Trying to Understand the NCGS/Genentech anti-HER2 Lottery

Here is the letter from NCGS & Associates, as annotated by me in a reply to them.

Dear Ms. Boyce:

Thank you for the plain text version of your statement.

You apparently didn't notice the remainder of my request. Would you please provide documentation, along with your statement, concerning whatever matters are in it? For example, would you provide a copy of the documents reflecting the assumptions put into the lottery model and the changes that have been made from time to time in those assumptions since the beginning of the lottery?

To aid you in providing this documentation, I will list some particular points in a copy of your message, below.

Thank you very much,

John E. Bonine

On Sat, 25 Jan 1997 ncgs_is@awod.com wrote:

NCGS:Dear Mr. Bonine- Due to the previous miscommunication of inaccurate details via telephone conversation with an NCGS employee, I am supplying you with accurate facts regarding the HER2 lottery system. For the sake of the breast cancer patients who may have been mislead by your article, "Annette Friedman's Life Depends on a Flawed Lottery", I ask you to post the following clarification at the source(s) of your original article. If you would kindly provide me with the address(es) where I could locate this clarification once posted, I would greatly appreciate it.

Expanded Access Clinical Trial for the HER2 Monoclonal Antibody

Drug lottery systems have become increasingly used by pharmaceutical companies in an effort to equitably distribute limited supplies of experimental drugs. One such lottery system is being used currently by Genentech, Inc. in an expanded access clinical trial. This trial utilizes the HER2 monoclonal antibody, a potential treatment for breast cancer, which is currently being evaluated in controlled safety and efficacy trials. NCGS and Associates, Inc., the firm that designed and is running the lottery for this Genentech, Inc., trial would like to offer clarification of the lottery design and implementation.

John Bonine phoned NCGS and Associates, Inc. At the time of his call, Mr. Bonine requested technical information about the design of the lottery system. Unfortunately, incorrect information was provided by an NCGS employee who responded to his call. Thus, information presented by Mr. Bonine over the Internet is not accurate in two important ways.

All Available Product is Allocated

First, all available product is allocated. Taking into consideration all possible volumes of demand, NCGS designed the lottery system to distribute all available study drug. With this lottery system, no study drug goes unused. The lottery system is designed to randomize a total of one hundred patients a year at intervals of twenty-five per quarter. During 1996, all slots were assigned.

Bonine:Please provide me with documentation showing that all available product is allocated, the way in which the lottery system was designed to distribute all available study drug, that no study drug goes unused, and that during 1996 all slots were assigned. Please provide me specifically with information showing the method of assignment actually used.

NCGS:Genentech, after consulting with breast cancer advocate groups, worked with NCGS to develop a lottery system that was fair and unbiased and as easy for patients to use as possible. Patients are told immediately whether they will receive study drug or be carried over in the lottery process. They do not have to enter their name in a pool and wait for a designated "draw date" to find out whether they will receive study drug. Additionally, patients are not removed from the lottery process if the study drug is not assigned to them initially. NCGS works with the clinical sites to ensure that patients are notified that they are eligible to be re-enrolled in the lottery. Also, patients can re-enroll every thirty days rather than every quarter.

No Adjustments are Made at the End of a Quarter

Second, no adjustments are made at the end of a quarter. The system does not "adjust" or "think" on a daily basis, and no measures are taken to weight the lottery system at the end of any quarter.

Bonine:Please provide me with documentation showing that no adjustments are made at the end of a quarter, no adjustments are made on a daily basis, that no measures are taken to weight the lottery system at the end of any quarter, and that show just when and how adjustments ARE made. As you are probably aware, a Genentech spokesperson has made statements regarding adjustments that are somewhat more complete than this statement of yours.

NCGS:All possible efforts have been taken by Genentech and NCGS to ensure that the study is conducted with the utmost fairness to all patients involved. No exceptions are made in the conduct of the lottery. And because no exceptions are made, breast cancer patients can be assured that patients are chosen by chance only, not because of any kind of special consideration or outside influence.

Bonine:Please provide documents showing that no exceptions are made in the conduct of the lottery and how, rather amazingly, exactly 25 slots have been allocated in each of 4 quarters, when the slots are supposedly assigned purely on a random basis. As you and I know, a randomization program uses assumptions. It would be remarkable indeed if human behavior, with all its variability, was predicted so well by your program designers that its assumptions on the numbers who would apply each quarter precisely matched the reality of how many DID apply each quarter and, furthermore, despite the fact that normally a randomization process produces results with one or two standard deviations of expectation, yours just happened, four quarters in a row to provide results of exactly 25 per quarter -- with no adjustments or exceptions.

NCGS:Finally, as yet the HER2 antibody is an unproven therapy. Discussions surrounding this therapy should not presume that it is a safe and effective product. Until the clinical trials are concluded and sufficient data are collected, no pharmaceutical drug may be assumed safe and effective.

Bonine:Thank you in advance very much for your anticipated documentation.

Sincerely,

John E. Bonine

NCGS's further reply is provided on an additional page, again in the form of my annotated reply to them, which includes information from the Informed Consent form.

Mail message to:John E. Bonine