| |
IDEAL Study COMMENTARY- Doug Dieterich MD
A Healthy Dose of Curiosity
Clinical trial results require careful interpretation
|
| |
| |
Source: Liver Health Today (January-March 2008 Issue)
By DR. DOUGLAS T. DIETERICH, M.D.
Hardly a day goes by without important medical discoveries making news. Researchers discover a new molecule to treat a perplexing disease, new insight emerges about the course of a devastating illness, or a less invasive procedure proves to be as effective as major surgery. These types of advances are made possible by clinical trials.
For people living with chronic diseases such as hepatitis C, clinical trial results may offer insight into optimal treatment with existing medications or the promise of a new therapy. New research brings excitement, new hope and possibilities; however, the age-old wisdom "buyer beware" applies as much here as to any important purchase.
With the goal of beating their disease, improving quality of life or simply searching for a new alternative, people dealing with illness may be too eager to take clinical trial results at face value. If you read it, it must be true, right? But often there is a bigger picture, a broader context, or more information to take into consideration.
The classic example in medicine is an unproven therapy which claims "clinical studies show Drug A improves Condition XYZ." No doubt, a trial was performed and the drug exhibited the noted effect. But was Drug A compared to another drug? How many people were in the study? Were the results due to chance or is the effect real?
How does someone without a medical degree objectively assess clinical trial results and understand if the results apply to their own situation? How does a doctor decide which treatment is right for a particular patient? A critical eye and a healthy dose of curiosity - but not cynicism -- go a long way for both doctors and patients.
At the heart of sound medical advice is sound scientific evidence. Good evidence adheres strictly to the principles of good trial design and implementation, and it avoids use of misleading, inaccurate, or loaded language to describe the results. Good evidence is relevant to real-world practice. Good evidence shows no bias.
All studies are not created equal, and the way a trial is designed or the question it is designed to answer can have a major impact on how useful the results will be in everyday life. The next time you hear about some new medical research, think about the following questions:
Was the trial blinded? Did the researchers or subjects know which treatment they received? (If either group did, then their preconceived notions about each of the treatments being studied may introduce bias to the results.) How large is the study? Can the results be applied to the larger population of people with the same condition? Were the study subjects randomly assigned to treatment groups? If two or more treatments were evaluated, is it an "apples to apples" comparison? Are there aspects of the different treatments that may affect the outcome? Does the study accurately represent the standard of care or real-world experience? How clinically meaningful is the endpoint that was measured?
While these questions apply to all types of clinical trials, they are particularly relevant to "head-to-head" trials that pit one drug against another.
One real-life example occurred in the head-to-head comparison of two osteoporosis drugs, Fosamax and Actonel. The trial was designed to determine which drug was more effective at halting the deterioration of bone. While the results showed that Fosamax increased bone density more than its competitor, whether more bone density reduces the risk fracture - the ultimate goal in treating osteoporosis - is highly debatable. The resulting controversy was perplexing to patients seeking answers about this devastating disease.
Another timely example is the IDEAL trial, which compares three different hepatitis C treatment regimens of pegylated interferon and ribavirin. Results comparing the first two groups of patients - in which a high and low dose of Peg-Intron are given along with ribavirin - will indeed be beneficial because they should define the correct dose of Peg-Intron. This is the question the U.S. Food and Drug Administration (FDA) asked in requiring the company to conduct the trial as a condition of the drug's approval.
But the study enters dangerous territory with the addition of a third group of patients, which is intended to settle the question of which of two competing interferons - Peg-Intron or Pegasys - is "better." Although touted by the sponsoring company, Schering-Plough, as a head-to-head trial, this is really a misnomer. IDEAL can't determine which drug is better because patients in the Pegasys (produced by Roche) arm receive a different ribavirin regimen than those in the Peg-Intron arm. Not only do they receive a different starting dose of ribavirin, but the way ribavirin doses are reduced in the event a patient has side effects is also different.
Since ribavirin has shown to have a clear impact on treatment success for both interferons, the trial can't tell us anything about the differences between the two interferons. In addition, the study design isn't blinded, since both physicians and patients knew they were receiving either Peg-Intron or Pegasys - thus leaving the study open to bias. A real head-to-head trial controls all variables except for the intervention being studied.
These two different trials serve as important reminders for physicians and the public to look below the surface and to put the results into perspective. In each of these cases, it is easy to misinterpret findings, creating a bias against the medicine presumed to be inferior. As a result, patients may end up not receiving the therapy that may be best for them.
While individuals rarely have the tools or medical knowledge to evaluate research on their own, new studies provide the perfect opportunity to discuss treatment with a doctor. Physicians ultimately recommend a particular course of therapy not just on the findings of a particular study; they combine all sound scientific evidence with their own expertise and knowledge to provide each patient with an optimal treatment outcome.
Editors Note: Robert J. Consalvo, Schering-Plough's director of Global Product Communications and Advocacy Relations, issued the following statement in response to this column:
IDEAL was designed to meet the needs of the hepatitis C medical and patient communities to identify improved treatment strategies to optimize outcomes for patients. The study results will undergo a robust analysis with an independent review board and alignment with key stakeholders to minimize the perception of bias.
Schering-Plough believes IDEAL is a very important study and will help map how on-treatment responses at specific milestones, baseline patient demographics (viral load, weight, etc.) and predictability of response correlate to treatment outcome. The study also will help clarify how fast onset of action correlates to relapse rates and sustained response. These results will help guide physicians' understanding of which patients are most likely to respond better to which treatment.
It is important to note that the IDEAL results also will help guide development of future treatment paradigms. Several novel oral antiviral agents, such as protease inhibitors, are in development for treating hepatitis C, with the goal of improving sustained virologic response and shortened treatment duration. Peginterferon will continue to play an important role in as the backbone of therapy in new drug regimens for the foreseeable future.
Douglas T. Dieterich, M.D., serves as a professor of medicine (liver diseases) and as the director of continuing medical education for the department of medicine at Mount Sinai Center in New York.
|
|
| |
| |
|
|
|
