. PLoS Med 9(4): e1001202. doi:10.1371/journal.pmed.1001202

Here is a summary from Pharmalot.

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