Thursday, October 18, 2012

Often, new treatments are no better than old ones

- Kenny Lin, MD

A recent systematic review and meta-analysis from the Cochrane Collaboration broke new ground in evaluating not one intervention or group of interventions for a single health condition, but the more general question of whether new treatments are more effective than established ones. The authors analyzed data from four cohorts of publicly funded trials of cancer treatments, treatments for neurological problems, and treatments for mixed diseases. In this sample, they found that slightly more than half of new treatments turned out to be better than old ones, but not by much: primary outcomes were just 9 percent better with the new treatments, and mortality fell by only 5 percent.

To make it easier for family physicians to compare new treatments to old ones, AFP publishes the STEPS (Safety, Tolerability, Effectiveness, Price, and Simplicity) series of new drug reviews. The October 15th issue includes a STEPS review of rivaroxaban (Xarelto), a new oral anticoagulant that is indicated to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation. Under Effectiveness, the review notes: "Rivaroxaban was as effective as warfarin at preventing stroke and systemic embolism, and reduced annual stroke rates to 2.1 percent, compared with 2.4 percent for warfarin. No trials have compared rivaroxaban with dabigatran (Pradaxa), a direct thrombin inhibitor, or with fondaparinux (Arixtra), an injectable factor Xa inhibitor." Rivaroxaban does not require laboratory INR monitoring like warfarin, but costs more than 40 times as much. Family physicians and patients will need to decide whether this relatively small benefit is worth the increased cost of this new drug compared to the old.

Wednesday, October 10, 2012

Why don't comparative effectiveness studies change clinical practice?

- Kenny Lin, MD

The October 1st issue features the third article in AFP's new series "Implementing Effective Health Care Reviews," a summary of the Agency for Healthcare Research and Quality's comparative effectiveness report on treatments for gastroesophageal reflux disease. Notably, the report found no differences in efficacy between proton pump inhibitors; better symptom relief from continuous daily compared with on-demand dosing; and limited data on endoscopic treatments. What are the chances that results from this and other high-quality comparative effectiveness studies will quickly change your practice? Not very good, unfortunately. As I wrote in an editorial that introduced the series:

To date, the track record of translating comparative effectiveness research findings into clinical practice has been mixed, at best. For example, several years after a landmark randomized controlled trial demonstrated the superiority of thiazide diuretics compared with other first-line medications for hypertension, prescribing of thiazide diuretics had increased only modestly. An evaluation of diabetes practice guidelines produced after the publication of an Effective Health Care review of oral treatments found numerous inconsistencies between guideline recommendations and evidence-based conclusions. Despite extensive evidence that initial coronary stenting provides no advantages over optimal medical therapy for stable coronary artery disease, more than one-half of patients who undergo stenting in the United States have not had a prior trial of medical therapy.

In the October issue of Health Affairs, Justin Timbie and colleagues propose five reasons that scientific evidence is slow to change how physicians practice:

1) Misalignment of financial incentives - e.g., fee-for-service payment systems tend to reward invasive therapies, such as surgery for back pain, that may be no better than conservative management.

2) Ambiguity of results - "Without consensus on evidentiary standards prior to the release of comparative effectiveness results, ambiguous results become fuel for competing interpretations, making it difficult for providers, insurers, and policy makers to act on the evidence."

3) Cognitive biases in interpreting new information - e.g., a tendency to reject evidence that contradicts previous strongly held beliefs, such as the superiority of atypical to conventional antipsychotics.

4) Failure to address the needs of end users - e.g., designing a study to compare the benefits of two therapeutic strategies, but not the harms.

5) Limited use of decision support - e.g., poorly designed electronic or paper patient decision aids that do not fit into the workflow of primary care practices.

Do these reasons sound about right to you? How do you think these obstacles could be overcome in order for front-line family physicians to rapidly incorporate the best scientific evidence into their practices?

Thursday, October 4, 2012

Who should receive medications for influenza?

- Kenny Lin, MD

Flu season is coming soon, and in addition to familiarizing themselves with the Advisory Committee on Immunization Practices vaccination guidelines for the 2012-13 season (offer influenza vaccine to everyone 6 months of age or older), physicians should consider how they plan to diagnose patients with suspected influenza. Despite the availability of multiple antiviral medications for influenza, whom to treat remains a challenging question.

In a 2010 Cochrane for Clinicians commentary, Dr. William E. Cayley observed that the neuraminidase inhibitors oseltamivir and zanamivir provided limited benefits for prevention and treatment of otherwise healthy persons with influenza. However, this conclusion was based on incomplete data - that is, results from published trials only. Subsequently, the Cochrane review authors were able to access several unpublished "clinical study reports" from the manufacturers and modified the review to reflect these additional data. In an updated Cochrane for Clinicians, published in the October 1st issue of AFP, Dr. Cayley finds that the evidence no longer supports using neuraminidase inhibitors to prevent influenza transmission:

The authors found that, based on clinical study reports, treatment with oseltamivir reduced the likelihood of an antibody response to influenza, the diagnostic marker that is typically used to determine the effectiveness of prophylaxis. In the absence of another way to measure the effectiveness of oseltamivir prophylaxis, it is uncertain whether the medication reduces the risk of influenza transmission.

Even for treatment of persons with influenza, the benefits of antivirals are modest: oseltamivir reduced the duration of symptoms by less than one day and had no effect on hospitalizations. Since these medications have side effects, physicians may reserve their use for persons at higher risk of complications, such as those with asthma or other chronic respiratory problems. As Dr. Cayley notes, existing guidelines are only as good as the evidence that supports them - and in the case of influenza treatments, not very good at all:

The contrast between the limited positive findings of this review and the strong support for treatment with neuraminidase inhibitors in public health guidelines (such as those from the CDC) highlights the importance of ongoing assessment of such recommendations and related educational materials, especially when evidence to support widespread implementation of an expensive intervention is lacking.