The release focuses on a recent paper published online in Cell Transplantation. According to the release, the paper reports that a clinical study found the use of CD34+ cells reduced the frequency of “refractory angina” — chronic chest pain caused by reduced blood flow to the heart. However, the release does not quantify benefits, address potential risks, discuss costs, discuss how this compares to alternative treatments, or explain the research in language that would be accessible to non-expert audiences.
We were confused about where the release originated because the source of the release, the “Cell Transplantation Center of Excellence for Aging and Brain Repair,” is misleading. A journal editor explained that Cell Transportation journal is co-housed with the Center of Excellence for Aging and Brain Repair, part of the University of South Florida. But the research wasn’t conducted by USF.
[Editor’s Note: The release states that an “unedited” version of the study is available at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1584_Henry_et_al. A study co-author confirmed that the link above is to the final version of the trial results.]
A 2012 paper on refractory angina noted that approximately 1 million people in the U.S. are thought to suffer from the condition, which can have a significant impact on quality of life. It is, in short, a fairly common condition and — for that reason alone — it is worth writing about emerging treatment options. However, it is important to place such emerging treatment options in context. How promising are they? How far removed are they from clinical application? Do they pose risks? These are fundamental questions, and this release does not address them in a meaningful way. The release also uses language incomprehensible to the lay audience and does not define many of the key concepts.
The release does not discuss costs at all. Given that this was a phase II study, meaning it is still at least one step removed from clinical use, we don’t necessarily expect a release to give a precise cost to the treatment. However, we do expect cost to be addressed in at least some capacity. For example, is there an expectation that this treatment would be comparable in cost to other treatment options for angina? Given that this was industry-funded study, the release could have addressed this in at least broad terms.
As the release appears to be comparing this procedure to bypass surgery, it would be helpful to know exactly what is involved in obtaining “autologous” (self donated) cells and “intramyocardial delivery into the ischemic zone” later referred to as “injected.” It is unclear if this is a surgical procedure, inpatient hospital treatment or clinic visit, all of which would influence the final cost.
The release does not quantify benefits at all. The headline tells readers that the treatment “reduced angina frequency.” The body of the release notes that there was “a significant reduction in angina frequency” and that “significant improvement in both angina frequency and exercise at 12 months and a trend toward decreasing major cardiac events.” However, there are no numbers here. How much improvement was there? How much less frequent were episodes of angina in patients who received the treatment relative to patients who received a placebo? The release doesn’t tell us. The release also says there was some effect at 6 months for the placebo group that dropped off over time, but how much and what was the benefit compared to the group that received treatment?
The release does not address potential risks associated with CD34+ treatment. The Cell Transplantation paper did not report significant adverse effects associated with the treatment, but noted that “the longer-term effects of this treatment are unknown.” Even if there are no additional risks associated with a treatment, a release needs to tell readers that — and, in this case, the researchers themselves make clear that they do not yet have a clear assessment of potential risks.
The release describes the study succinctly, stating that the study was “a two-year, phase II, randomized, double-blind, placebo-controlled clinical trial” of 167 patients. That’s good. But it’s important to explain to readers what phase II study is — namely, a study of an experimental drug or treatment designed to determine if the treatment is effective and to evaluate its safety. The release doesn’t tell us much about the study participants, other than that they had been diagnosed with “class III-IV refractory angina.” Were the patients men? Women? Old? Young? Those details are relevant. Similarly, the release doesn’t tell readers what “class III-IV refractory angina” is. Perhaps more importantly, the release doesn’t tell readers that the initial clinical trial was completed in 2009 and was, according to federal clinical trials data, designed to “evaluate the efficacy and safety of intramyocardial injections of adult stem cells in patients with refractory chronic myocardial ischemia.” Later, the researchers launched a follow-up study focused on quality-of-life impacts related to the treatment. Myocardial ischemia, as the Mayo Clinic explains, “occurs when blood flow to your heart is reduced, preventing it from receiving enough oxygen.” It can damage the heart and contribute to heart attack or irregular heartbeat. Angina is a symptom of myocardial ischemia, not a causal factor. Since the study was originally designed to address how effective CD34+ treatment was against myocardial ischemia, it’s worth mentioning that this paper focuses on the treatment’s effect only against a symptom.
The release never defines or describes angina at all. The release treats angina like a disease, rather than as a symptom of underlying health problems. That’s problematic. We do not want to downplay the condition in any way, but it is important to distinguish between symptoms (such as significant chest pain) and underlying causes (such as reduced blood flow to the heart).
The release does not mention funding sources or address potential conflicts of interest. For example, as the relevant journal article notes: “Baxter Healthcare sponsored the study and was responsible for the conduct of the investigation.” At least two study co-authors were former Baxter employees. Another author is listed in the paper as being an employee of Caladrius Biosciences, but a cursory search finds that he was previously a vice president at Baxter. Yet another author has received an honoraria from Baxter, and another has received research funding from Baxter. The paper was not as transparent about these conflicts of interest as it should have been, and the release fails to address them at all. In addition, the release appears to have been issued by the “Cell Transplantation Center of Excellence for Aging and Brain Repair.” Given that the researcher cited in the release is based at the Cedars-Sinai Heart Institute, one could assume that the center is located there. But that would be wrong. There is no center by that name. Instead it appears to be a hybrid of the journal name and the name of the center where it is housed. This is confusing (at best) and misleading (at worst), since the center had nothing to do with the research. Frankly, this is very confusing for readers.
In order to fully appreciate any new or emerging treatment, it’s important to compare it to existing techniques that address the same problem. The release does mention “conventional medical treatments” and “revascularization” but doesn’t explain what those things are nor does it offer any comparisons with this developing therapy. There are a host of other treatments out there, from surgical interventions to pharmaceutical treatments.
The release notes that this paper stemmed from a phase II clinical trial. It didn’t tell readers how long ago the trial took place, or what the treatment’s prospects are (even in general terms) for potential clinical use. In 2012, Baxter issued a news release announcing plans to launch a phase III trial for CD34+ treatment to ” increase exercise capacity in patients with chronic myocardial ischemia.” That trial appears to be related to this research, although that’s not entirely clear. Is it related? And, if so, has that trial moved forward?
As we noted under “Compare Alternatives,” there are a host of other angina treatments out there. Because they aren’t addressed, it’s not clear what makes this treatment novel. The release tells readers that some “patients with advanced coronary artery disease…frequently have symptoms after having had standard therapies and are left with limited treatment options.” The release also states that CD34+ treatment “is an attractive treatment option” for these patients. But it doesn’t tell readers why. Nor does it mention how CD34+ differs from the other “limited treatment options.”
The release also does not establish what makes CD34+ cells attractive as a treatment. It says “because recent studies pointed to the importance of CD34+ cell content in the bone marrow of patients with risk factors for coronary artery disease.” Risk factors do not mean the person will get the disease, nor is there a clear connection between bone marrow and the heart here.
This is satisfactory, but barely. The release headline tells readers that this treatment reduces angina frequency for “no option” patients. But it doesn’t clearly describe the treatment, the condition or the extent to which frequency is reduced — and it’s a little unclear as to why these are “no option” patients. The body of the release says that some patients have “limited” options, but not that they have no options. And it doesn’t articulate what those limited options might be. However, the last sentence of the release provides some needed clarity: “The researchers concluded that for ‘no option’ patients with class III/IV angina refractory that was unresponsive to conventional medical therapy and who were not candidates for revascularization, injection of CD34+ cells resulted in persistent improvement in angina at two years post-treatment.”