Friday, January 13, 2012

Dr. Turkel's Book, Part 5: The Ruin of the U-Series By The FDA

Well, I know it's been much longer than I had wanted to get this 5th part of Dr. Turkel's book up. But, blogging has been slow the last few weeks.

You can see the first 4 parts covering his book at these links: Part 1, Part 2, Part 3, & Part 4.

As I mentioned in Part 4, even though Dr. Turkel had amazing success and great results with his U-Series, there was massive unacceptance by the "big wigs"....doctors, associations, the NIH, and even the FDA. But ultimately the FDA would cause the most damage to his U-Series.

Dr. Turkel started applying for New Drug Approval from the FDA in 1959. It was the start of many years of a saga. It ended with parents not being able to receive the U-Series from their doctors and eventually closing Dr. Turkel off to only supplying patients in Michigan with the U-Series.

There are two chapters that cover this full saga in Dr. Turkel's book. I will attempt to give a general overview, but it is quite involved.

The first requirement was that he have a clinical study for his U-Series. That's fair enough, but then the doctors who were supposed to be conducting this study, changed what the children in the study were receiving and were not giving them the full U-Series. They also did not cooperate with Dr. Turkel's approach, therefore causing more problems. There were many other problems with the conduction of the study and it was also terminated before it was supposed to end.

Instead of just a clinical study (which was attempted, but had problems, as mentioned above), the requirement then turned to needing to have the study be a double-blind clinical trial. Dr. Turkel argued that there was too much variance in individuals with DS to accurately do a double blind study. But, eventually he agreed to let it be done. There are many potential problems with a double blind clinical trial and Dr. Turkel's book discusses this.

Dr. Turkel attempted to comply with FDA regulations for 25 years without success.

In 1959 when Dr. Turkel went to the FDA to request the New Drug Approval, Trisomy 21 had just been discovered as being the cause of DS. But, many did not know the full implications that the extra genes and proteins caused on the triplicated chromosome. Because of this, the FDA did not consider the potential causes that could be caused by them. As Dr. Turkel's book states,

They [the FDA] dismissed the argument that the extra genes explained the presence of accumulations that the "U" Series was designed to reduce. They mistakenly concluded that since he "U" Series could not remove the chromosome, it could not help the patients.
 Some may wonder why Dr. Turkel attempted to get approval from the FDA. This is why,
Dr. Turkel admits that he was a novice in politics. He believed that if a physician developed an efficacious treatment for a devastating and previously untreatable disease, that the Federal agency charged with consumer protection and health would provide assistance. Former FDA Commissioner Edwards likewise stated that the agency existed to promote the approval of beneficial products. It was obvious to Dr. Turkel that the "U" Series was beneficial. The actions of the FDA bewildered him.
 Some of the roadblocks Dr. Turkel ran into from the beginning are as follows,

On page 210 of his book, it states
Between 1959 and 1962, the FDA failed to advise Dr. Turkel how to comply with the existing requirements. The FDA did inform him that a drug company had to be the sponsor of the IND and NDA. To comply, Ubiotica Corporation was formed to sponsor the "U" Series.
In 1962 the FDA created a new guideline for getting drug approval and that is where the "proof of efficiacy" (the clinical studies which he was told to do) come in. 

But, it wasn't until 1963, that Dr. Turkel was advised on what to do next by his attorney. He was advised to file an Investigational New Drug (IND) and New Drug Application (NDA). This is what happened after he did that,
November 26, 1963, FDA Commissioner Larrick sent Dr. Turkel a telegram and letter informing him that the IND had been withdrawn and, furthermore, that the "U" Series "should" be withdrawn from investigators, and that treatment of human beings "should" be discontinued.
Dr. Turkel, being a novice in politics and the workings of the FDA, took the above letter as saying that he had to stop treatment with the "U" Series. So, for 6 months he did not use it until there was a  meeting with a Senator to address the use of the "U" Series with a particular patient.

Once the IND was withdrawn, Dr. Turkel attempted to comply with the new regulations put into place in 1962. Yet, there were some problems with the cost, as is written on page 211,

He did not know that they were so "stringent" that it cost millions of dollars for new drug approval (the average cost in 1984 was $87 million over a period of seven to ten years).
Dr. Turkel went ahead to try to conduct animal studies in an FDA approved laboratory. Yet, he had some concerns.
Dr. Turkel expressed concern. He asked his attorney whether, having set up the protocol and approved it, the FDA might then later consider it inadequate. The legal opinion was "in the even such [studies and] amendments are accepted as suggested by the FDA, we do not contemplate that at any later date the FDA will take a position that said tests are insufficient for the purposes designated . . ."
...As it turned out, Dr. Turkel's forebodings were more accurate than the legal assurances.
The book states on pages 213-214,

Regardless of the outcome of the studies, the FDA seemed unwilling to approve the "U" Series:
"We think it will be difficult for Dr. Turkel to prepare a rational plan for the further distribution of the drug for investigational use." (Smart, 1/23/63)
"There is no basis for considering that the random, empirical and scientifically irrational choice of drugs and dosages contained in this NDA is either safe or effective in the management of Mongolism. It is our opinion that it may be impossible to write suitable labeling for efficacy for this product: in view of the cytogenetic basis of mongolism, we recommend that you abandon work on this application. " (Lockhart, 8/2/63)
"It is extremely unlikely that this product will ever meet the stringent requirements of the Food, Drug and Cosmetic Act, as amended." (Hodges, 12/12/66)
Common sense dictates that medication for the treatment of a serious disease should be not withheld solely for the above-cited reasons.
Unfortunately, common sense isn't so common. And Dr. Turkel would continue to find out the FDA had a serious resistance to his U Series, yet he wouldn't ever find out the exact reasons as to why they would not approve it, as is written on page 215,
...No reason has been given for the FDA's failure to assist a physician who sponsored a new drug,...
 Dr. Turkel eventually requested a hearing with the FDA as to why they would not allow approval of the "U" Series and his hearing eventually went all the way to the Supreme Court. The final ruling was by the Sixth Circuit Court and it was found the the "U" Series had no basis for use, because it could not remove the extra chromosome.

Dr. Turkel even attempted to get more recognition by the FDA by working in foreign countries and prescribing the "U" Series in Switzerland (many European countries were successfully using and approving the "U" Series for years). But, it was still to no avail.

Finally the FDA limited Dr. Turkel's shipment of the "U" Series between the states and allowed him only to use it with patients in Michigan...even though it was not regulated by the FDA, because they had never allowed approval of it.

It's a sad situation that Dr. Turkel ended up in. It's a shame and disgrace that an agency in the US has the ability to deny potentially helpful treatments to people with Down Syndrome.

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