Exhibit C Comparison Of Side Effects Assessment
By Life Raft Group As Compared To That Of Novartis
Using the latest side effect data published by Novartis in a memorandum to pharmacists dated August, 2001, we compared the frequency of reported side effects to Gleevec by the Life Raft Group to those reported by Novartis. The Novartis data refers only to patients using Gleevec for Chronic Myelogenous Leukemia. The Life Raft Group data refers only to patients using Gleevec for GIST.
For most side effects, the data is fairly similar, with the Life Raft Group reporting a higher amount of fatigue, diarrhea and skin problems, and the Novartis Group reporting a higher amount of edema, nausea and cramping. Reported reflux was about the same. Only one side effect, namely eye puffiness, was reported by the Life Raft Group and not by Novartis, although that might be explained by a different method of categorization. (See Chart 6).
Where there are significant differences is in the reporting of the severity of side effects, with the Life Raft Group tending to define a greater number of side effects as severe.
There are two major reasons for these differences.
The first is that Novartis, like all clinical researchers, uses the toxicity standards established by the NCI (National Cancer Institute), whereas the Life Raft Group uses its own patient severity rating scale.
The second is that Novartis, like all clinical researchers, derives its data from the reports of on line clinicians, whereas the Life Raft Group derives its data directly from the patient. This raises the issues of whether the on line clinician correctly hears, interprets and records what the patient says and whether the patient chooses to accurately report their side effects to this person. It also raises the issue of whether the Life Raft Group volunteer who records this information correctly hears, interprets and records what the patient says and whether the patient chooses to accurately report their side effects to this person.
Although we have no Novartis data on GIST-Gleevec severity, we do have the reports of the clinical researchers at the May, 2001 ASCO (American Society of Clinical Oncologists) Conference. As is the case with all clinical trials, the GIST-Gleevec trial researchers used the NCI toxicity standards, with grades 3 and 4 events being reported by the U.S. trials and grades 2, 3, and 4 being reported by the European trials. Let’s compare the U.S. report, using grades 3 and 4 to define toxicity, to the Life Raft Group methodology. We will use as an example the fact that a clinical trial patient has diarrhea.
The U.S. ASCO Report notes that, of 145 study participants, there were 0 cases of diarrhea as a grade 3 or 4 toxicity event. The Life Raft Group notes that, of 61 study participants, there were 13 cases of diarrhea reported to be severe.
Let’s take a look at how this difference in reporting could occur.
Assume that a patient had three incidents of diarrhea per week prior to beginning Gleevec.
Assume that patient now has three incidents per day since beginning Gleevec.
Using the current NCI toxicity scale that situation would rate a one, on a scale of 0 to 5, with 0 being none and 5 being death.
Using the Life Raft Group Severity Scale, the patient might conclude that three episodes a day of diarrhea for the indefinite future, might rate a 7, on our scale of 0 to 10, thus qualifying for a ranking of severe. One might ask the NCI analyst who constructed the scale: How would you rate the severity of having to cope with an average of 3 episodes of diarrhea per day for the rest of your life?
Given that about half of those among the Life Raft Group who report severe side effects, report three or more, this poses an interesting dilemma. How do you combine the several different side effects into one quality of life whole? To some extent we have begun trying to do this by looking at functional effects, in addition to rating side effects separately. (See Table 4).
At some later date, we may return to this subject in greater detail. Our purpose today was to point out the different perspectives of a patient group and a clinical trial group in looking at the severity of side effects, and to suggest that both may help understand what a patient is actually going through as they try to live their life.