TASK DEFINITION: Generate an explanation for the given claim using the provided supporting material from the paragraph. Please consider the following points while generating an output. 1) The claim will always have supporting proof in the paragraph, and the paragraph will have a clear point of view supporting the claim. 2) There can be instances where direct correlation to the claim is not available. Make use of the sentences in the paragraph to provide a corresponding output supporting the claim. 3) The explanation should be at least one and at most twelve sentences long.
PROBLEM: Paragraph: This release makes no mention of the costs of the drugs compared in this study, even though the drugs have been in use for years and are widely available. Since the study is a comparison of various treatments for this form of cancer, it seems relevant to offer a cost comparison as well as a comparison of efficacy. It appears that the high dose methotrexate is given over a 24-hour period, presumably in the hospital, while the standard methotrexate is given as a single dose. Also, the high dose methotrexate is followed by leucovorin administration while the standard dose is not. According to the site GoodRx, the cost for methotrexate in low-dose (2.5 mg) pill form averages out to about $50 for a month’s supply. Newer, injectable variations of the drug cost upwards of $500 a month for the 25 mg dose. The release states that patients receiving high doses of the drug methotrexate “had a significantly better outcome, by 5 to 6 percent” than did patients receiving the current standard of care, which is gradually escalating doses of the drug. The release also explains that patients nine years old or younger who were also treated with a steroid called decadron (dexamethasone) for half as long as normal (14 versus 28 days) benefited from the treatment while patients 10 and older did not. We’re not sure of the meaning behind these results as portrayed in the release. Which outcome was better by 5 or 6 percent? The study has several. Does that mean the relapse rate was reduced or is it the event free survival that was better? It would be more meaningful to readers if the release had included the actual relapse and event free survival rates for each group analyzed in terms most people can understand. For example: “relapse rates were 5 percent lower in Group X compared to Group Y.” We’ll give this category a satisfactory rating largely due to the release including information that patients 10 and older receiving dexamethasone “were at much higher risk for a debilitating bone condition called osteonecrosis,” although we would have been happier if that greater risk would have been quantified. However, the published study explains that there were toxicity problems beyond that of dexamethasone and the release would have been stronger including that information as well. The release stated the study was randomized and controlled, and provides a broad overview of the study design, for which we give the release a borderline satisfactory under this criteria. However, these are the superficial results. On deeper delving into the study methodology, the statistical significances of the results were very close to not statistically significant. This is due to their planned interim stopping of the treatment and the fact that they were looking at multiple outcomes in multiple groups. This release doesn’t demonstrate disease-mongering. While the release does say that this clinical trial was run by the Children’s Oncology Group, which is funded by the National Cancer Institute and the National Institutes of Health, it makes no mention of possible conflicts of interest. Compounding that is the fact that the published study says, “Disclosures provided by the authors are available with this article at www.jco.org,” but that information is behind the journal’s paywall for most readers, so it’s unknown if there is, or is not, a conflict. It appears as though five of the authors (out of a total of about 20) have some conflicts of interest, mostly from several types of drug company payments. The release is comparing the efficacy of treatment regimens using different drugs so alternative treatments for B-acute lymphoblastic leukemia are noted. The release makes clear at the end that the treatment of this disease is improving thanks to refinement of the use of existing drug treatments, meaning that they are readily available for patient use. The release suggests the study findings could change the way childhood leukemia is treated. Modifying existing treatments to enhance a patient’s survival is certainly novel enough to warrant a release. There is no use of unjustifiable language in this release. However, the tone may be a bit overly optimistic given the study findings. Claim: Relapses of childhood leukemia improve with high doses of common chemo drug

SOLUTION: This release reports the findings of a large clinical trial testing whether alternative dosing regimens of standard chemotherapeutic drugs can improve the treatment of B-acute lymphoblastic leukemia. The study showed that using high doses of the drug methotrexate, rather than the standard regimen of gradually increasing doses, improved the outcomes for patients with the disease. The study also showed that using the steroid dexamethasone increased a debilitating bone condition in patients 10 and older but not in patients nine or younger. While the study results are promising, they are by no means clear-cut in the release. The release needed some qualifiers in order to give a clear picture of the benefits. The release also neglected to discuss costs and potential conflicts of interest among the investigators. This form of cancer — B-acute lymphoblastic leukemia — is the most common cancer in children and a major cause of cancer death in patients under 40 years old. And while the majority of patients survive with appropriate treatment, anywhere from one-fifth to one-quarter of patients do not. This study showed that refining the dosing of standard cancer drugs may improve the outcome for some high-risk patients.

PROBLEM: Paragraph: The release does not mention cost. The FDA evaluates drugs without consideration of cost, so it’s understandable that they wouldn’t comment on it — and that’s why we’re rating this Not Applicable. But let’s be real here: The value of a new drug is a function not just of how well it works, but its cost-effectiveness. So we look forward to the day when any news release about a new drug — even one from the FDA — will include some mention of cost in its message. This release gives the preliminary results from a single study of 310 patients. Because the drug is experimental, long-term results haven’t been studied. Of the 310 patients enrolled in the lone trial upon which the approval is based, 14.8 percent showed some shrinkage of tumors during the assessment period lasting from 2.1 to about 13.8 months. For a subset of patients who were classified as having a positive response to PD-L1 expression, the response was 26 percent. As noted above, tumor shrinkage doesn’t always lead to improvements in survival or quality of life. It is a surrogate endpoint — a substitute — for the main outcome which is survival. Although this drug looks promising, to be fully transparent about its benefits as currently known, the release should have explained this. As noted in the “Summary,” another larger study is underway to assess the drug’s impact on extending life and improving quality of life. The release includes a description of side effects of this treatment. The most common ones included fatigue, decreased appetite, nausea, urinary tract infection, fever (pyrexia) and constipation. The release also mentions that patients taking the drug have an increased risk of infection and serious side effects that are “immune-mediated.” We would have liked a bit more context on what this term means for patients. The release outlines that this is the very first clinical trial of this compound for safety and efficacy, and under which regulatory paths the drug was assessed, including “breakthrough therapy designation, priority review status and accelerated approval.” We’re giving this release the benefit of the doubt and rating it Satisfactory for its bare bones description of the trial (and since we already addressed the lack of long-term survival data in the “Benefits” section.) As it stands, the results from the small trial were preliminary and short-term and did not reflect long-term survival. We would have liked to see a reference or link to the completed trial where one could look at the results to assess independently or learn more about the outcomes. We think the release should have provided more data on the patient demographics, the treatment regimen (dosing amount and schedule) as well as the range in tumor reduction. There is no disease mongering. This release describes the approval of a new drug by a regulatory agency, but we’d still like to know who sponsored the study that’s the basis for the approval. It’s not enough to state who markets the drug. The release does not give us very much information about alternatives. These patients had already received other therapy and their cancer had recurred, so it is implied that they had no other alternatives. But this isn’t stated very clearly. We can assume (and it seems evident) that the platinum-based therapy that the patients didn’t respond to initially is the usual treatment. The FDA’s approval of a drug clears the way for the drug sponsor to scale up production and begin marketing and selling the product. (The FDA doesn’t state this explicitly but it can be inferred.) A NYT article said the drug would be available in about two months. The release clearly states this product is first of its kind for this type of cancer. We found no unjustifiable language. Claim: FDA approves new, targeted treatment for bladder cancer

SOLUTION: The Food and Drug Administration approved a new immunotherapy drug that acts as a “checkpoint” inhibitor in patients whose bladder cancer (urothelial carcinoma) has not responded to other chemotherapy. The drug, atezolizumab (marketed as Tecentriq), showed effectiveness in about 14 percent of 310 patients in a very preliminary study. The release notes that the trial measured tumor shrinkage as the main outcome. It didn’t note, as a NYT article did, and important for this type of trial, that it is unknown whether the treatment makes a difference in survival. A larger study is being done to examine this. Whether it makes a difference in quality of life is also important and will presumably be examined in the larger trial. The National Cancer Institute (NCI) estimates 76,960 new cases of bladder cancer and 16,390 deaths from this disease in 2016. This approval of a new drug for treating bladder cancer is part of a wider area of research into immunotherapy, in which drugs target mechanisms of the human immune response. Patients with the PD-L1 protein highly expressed in their tumors appear to be responding best to the drug. This drug is an example of targeted chemotherapy which is becoming more important as treatments can be fine-tuned to the cancers of individual patients. In patients with intractable cancers, immunotherapy appears to offer some new hope while also bringing sobering questions about affordability and disparity of access by income. The drugs are typically very expensive — with some estimates putting the treatment cost for a single patient as high as $1 million. When the FDA gives a compound a “breakthrough” designation, some physicians and patients can misunderstand what that means. That’s a topic recently explored in this post.

PROBLEM: Paragraph: The story includes some pricing estimates for these products. The story is clear that – despite the claims made by some who stand to profit – there is no quantifiable information about benefits documented about these products. And there’s this closing skepticism from Dr. Lewy: “he was not sure that their other purportedly sleep-inducing ingredients like valerian root work and partly because food delays rather than hastens the absorption of melatonin.” The story explains that dessert makers “are marketing their products as a harmless way to promote relaxation.” While harms are not quantified, it’s clear from the story’s discussions about regulatory questions why that’s impossible to do right now. The harms mentioned are largely hypothetical in that there isn’t good evidence documenting these problems. But the story does a good job in painting, with broad strokes, what might go wrong if one uses these products. The story shows how evidence is elusive, partially due to the lack of regulatory clarity about the products in question. No disease-mongering in this story. Several independent experts – independent of the product manufacturers – were quoted. Not applicable. It isn’t possible to compare existing alternatives to these products because there is no information documenting efficacy of the products. The widening availability of these products is eminently clear from the story. And the fact that melatonin has not approved by the FDA as a food additive is explained. The relative novelty of these products – and their spread – is clear from the story. It’s clear that the story did NOT rely on a news release. Claim: Dessert, Laid-Back and Legal

SOLUTION:
The story offers good context – starting with a recollection of over-the-counter melatonin claims that were “the rage” among frequent fliers back in the ’90s. And reminding readers that “promoters of these are appealing to people who think it’s better to do things outside of the medical establishment.”  It can be a public service to do this kind of reporting when new fad products are promoted without evidence of safety or effectiveness.