On Friday, December 20, 1996, I talked to the 800 number for NCGS and Associates, who are running the Genentech, Inc. lottery mentioned in the letter from Genentech's public relations department on why they could not supply their anti-HER2 medication to Annette Friedman. I talked to one of the persons responsible for taking telephone calls about the program.
They answer the phone as "NCGS Expanded-Access Program" or something of that sort.
The most important information is that they have NOT been filling the 25-per-quarter quota during some quarters!!! So something else is going on here.
The woman who answered my questions said NCGS and Associates is a clinical research organization working on various clinical trials. Their role is basically to run the Genentech anti-HER2 lottery (this sentence is my description, not what she said). She said they are "doing pre-screening to ensure that patients are eligible, then they send information to patients, doctors, or family members about it.
"Either a doctor or patient can contact us, or a family member, give their history, and we determine eligibility."
I asked what some of the eligibility criteria are.
"It requires progression after 3 or more chemotoxic regimens, and that the person be HER2 positive."
"This particular study is run on a lottery system."
"Patient is entered into a lottery system, because of limited supply [of the medicine] and because it is complicated to make."
The drug is given by "weekly infusions, and the patient must sign a consent form so that information can be sent to the FDA from the study."
How many patients can receive this?
"There are 25 per quarter slots, which works out to 8/month."
So are they drawn once a quarter, once a month, or what?
"They are filled as the lottery fills them. Anyone can call in."
How many are there competing for the available slots?
"I can't give you a set number who would call in."
"As people call in, they are done." What she meant is explained later.
"We haven't even filled them all. We had trouble making the 25/quarter. Eligibility criteria are quite strict. We haven't had as many calls as we expected."
She explained that a person's name or something is entered into a computer program, and the program does something, and spits back the answer whether the person gets the drug or not.
"The program knows that 25/quarter will be selected; it learns the number assigned and what it needs to assign before the end of the program. If it gets 2/weeks shy of the quarter and all the slots are not filled," it makes adjustments.
I found this confusing, so kept asking questions. I want to know whether the program kept names in its database for some time, or what?
"If you are eligible and don't receive the drug, you are carried over and you may re-enter. The patient is sent a card saying it's been 30 days, please send updated info so we can determine if you are still eligible and we'll reenter your name."
I asked how long it has been going on.
"Has been going on for about a year."
I asked the criteria again.
"Over 18, HER2 overexpressed: 1+, 2+, or 3+ overexpression."
I asked, why didn't they just say everything over 1 counts?
She didn't know.
I asked who determined eligibility.
"Grading is done by the doctors at the site, not by the company. The doctors have the test results to say yes or no. There are serum tests that are done; The doctor sends in lab results, history, etc., and we verify it."
Ah, so the doctor makes a determination, then sends in a name and the data, and you check to make sure it fits?
Correct, she replied. "The whole point of a clinical trial is to determine if it's safe and it works, so no point in entering non-eligibles in it."
What else is on the eligibility criteria?
"Bidimensionally measurable or evaluable disease; willingness to sign the consent form."
"And there is a whole list of 13 exclusion criteria." They'll be in the fax.
I asked said, "So the computer makes the decisions, really?"
Yes, she replied. Genentech has nothing to do with those decisions. That wouldn't be acceptable to the FDA.
"The protocol was approved by the FDA."
I asked if there is a protocol number.
"We are bound by confidentiality not to reveal that."
But some protocol numbers are on the Internet.
I should add that once when I called FDA someone said they could tell me NOTHING about any clinical trials on epirubicin or even whether they are being conducted!
"There are some other HER2 studies -- you are either eligible or not. You either get the drug or a placebo. Besselaar, 1-800-289-1119."
She said she would brief the others in the office, in case I called back, so anyone could answer my further questions.
They have thus far failed to answer my questions about just when and whether and how adjustments are in fact made in the lottery, however.
The Vice President of NCGS sent a carefully prepared statement to me and asked that I post it on my Web site as a correction. I wrote back for clarification before posting. She wrote back without answering my questions for documentation of the matters in the carefully prepared statement. I have decided to post our continuing exchange, so that anyone may judge for her- or himself whether there is anything in the NCGS official statement that convinces you of any errors in the description posted above about how the lottery is "adjusted" from time to time because of variations in enrollment.
I believe that the magnitude and timing of these adjustments can produce substantial unfairness. Variations in expected applications for the lottery are to be expected, as with anything else in human events. I cannot figure out why NCGS and Genentech won't discuss these variations and the methods they use for accounting for them. What's the big secret?
Read the annotated NCGS letter by pressing this link.
John E. Bonine