This is a medical malpractice case in which it is alleged that defendant Shah departed from good and accepted practice by continuing the use of ciprofloxacin (cipro) to treat osteomylitis after the onset of certain symptoms. The plaintiff, then 12 years old, was being treated for a congenital condition known as Crouzon's Syndrome. Shah prescribed cipro to treat the osteomylitis, an infection. It is claimed that the cipro should have been discontinued after complaints of joint pain and that the continued use of cipro after the complaints were made has caused plaintiff to suffer from permanent tendinitis.

Defendants claim that there is no scientific evidence to support plaintiff's claim and requested a Frye hearing to determine whether it is generally accepted in the medical community that cipro can cause permanent tendinitis in children. Both sides submitted scientific articles on the subject, as well as memos and affidavits, and the court determined that a Frye hearing was appropriate. The plaintiff called Charles Stier, a Ph.D. in pharmacology and the defendant called Margaret Hammerschlag, M.D., a pediatrician with a specialty in pediatric infectious diseases.

Stier was retained by the plaintiff to do a search of the medical literature regarding the involvement of fluoroquinolones in causing tendinopathy, a term embracing all tendon problems, not just tendinitis. Prior to be being retained, he had never done any research of his own and had never read any literature on the subject. His only knowledge on the issue was derived from a review he did of articles he found on the PubMed website and articles that were sent to him by plaintiff's counsel, solely for the purpose of testifying in this lawsuit. The opinions which he expressed at the hearing were based solely on this review.

The specific issue presented at the Frye hearing is whether it is generally accepted in the scientific community that cipro, a member of the class of antibiotics known as fluoroquinolones, can cause permanent tendinopathy in a 12 year old child. The parties agree that the Frye standard is to be applied. Thus, the burden is on the plaintiff to establish that the theory is generally accepted in the particular field to which it belongs. Plaintiff has failed to meet that burden.

The court must determine whether the opinion offered by the plaintiff's expert properly relates existing data, studies or literature to the plaintiff's situation. The focus of the inquiry [*2]should be whether a reasonable quantum of legitimate support exists in the literature for the expert's views. It is not necessary that the underlying support for the theory of causation consist of cases or studies considering circumstances exactly parallel to those under consideration. It is sufficient if a synthesis of various studies or cases reasonably permits the conclusion reached by the plaintiff's expert (Marsh v. Smythe, 12 AD2d 307, concurring opinion by J. Saxe). A complete absence of a single instance or a single reported case supporting the expert's theory requires the dismissal of the action (Stansky v. Ezersky, 228 AD2d 311). The law does not intend that the less that is known about a disease the greater shall be the opportunity of recovery in court (Miller v. National Cabinet Co., 8 NY2d 277,289).

Again, Stier has no personal experience with this issue. He has never done any research regarding fluoroquinolones, although he has published many papers on many other issues. Prior to being retained by plaintiff in this case, he had never read any articles on the subject. As a Ph.D., he has never treated patients with plaintiff's conditions and has never been involved in the decision to prescribe cipro.

While he testified that his search revealed research that showed that fluoroquinilones are known to cause injury, he failed to make any distinction between the types of injuries caused, such as tendinopathy, arthropathy, arthralgia, ruptured tendons or tendinitis, or the different types of fluoroquinolones, such as norfloxacin, ofloxacin, pefloxacin, levofloxacin and ciprofloxacin.

His literature search was not complete. As established on cross-examination, there were a number of articles that he either did not find or did not discuss that did not support his position.

For example, in an article entitled "Achilles Tendinitis Associated with Fluoroquinolone" by van der Linden, et al.,^[FN1] the authors report that no significant association was found for ciprofloxacin or norfloxacin. They go on to say that no association was found with the other types of tendinitis for the different fluoroquinolone agents other than oflaxacin.

In "Fluoroquinolone Use in Children,"^[FN2] the authors conclude that a comprehensive review including over 7000 children (5 days to 24 years) who received cipro, ofloxacin or nalidixic acid failed to show any association between quinolone use and arthropathy or bone or joint sequelae.

In "Fluoroquinolone Antibiotics in Infants and Children,"^[FN3] the author concludes that there is no unequivocal documentation of quinolone induced arthropathy in patients as described in juvenile animals; clinical observations temporally related to quinolone use are reversible episodes of arthralgia that do not lead to long term sequelae when the agents are discontinued; and the incidence of tendinopathy is very low, especially in children.

He also did not establish that injuries caused to adult populations by cipro can also be caused to children. While he opined that there is no difference in the effects on adults and [*3]children, he failed to cite any paper to support this position. He talked about a safety profile that he had read about, but says that he "believed" that it refers to the adverse effects of fluoroquinolones, again with no citation to any articles. In an article with which he was not familiar, "Quinolone Arthropathy in Animals Versus Children,"^[FN4] the authors state that their comprehensive review of published data leads to the conclusion that quinolone arthropathy, as described in juvenile animals, is to date not convincingly correlated with use of these compounds in children and adolescents.

He also did not establish that there is a condition known as "permanent tendinitis," the specific condition alleged by plaintiff. When asked whether a fluoroquinolone can cause a long term weakening in the structure and the integrity of a tendon in a human, he said that fluoroquinolones can cause long standing tendinopathy and that tendinitis is a subset of tendinopathy. He then referenced a paper by Lewis, written in 1999,^[FN5] to support his position that tendonopathies can be permanent. Review of that paper reveals that it was a report of bilateral Achilles tendinitis in an 83 year old woman caused by levofloxacin. It includes a table of cases of tendonopathies. Only one case involves tendinitis caused by cipro, involving a person of unknown age, and that resolved in six weeks. The article also mentions several risk factors, none of which are present in this case. No children were involved in this study. No other articles he relied on made reference to a permanent tendinitis.

When asked whether it was his opinion that it is generally accepted within the medical community that cipro can cause tendinitis in a twelve year old with permanent sequelae, he answered equivocally, "I think it's underappreciated. I think it can, but ." He did not cite to any study that supported the claim that tendinitis can be permanent. In fact, he referred to a paper by Kubin,^[FN6] which said that data clearly suggests that the administration of cipro to children is effective and safe. He specifically referenced Table 1, which did not mention tendinopathy as an adverse effect, only arthralgia, which is a general term for any joint pain. Several papers submitted, however, clearly indicate that the sequelae are reversible and generally not long-standing. None refer to any permanency.

He acknowledges that a theory must be rigorously tested before it can be generally accepted in the scientific community but agrees that this has not been done here. He thinks that the cause of this class of injury is underappreciated and thus not subject to more testing. He agrees that the idea that cipro can cause permanent tendinitis to a child has never been tested. He says, however, that "the absence of evidence is not evidence of absence." Unfortunately, plaintiff has the burden of proof and the absence of evidence is fatal to her claim of general acceptance of her theory.

This absence of evidence on behalf of the plaintiff is confirmed by the testimony of Dr. [*4]Hammerschlag, who testified on behalf of the defendants. It is her opinion, based upon her experience and a review of the literature, that there is no condition of permanent tendinitis and that cipro does not cause tendinitis in children. She does not believe that one can extrapolate any conclusion regarding children from one in vitro study of an adult tendon cell or from studies involving puppies or baby rats. There is no study that concludes that fluoroquinolones, or cipro in particular, cause permanent tendinitis in children and no data to support an opinion that fluoroquinolone induced tendinopathy is under-reported.

On cross-examination, plaintiff's counsel referred to the article by Kubin,6 but the witness pointed out that this article refers to cases of arthralgia, which is not even arthropathy and not relevant. Plaintiff referenced an article by Olaf Burkhardt, et al.^[FN7] which states that fluoroquinolone-induced tendinopathy is rare but under-reported. Hammerschlag pointed out that they did not provide any evidence to support their assertion of under-reporting. The next article that plaintiff inquired about is by Fish,^[FN8] which the witness characterized as full of misstatements. Plaintiff asked about the article by Lewis,5 specifically the statement that the length of recovery from tendinitis and tendon rupture is variable and occasionally the disability is permanent. Hammerschlag pointed out that there was no reference for that statement. In fact, a review of Table 1 shows that all cases of tendinitis listed, all of which involved adults, resolved. In an article by Pierfitte and Royer,^[FN9] which referenced 15 cases of cipro induced tendinitis, the longest recovery period in cases with known outcomes was two months. In a paper by Royer,^[FN10] the author says that the outcome of the side effects is favorable in 79% of the cases but does not distinguish among all the possible side effects, which include not just bone and joint problems. In another related paper, by Royer, Pierfitte and Netter,^[FN11] while the authors reference 31 cases of tendon ruptures and 69 cases of tendinitis and 13 cases with persistent symptoms during more than two months, they do not indicate whether those 13 had tendinitis or tendon ruptures. An article by Sendzik, et al.,^[FN12] was about an in vitro study of a piece of tendon from a middle-aged male, from which Hammerschlag says you cannot extrapolate to this plaintiff. An article by van [*5]der Linden, et al.^[FN13] suggests that fluoroquinolone-associated tendon disorders are more common in patients over 60 years of age. In cases where there was not full recovery at follow up, the authors did not indicate which of those patients might have had rupture and the persistence of follow up is not given. Finally, an article by Williams, et al.,^[FN14] describes an in vitro study of dog tendon tissue. The authors conclude only that certain effects of cipro may play a role in the development of tendinitis. This clearly does constitute general acceptance of the theory.

While cipro may cause tendinitis in adults, that is insufficient to establish that there is general acceptance of a theory that cipro is a competent producing cause of permanent tendinitis in children. A synthesis of the various studies reviewed does not support plaintiff's claim. There are too many variables regarding the type of fluoroquinolone used, the age of the patient, the type of injury and the duration of the injury. Thus, there is not a reasonable quantum of legitimate support in the literature to support Stier's opinion.

Accordingly, plaintiff is precluded from offering evidence of this theory at trial.

This constitutes the decision and order of the Court.

Dated: September 22, 2006________________________________

STANLEY GREEN, J.S.C.