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New Drugs Stir Debate on Rules of Clinical Trials


5 Star

New Drugs Stir Debate on Rules of Clinical Trials

Our Review Summary

A powerfully written account of how two cancer patients’ lives track the development of a promising cancer drug, this story does readers a great service by explaining the intricacies and ethical quandries of the clinical trial process. It does not serve them as well, though, in presenting clearly the evidence behind the drug in question: PLX4032. The reporter talked to at least 12 sources, many more than most stories we review, and went to lengths to explain that PLX4032 has generated a lot of hopeful talk but not a lot of proof. Still, by painiting such vivid portraits of the two main characters and inviting readers to truly fall in love with them, the story encourages readers to feel in the end that the patient who dies without taking the drug — without experiencing what the story repeatedly calls "the Lazarus effect" — has been victimized by an unjust and antiquated scientific process.


Why This Matters

The newspaper archives are full of stories about promising cancer drugs that went nowhere. As this story rightly points out, early success in reducing a patient’s symptoms does not mean a drug will increase a patient’s chance of long-term survival. Still, cancer patients naturally want to live as long as possible with as little pain and as much energy as they can. Chemotherapy, the main point of contrast in this story, can be an agonizing and ultimately fruitless experience. The thought that a drug might be providing patients rapid relief with fewer side effects is enough to make clinicians — and journalists — want to see the drug in the most hopeful light. To present readers with the best possible information about a complicated and confounding disease, we need to temper that hope with as much hard science as we can find. This story is about more than one drug or one disease. It is about the tension that exists in any randomized clinical trial. It is far more compelling when the disease is melanoma, but the ethical challenges raised by the study design hold true in a more generalized way. The clinician’s need to do what is best for his or her patient is at times in direct conflict with the need for a clear understanding of the societal value of the new treatment.


Does the story adequately discuss the costs of the intervention?


The story hints at costs, noting, for example, that one phase of the trials for the drug would cost $100 million. It also talks about how one of the cousins profiled in the story does not have health insurance. When the topic of health insurance was raised, the story could have helped readers by explaining how expensive chemotherapy is and how expensive this new drug is likely to be. There are competing drugs in the pipeline, and analysts for both Roche and Glaxo who would be willing to ballpark a figure. At the same time, the story is about a drug in its early development. Given what little is really known about the best approach (dose and frequency of administration) it is a bit early to be considering costs. We think this merits a satisfactory rating.

Does the story adequately quantify the benefits of the treatment/test/product/procedure?


This is not a numbers story. It is a story about ethics and the collision between science and emotion. Still, the story manages to show enough numbers to correctly characterize the limited scope of the early trials and the preliminary nature of the results. The relative value, at least based on the current data, is on target. PLX4032 appears to produce a response rate well in excess of that seen with dacrabazine to date. The story could have done a little better job comparing the two therapies, though. The first reference to the evidence says that "the company reported that month that nearly all 32 such patients in the drug’s first clinical trial, called Phase 1, had seen their tumors shrink." It says the drug "had halted tumor growth in 81 percent of patients for an average of eight (months)." That’s 26 patients. By comparison, the story says dacarbazine slowed tumor growth in 15 percent of patients for two months. This is a unfair comparison, given that the drug has now been on the market for many years and, as is often the case, has been shown to be less effective as the pool of patients has broadened. A better comparison, and more on point, would have been the number of patients and the percentage that had less tumor growth in the Phase 1 trial for dacarbazine. As the story says elsewhere, those trials were promising, too, but now the drug is helping just 15 percent of patients and for very little time.

Does the story adequately explain/quantify the harms of the intervention?

Not Satisfactory

The story should have broken down the evidence here, even if it was scant. It says that 81% of the patients in one of the trials improved. What percentage of them had side effects? And what about putting that into absolute numbers? A quick look at the published earlier trial shows that the drug is not without potential side effects. Approximatley 40% of the subjects enrolled in the trial required dose reductions due to side effects such as rash, fatigue and painful joints. It would have been even more important to note that about 30% of the subjects enrolled developed another less invasive form of skin cancer during treatment.

Does the story seem to grasp the quality of the evidence?


The story frames the debate over the trial nicely by explaining how the world has been fooled into the past by promising early results that did not end up extending patients’ lives. Whenever it talks about the actual science behind PLX4032, it includes phrases such as "the reprieve was all too brief: most saw their tumors begin to grow again within the year." It says later, "It was conceivable that when the cancer started up again, it would progress much faster in patients who had taken the new drug, wiping out any extra time they might have gained." Usually these statements are followed by a "but" statement, again raising the hope that PLX4032 might save more lives or at least make shortened lives more livable. On balance, readers will come away with the truth: that there is not a lot of evidence for this drug’s long-term success rate but that there is just enough to spark a serious conversation about rewriting the rules around clinical trials. One of the best aspects of the story is how it shows what happens when a trial does not follow the double-blind process. Because both the doctors and the patients know who is taking the promising drug (PLX4032) and who is taking the drug that has failed repeatedly (dacarbazine), they are forced into much more difficult conversations than doctors would normally be. In a double-blind trial, the patients would not be asking their doctors, "Why are you letting me die?" And then the doctors would not be going to oncology conferences and saying, "But if it was your life on the line, Doctor, would you take dacarbazine?"

Does the story commit disease-mongering?


Not only does this story avoid disease-mongering, it shows, with wonderfully descriptive language, how two patients can have very different experiences with essentially the same disease. "Mr. McLaughlin awakened with what felt like an explosion under his right armpit." The story manages to put melanoma into perspective (6th leading cause of cancer among young people) without resorting to hyperbole.

Does the story use independent sources and identify conflicts of interest?


The story quotes a dozen different sources on all sides of the discussion and, usually, makes it clear whether they are affiliated with the trial and, by extension, the drug manufacturer.We would have liked to have seen a little more exploration of some of the dissenting voices. If even Roche is wanting to push for a longer, more traditional trial, why are other clinicians and researchers second guessing that choice? The reasons given are that they love their patients and want them to suffer less. That may be, but one has to wonder if some of them might stand to benefit financially if the drug becomes part of a regimen that combines it with other drugs and other treatment regimens. This may be cynical, but at least some mention of whether any of the doctors quoted in the story have drug industry ties would have been good information.

Does the story compare the new approach with existing alternatives?


The story does a decent job contrasting PLX4032 with the main chemotherapy treatment, although, as noted above, it should have quantified both the benefits and harms better. The story also at least mentions that there are competing drugs being developed by other companies.

Does the story establish the availability of the treatment/test/product/procedure?


The story makes it clear that PLX4032 is under study and only available to those enrolled in a clinical trial. It walks readers carefully through all of the stages of the drug’s development. It could be required reading for anyone interested in the pharmaceutical industry or the regulatory apparatus.

Does the story establish the true novelty of the approach?


The story makes it clear that this drug is one of an emerging wave of drugs that are creating a lot of buzz in the cancer research community.

Does the story appear to rely solely or largely on a news release?


This story does not rely on a news release.

Total Score: 9 of 10 Satisfactory


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