As the comments on the Centers for Medicare & Medicaid Services (CMS) website concerning the coverage of Provenge continue to mount, some people inadvertently, and some deliberately, have submitted inaccurate information. Care To Live (CTL), with the help of two of our exceptional physician and scientist friends, Dr. Robert Rostock and Ocyan respectively, continue to set the record straight.

It remains the opinion of CTL, based on all sources of information and investigation, that the CMS review is not about coverage or non coverage of Provenge. It is about interpreting the label, and how much to require from physicians prior to granting reimbursement approval.

We believe that the CMS review could and should actually lead to more patients being covered rather than less.

The argument should not be about coverage vs. non-coverage it should be about how early in the treatment regime patients will qualify for on label use.

We believe that CMS is wrong in not being more specific in their PR release, as to the specific purposes of review. They themselves are responsible for the circus-like atmosphere they have created. They should immediately issue a clarifying statement on this topic. Again, they have no legal or medical basis to deny coverage.

Dr. Robert Rostock, a first-rate prostate cancer Radiation Oncologist, who is in the trenches as he fights each day to treat men with late stage prostate cancer, provided his expert opinion.

“The label does need to be clarified. The sad truth is that most patients are diagnosed with a bone scan when there is already significant pain. That is the reason for the bone scan in the first place in most cases.

“Progression to hormone refractory disease is usually made by PSA measurement. A bone scan may not be done until the patient is symptomatic depending on the doctors discretion.

“Waiting for symptoms may make a patient ineligible for Provenge if they have severe pain.

“Therefore, I feel that the label should be hormone refractory, period, whether or not there are actual bone mets on bone scan.

“This allows for earlier treatment and prevents people from falling through the cracks by progressing to a painful state in situations where they have PSA progression but no bone scan performed until they develop moderate to severe pain.”

Ocyan, a brilliant scientist, and Doctor Rostock are in agreement. Ocyan helps explain the misnomer, the ‘mean’ versus the ‘median’, concerning misinformation in some of the comments that the survival advantage is only 4 months.

“The key part of the poster’s thesis is wrong. He made the classical mistake of confusing “the median difference”, i.e., the difference between two medians with “the median” itself. It is true that the median is the data point at which there are an equal number on the left of it as there are on the right. However, the life time distribution of patients on the left of the median is very different from those on the right. On the plot of a survival curve, one can see that points on the left of the median are bunched together because they all died before the relatively short median. However, on the right (also often called the tail of the survival curve), they can spread out to many years.

“The spreading patterns of the tails of the survival curves for a treated population and an untreated population have a huge impact on “the relative ratio” of survived patients on both populations from year to year. This is why we sometimes say the median difference really does not tell the tale of the tails.

“To make that concrete, let’s assume an exponential survival probability function and see the ratios of the survival rates on two arms of a trial from year to year assuming some fixed medians. First, note that this is a very conservative assumption for patients in the Provenge trials because we know that the hazard ratio was improving with time instead of staying static if they were exponential. That means that we will underestimate the survival ratios as seen in the Provenge trials!

“Without further ado, let the treated median be  25.8 months and the placebo median be 24.7 months as in the IMPACT trial. The survival rates from year to year for the first 10 years will be:

1: T=0.72 P=0.68 T/P=1.06
2: T=0.52 P=0.46 T/P=1.13
3: T=0.38 P=0.32 T/P=1.20
4: T=0.28 P=0.22 T/P=1.28
5: T=0.20 P=0.15 T/P=1.36
6: T=0.14 P=0.10 T/P=1.44
7: T=0.10 P=0.07 T/P=1.53
8: T=0.08 P=0.05 T/P=1.63
9: T=0.05 P=0.03 T/P=1.73
10: T=0.04 P=0.02 T/P=1.84

“That is, on the first year, about 72% of treated patients live while only 68% of untreated patients live. The ratio T/P would be 1.06 (or .72 divided by .68). But as time progresses, the relative difference between the two populations widens such that by year 10, the ratio T/P becomes 1.84. That is there are nearly two to one treated patients surviving 10 years than placebo patients.

“The above example is very conservative when compared to the Provenge trials. In fact, in the integrated data of D9901+D9902a where ALL patients were followed out to three years, the two to one ratio was seen at 3 years. The IMPACT trial had too many censored patients for the estimate at 3 years to be reliable. But even so, the Kaplan-Meier estimate of the ratio at three years was 1.38, or the equivalent of somewhere between 5 and 6 years in the above table.

“The bottom line is that as time goes on, the number of treated patients who survive will far surpass the number of patients who were not treated. That is the definition of efficacy for a drug. And, it is clear that Provenge will save many lives!

“The focus on arcane statistics is wrong with respect to commenting on the CMS NCA inquiry. CMS will not overturn the FDA finding of efficacy no matter how much false information is thrown at it. The data is unequivocal that Provenge is an effective treatment, in fact, far more effective than the previous standard of care, Taxotere, and without most of its debilitating side effects.

“CMS will allow Provenge for on-label treatment but what they need to do is to verify clearly what that means. Certain hormone-refractory prostate cancer cases that are asymptomatic or minimal pain still do not fit the acceptance criteria because their scans do not yet show bone lesions or tumors. However, within a very short span of time, such patients will develop lesions and tumors.

“Not allowing immediate treatment when they come hormone-refractory would increase the chance that new tumors can happen in vital organs and dramatically reduce the survival chance of those patients.

“It is my opinion, CMS should clarify that such patients be allowed immediate treatment with Provenge without any waiting time. The focus of the CMS action should be this because ultimately it will save Medicare money when such patients can avoid expensive intensive care if their disease goes to the wrong places.”

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Tags: Breast Cancer, Care To Live, CareToLive, CMS, CTL, Dendreon, Dr. Robert Rostock, FDA, Immunotherapy, prostate, Prostate Cancer, provenge

This entry was posted on Sunday, July 25th, 2010 at 8:21 am and is filed under The Cause, The Dysfunctional FDA. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.