PREFACE

The premise of my claim for standing before the Court is my unique position as father of the plaintiff and the insights I gained in studying the case from day one. During these studies, my viewpoint broadened from just seeing justice provided my daughter to include recognition that the Court has the opportunity to improve the drug approval system significantly.

The exploration presented here includes short summaries of the development of the drug, the medical procedure that led to the filing of Levine vs. Wyeth, and a revised drug approval process illustrating the improvements. Two of the summaries are presented in narrative form.

There are a few hearsay statements in the descriptions. They don’t attempt to enter new evidence; they only describe how information was received. The submission also contains statements that may not meet the full requirements for classification as common law, but this Friend believes they are logical and common sense.

THE DRUG AND ITS APPROVAL

Wyeth has three versions of the medicine that avoid risk by insulating the drug from arterial corridors. These are a suppository capsule, an oral pill, and a liquid to be injected into the fleshy part of the rump. The dangerous version of the drug used in treating Levine was a convenience form for those care givers routinely using intravenous injection.

The FDA and Wyeth used the standard procedure: the drug company develops the drug and determines its efficacy. The dangers involved in using the drug are carefully identified and warning labels outlining actions health servers must take to avoid dangers are developed and included with the medicine. The FDA monitors this effort and the drug is not approved until both the FDA and Wyeth agree. If any problems are discovered, corrections to the process or the warnings are made.

Many drugs are dangerous. The drug involved in Levine vs. Wyeth is extremely so. To insure that this drug does not cause the loss of limbs and even life, a complex series of steps must be performed perfectly. (1) The liquid medicine must be examined for cloudiness or change in color (damage by light); (2) The drug needs to be diluted to a specified concentration; (3) The proper dosage must be prepared; (4) the rate of flow of the diluted drug must be kept below a defined maximum; (5) The intravenous patch in the wrist must be precisely positioned and inserted; (6) The IV must be proven to be flowing properly; and (7) Drug flow must be stopped immediately if the patient complains of intense pain when the flow starts.

Finally, these conditions and the appropriate warnings of the consequences of failure are recorded in a warning label and included in the drug package.

The process generally works well, but there is no evidence that caregivers have had any part in the approval process. Yet they end up being the carrier of all the risk. Assuming the drug warning label is adequate, they have become the potential “intervening causes” protecting the drug manufacturer from liability. It doesn’t seem quite fair.

At time of treatment of Levine, there was a history of serious maltreatments and the FDA and Wyeth were involved in refining the labeling. Wyeth had proposed a change that the FDA had not approved. There was recognition that the warning label is inadequate, but there was gridlock.

It is at this point that Wyeth took an action negligent almost to the point of grossness. Its action was to take no action. It was tragic and it placed Wyeth at the center of liability.

The proper legal and ethical action was to announce to all users that the medicine was temporarily withdrawn until new and adequate warning labels had been issued and to reopen discussions with the FDA to complete the work.

Instead, Wyeth decided to wait until maltreatment and lawsuit occurred, preferably one like Levine’s where no intervener’s failures have been shown to have occurred. This then would provide opportunity to seek clarification of the FDA/drug company liability (to change the law to shift the ultimate liability to the FDA).

This Friend of the Court vividly remembers a family review session with Levine’s lawyer during which I commented “the only thing that explains Wyeth’s behavior to this point in the trial is that they seek ultimately to change the law”.

LEVINE’S TREATMENT

The stage is set for the system to take care of Diana Levine. She is in a health Center bed, fighting an extremely painful migraine, her life-long nemesis. She has an IV in her wrist and it has just been used successfully to inject a strong pain killer and sedative. The Wyeth medicine has been prepared and mounted following the procedure outlined in the drug label literature. The care givers hear no complaint of pain as the flow begins.

In less than an hour every capillary in her hand below the IV had closed, dooming the limb. Valiant efforts were made to try to save the hand. Blood thinners so strong that she bled through her skin were injected. She endured weeks of pain as her doctor tried to head off the need for amputation. Finally, gangrene forced two surgeries to remove of her hand and significant portion of the lower right arm.

The state lawsuit against Wyeth is filed and follows a path the reverse of the treatment. First, it was proven that the Wyeth drug was properly prepared and inserted in a functioning IV in full compliance with the label instructions. This determined that the warning label failed to define a path that would prevent injury. Then damages were calculated and assessed.

The jury decided unanimously in favor of Diana. It was confirmed throughout the state court system. Wyeth initiates the subject Federal appeal to the US Supreme court, claiming it was helpless to change the labeling without FDA approval, which had not been granted.

AN IMPROVED PROCESS

This Friend recommends strongly the court go beyond the current label-changing difficulties and examine the initial process that led to the inadequate label. The easiest way to describe the actions that could have produced a satisfactory procedure and label is to consider how the process might have been better. Such a process is described here in narrative form.

First, the FDA doesn’t wait for the drug company to develop the drug handling procedure and propose a label. The FDA, with its special concern for safety review, takes an active role in the procedure from the beginning. Both the FDA and the drug company are fully aware that this drug is very dangerous. Representatives of care-givers of different levels of ability to care are enlisted in the team.

In the initial conversation, when the drug company suggests the care giver should check for light damage to the liquid and dilute the standard concentration to a safe level. The alert FDA examiner says, “Why do we want to take a chance that the checking and dilution may be botched by some nurse? Why don’t you reduce this risk to zero by shipping properly automatically diluted and checked medicine in a ready-to-use condition? The risk for these steps is eliminated. The drug company says “OK, and thanks for the suggestion!”

Drug company: “Next, the drug dosage must be correct and it must be fed at a very low rate. We will specify the rate that must not be exceeded.”

FDA: “Why don’t you deliver the drug as individual opaque dosages instead of bulk? This would essentially eliminate the risks of degraded medicine, concentration, and dosage. The preparation will be accomplished by automated equipment under full quality control at the drug factory”.

Drug Company: “Although the cost of the small packaging and automatic dosage and filling is significant, we agree the elimination of risk would more that justify the investment. As I think about it, I believe we may be able to form the treatment package so that it could control the feed rate, eliminating another significant risk. The drug container could just be hung at the top of the IV line. No care-giver adjustment would be needed. We will examine this possibility”.

Care Giver: “There is another problem with the procedure. We are told to stop treatment immediately if the patient complains of pain. However, the administration of the medicine begins after we have injected a heavy dose of pain killer/sedative. Such pain relief is first priority. It is likely the patient is ‘feeling no pain’. What is needed is a small, safe test kit able to test the intravenous tap quickly. Then we could do a quick proactive test before the painkiller is injected. We would get the patient’s attention and instruct the patient to report any pain at the beginning of the test and before administration of the pain killer or full drug injection”.

Drug company: “It could be done. It is possible it could be incorporated into the capsule, with one end containing the test mechanism and the other providing the medicine feed at the appropriate rate”.

NOTE:

During his initial study of the drug warning label, this Friend of the Court followed a similar pattern of thinking. He then put the conclusions to work by ordering medical glass tubing. Using a small torch, he constructed a sample drug delivery package. It worked fine!

The above narrative demonstrates that a much lower risk process with a very simple label could have been developed with the FDA, Wyeth, and caregiver representatives concentrating on eliminating risks rather than passing the high risks downstream and depending on labeling to prevent the tragic drug failure. In this Friend’s opinion, this was one of Wyeth’s and the FDA’s failures: not concentrating first on reducing risk.

INTRAVENUS INJECTION

This Friend believes the re-oriented team should hold one more discussion, one devoted to the risk of intravenous injection of dangerous drugs. Here is the final discussion.

FDA: “Let’s stop looking at the details and discuss the inherent risks of injecting any dangerous drug intravenously. We all know the needle is injected in a tiny passageway called the carpo tunnel. The channel houses a whole family of tendons, arteries, veins, and nerves. It is packed so tightly that a significant percentage of the population requires surgery to expand the tunnel to avoid loss of the use of the hands. The idea of penetrating this area with a very sharp needle to inject a dangerous medicine doesn’t seem to be a wise practice. Even if the initial insertion is successful, it seems quite possible subsequent motion would cause failure during injection of the medicine.

It seems to me that the only satisfactory warning label would say ‘Don’t inject this medicine intravenously.’ I recommend this version of the medicine not be approved and that we stick with the other forms proven to be safe”.

Other team members, including the drug supplier: nods of agreement.

If this decision had been made and promulgated, all other “generic” producers would have been bound by it.

STATE COURT JURIDICTION

Some have argued that jurisdiction of medical malpractice cases should be moved to the Federal Courts. This Friend believes this would be a tragic move for two important reasons. First, this would place an impossible burden on the Federal Court system. The state courts now are carrying the heavy burdens. Second and more important, States are different and require different practices.

An example of the latter point is the comparison of Vermont and New Hampshire. The emergency medical facility available to Levine in the north central part of Vermont is a local (5 miles) medical clinic that is manned by a Physician’s Assistant during the night. The hospital to which Levine was transferred for sophisticated treatment is right across the river at Lebanon, New Hampshire (about 60 miles southeast). She was moved there from the Montpelier Hospital where adequate care was found to be unavailable.

Dartmouth Hospital is a remarkably competent treatment center. For example, three specialists are assigned full time to circulate throughout the hospital to monitor the condition of intravenous patches, changing them out when they are faulty. Three others are similarly assigned to examine the psychological condition of patients. Clearly it is the responsibility of drug companies to be aware of these differences between care facilities and adapt their practices to serve the full range of caregiver abilities.

The State Courts help to insure this is done. To destroy these services in favor of Federal jurisdiction could be catastrophic.

CONCLUSION

A State of Vermont jury decided, by unanimous agreement, that Levine’s care-giver faithfully followed the procedures described in Wyeth’s warning label. It judged that the label was inadequate to avoid the loss of Levine’s hand. It awarded damages. The decision was validated by the state appellate and supreme courts.

Some truths are self-evident: no one had the right to sacrifice Levine’s right hand in order to test the proposal that the decision of a bureaucrat in Washington could relieve a drug company of liability for the damage done by its medicine. This is exactly what Wyeth has done.

The time has come for the Court to provide justice, justice already delayed for seven years. It can do this simply by confirming the State Court’s actions in the Levine vs Wyeth case. It should do so immediately and not wait to review other somewhat similar cases selected for review.

However, the court should not lose the opportunity to improve the drug approval process greatly by exhorting the FDA to include care-givers in its review team and to remind all participants that the principal objective of the review is to eliminate or minimize risk and not just arrange for distribution of liabilities.

THANKS

It is hard to describe adequately the thanks that this Friend of the Court owes to the Court for allowing this somewhat unusual Friend’s statement to be examined and considered.

Dr. Oliver H. Winn
422 Heliotrope Avenue
Corona Del Mar, CA 92625
owinn@worldnet.att.net
949 675 4016

Not a girl thing at all!! Have to be a New Jerseyan to understand, its an inside political thing.

Failure to Warn,..Lets use Pfizer as an example, shall we. In 1983, before zoloft was approved, a 44 year old man was removed from a clinical trial due to thoughts of killing others, and then himself, Clinical Investigater stated that this episode was due to Study Drug!!. Pfizer reported the AE to the FDA that the gentleman was removed from the clinical trial due to Nausea. In this case pfizer didnt tell FDA the whole truth. Ten years later to the day,..Pfizer draws up the “INFAMOUS PROSECUTORS MANUAL”. BTW,…FDA is a Joke..

I think if you look at the data, HCP mistakes kill more patients than drugs. Not even talking about docs writing for meds they shouldn’t. Why every hospital in the country is not barcoded is AMAZING to me. Look at the whold Quaid incident - a hospital too cheap to barcode, kills 3 kids and the manufacturer gets sued?!?! So we can talk about drugs because they are the easy “big target”. What about your local hospital that has been making millions for years in your backyard without doing everything possible to improve patient outcomes? I know, not as easy or popular as blaming big drug companies. But believe it or not, hospitals do all they can to make money as well. They are run by an administrator, not a HCP. I would argue that pharma actually is looking after pts better than your local health care system.

Here are a few examples of the sort of circumstances in which I do think accountability out to figure in:

1. A company knowingly and deliberately does not report deaths from acute liver failure to FDA (later saying: this was because they occurred abroad and they “didn’t know” they had to report these). See the Oraflex case during the 80s.

2. A company (or the person responsible therein) counts acute liver failures in such a way as to reduce them by one-third in reporting the number to FDA. The FDA has no way of knowing that happened (until it later comes out in court). That’s one version of Rezulin story.

3. A company suppresses its internal studies of AE rates of their drug relative to others in its class; or - although concerned about the differences - decides not to pursue a study that has been recommended by some inside that company. One version of the Baycol story, and several others.

4. A company directly denies AEs it knows of, shreds records, hires KOLs to give “testimony” in favor of drug, tries to intimidate or bribe (with cash) those who see it otherwise (even at FDA) - thalidomide most obviously, and a number of others too.

5. A company puruses what Jerry Avorn of Harvard calls “passive-aggressive” compliance - data is chronically submitted late; Medwatch reports are “headlined” in ways to disguise or camoflage all that the company knows is going on (requiring FDA’s ODS to find needle in haystack), etc. One version of fen-phen story and several others.

You and I both know examples of this sort could make a very long list. They have nothing to do with scientific disagreement or risk-benefit equations.