Sara J. Kinkaid v. Silvio Inzucchi, M.D., Yale School of Medicine (2013)

MEMORANDUM OF DECISION RE APPLICATION TO COMPEL APPEARANCE AND COMPLIANCE WITH SUBPOENA ISSUES UNDER FOREIGN COMMISSION AND/OR FOR CAPIAS

Since 2005, the defendant, Yale School of Medicine,¹ has been conducting an eleven-year,² double-blind Insulin Resistance Intervention after Stroke [“IRIS”] trial [“the study” or “the IRIS study”], funded by the National Institute of Neurological Disorders and Stroke [“NINDS”], a part of the National Institutes of Health [“NIH”]. The study seeks to determine whether a drug, pioglitazone, when compared to a placebo, is effective in lowering the risk for stroke or myocardial infarction among non-diabetic persons who have suffered recent ischemic stroke or transient ischemic attack and are insulin resistant.   Pioglitazone is marketed under the prescription trade name “Actos.”   For the purposes of this memorandum, both pioglitazone and placebo will henceforth be referred to as “the drug” unless specifically identified as one or the other.

The plaintiff, Sara J. Kinkaid, alleges that she suffers from bladder cancer as the result of taking Actos.   Ms. Kinkaid, who is not an IRIS study participant, is maintaining an action against the manufacturer of Actos in another state.   She is one of approximately 100 plaintiffs in many different venues who are represented by the same counsel in actions against the manufacturer of Actos.   As represented by the plaintiff's counsel, the plaintiff is seeking data from this clinical trial to support her position that there is a causal relationship between the consumption of pioglitazone and bladder cancer.

Through a subpoena issued pursuant to a foreign commission, the plaintiff has filed an application seeking to compel certain discovery from the defendant as to the incidence of bladder cancer occurring in those patients who are or have been participating in the IRIS study.   To date, eleven of 3,876 participants in the study have been diagnosed with bladder cancer.   The defendant has agreed to provide the plaintiff with certain information as to the eleven, including site code, patient number, dates of treatment, date of event (diagnosis of cancer), severity of the cancer, its resolution and a summary of the basis for the diagnosis.

The plaintiff seeks further discovery as to the eleven instances, either specific identity of the number of participants diagnosed with bladder cancer who received pioglitazone together with a summary report of their medical history or, alternatively, the number of diagnosed participants in treatment arm “A” versus treatment arm “B” without disclosure as to which treatment arm was pioglitazone and which was the placebo.

The defendant claims it is not privy to the disputed information requested by the plaintiff, although it concedes that such information can be obtained.   The individually specific data sought by the defendant is known to a “study biostatistician,” who is located at a federal statistical center.   The study biostatistician aggregates the data and twice yearly reports it to an independent Data Safety and Monitoring Board [DSMB], selected by NINDS, in the form of treatment arm “A” versus treatment arm “B.” The plaintiff has not sought discovery of this information directly from the study biostatistician.

As to the plaintiff's fall back request of data as to treatment arm “A” versus treatment arm “B,” there are two entities that have such information:  the study biostatistician and the DSMB. The DSMB, biannually during the course of the study, reviews with the study statistician the reports of the data of treatment arm “A” versus treatment arm “B” and the occurrence of bladder cancer within those treatment arms.

In this study, since 2011, the DSMB has requested of, and reviewed in closed session with, the biostatistician a detailed table of information including the medical history and the actual drug assignments of these participants.   In other words, the DSMB knows which drug each individual bladder cancer patients has been assigned.   To date, the DSMB has at no time determined that there are safety concerns with the study.   The plaintiff has not sought discovery of the treatment arm data reports directly from either the study statistician or the DSMB.

The defendant has objected to the plaintiff's application, asserting that any discovery into the IRIS study will require unblinding, adversely affect the efficacy of the double-blind study.³  The defendant argues that disclosure of the aggregate number will jeopardize the integrity of the double-blind study.   The individual participants who have contracted bladder cancer no longer receive pioglitazone or placebo, but remain in the study and continue to participate in monitoring and reporting.   The defendant is concerned that, should these participants become aware as to their status as taking pioglitazone or a placebo, either they may leave the study or their monitoring and reporting, which had been assured by the double blinding, would be compromised by bias.   Either would have a negative impact on the integrity of the study.   The defendant also expresses concern that publication of the data as to these eleven participants may cause other participants to withdraw from the study, again compromising its integrity.   Lastly, the defendant objects to disclosure because such deviation from the study's protocol and principles of good clinical practice for research will also compromise the study's integrity.

“The granting or denial of a discovery request rests in the sound discretion of the court” (internal quotation marks omitted);  Standard Tallow Corp. v. Jowdy, 190 Conn. 48, 57, 459 A.2d 503 (1983);  though this discretion is limited by the Practice Book's rules on discovery.   See id., 57–60, citing Practice Book §§ 217 through 221 (now §§ 13–2 through 13–5).

Practice Book § 13–2 provides in relevant part:  “In any civil action ․ where the judicial authority finds it reasonably probable that evidence outside the record will be required, a party may obtain in accordance with the provisions of this chapter discovery of information or disclosure, production and inspection of papers, books, documents and electronically stored information material to the subject matter involved in the pending action, which are not privileged, whether the discovery or disclosure relates to the claim or defense of the party seeking discovery or to the claim or defense of any other party, and which are within the knowledge, possession or power of the party or person to whom the discovery is addressed.   Discovery shall be permitted if the disclosure sought would be of assistance in the prosecution or defense of the action and if it can be provided by the disclosing party or person with substantially greater facility than it could otherwise be obtained by the party seeking disclosure.   It shall not be ground for objection that the information sought will be inadmissible at trial if the information sought appears reasonably calculated to lead to the discovery of admissible evidence ․”

Practice Book § 1–8 provides:  “The design of these rules being to facilitate business and advance justice, they will be interpreted liberally in any case where it shall be manifest that a strict adherence to them will work surprise or injustice.”

The defendant in this action did not file a motion for protective order pursuant to Practice Book § 13–5.   Rather, the defendant filed an objection to the plaintiff's “application to compel appearance and compliance with subpoena issued under foreign commission and/or for capias.”   Because of the rather unique presentation of this issue, the court treats the defendant's objection to the application as it would a motion for protective order made pursuant to Practice Book § 13–5.

Practice Book § 13–5 states in relevant part:  “Upon motion by a party from whom discovery is sought and for good cause shown, the judicial authority may make any order which justice requires to protect a party from annoyance, embarrassment, oppression, or undue burden or expense, including one or more of the following:  (1) that the discovery not be had;  (2) that the discovery may be had only on specific terms and conditions, including a designation of the time or place;  (3) that the discovery may be had only by a method of discovery other than that selected by the party seeking discovery;  (4) that certain matters not be inquired into or that the scope of discovery be limited to certain matters ․ (7) that a trade secret or other confidential research, development or commercial information not be disclosed or be disclosed only in a designated way.”

Under Practice Book § 13–5, the party seeking the protective order is required to show good cause.   The courts have defined good cause as “a sound basis or legitimate need to take judicial action.”  Welch v. Welch, 48 Conn.Sup. 19, 828 A.2d 707 (2003) [34 Conn. L. Rptr. 171].  “Good cause must be based upon a particular and specific demonstration of fact, as distinguished from stereotyped and conclusory statements.”  Id. at 20.  “Whether or not ‘good cause’ exists for entry of a protective order must depend on the facts and circumstances of a particular case.”   Carrier Corp. v. Home Insurance Co., Superior Court, judicial district of Hartford–New Britain at Hartford, Docket No. CV 88352383 S (February 11, 1992, Schaller, J.) [6 Conn. L. Rptr. 3]. “To determine whether good cause exists, courts balance ‘the need for information against the injury that might result if uncontrolled disclosure is compelled.’  “ In re Zyprexa Injunction, 474 F.Sup.2d 385, 413–16 (E.D.N.Y.2007) (quoting Pansy v. Borough of Stroudsburg, 23 F.3d 772, 787 (3d Cir.1994)).

A hearing over the course of three days was conducted by the court.   The court makes the following findings.   The discovery sought by the plaintiff is potentially of benefit to the plaintiff if the information obtained can be utilized by the plaintiff's experts to establish a causal connection between pioglitazone and bladder cancer.   The actual data sought by the plaintiff from the defendant is already in the possession of the study statistician and the treatment arm results are in the possession of both the study statistician and the DSMB. The plaintiff has chosen not to seek discovery from these two sources.   Rather, the plaintiff seeks to obtain the discovery from this defendant, who would, in turn, have to obtain the discovery from one of these two sources.   The court finds that the plaintiff purposefully has chosen to obtain the information from this defendant through this state forum rather than from one of the direct sources through presumably a federal forum.

The court finds that the DSMB, which is responsible for assuring the scientific conduct and the safety of the study, has reviewed the treatment arm date biannually, has reviewed the actual treatment assignments since 2011 and has not indicated in any of its reports that it has concerns regarding the nexus between pioglitazone and bladder cancer.   The court notes that, other than an FDA report, the plaintiff has presented no evidence or testimony in support of its application.   In particular, the plaintiff has presented no evidence in support of its theory of the claimed nexus between pioglitazone and bladder cancer.

The court finds that the defendant has established good cause through testimony and evidence that the disclosure sought by the plaintiff will cause unblinding and will be detrimental to the integrity of the study.   The court finds that the defendant's witness, Walter N. Kernan, M.D., who is the study's principal investigator, has credibly testified that such unblinding will likely cause harm to the integrity of the study in the following ways:  (1) bias in the form of differential reporting could be introduced into the study through increased or decreased detection of outcome events if the participants or their treating investigators are made aware of this information;  (2) knowledge of the information could result in premature and incorrect inferences and erroneous impressions leading to withdrawal of participants from the study or causing the participants to stop taking the drug.   Over or misinterpretation of mid-study safety data may have a deleterious effect on study participants;  (3) the reputation and credibility of the study will suffer if the study's protocol is violated by unblinding;  (4) court ordered release of information may cause the independent DSMB to feel external pressure in its decisions as to trial safety;  and (5) court ordered unblinding will have a chilling effect on unbiased clinical studies.

The court sustains the defendant's objection on the basis that disclosure of the requested information may significantly jeopardize the integrity of a study which is well under way, has received significant federal funding and has been biannually reviewed for safety by an independent board.   While the court recognizes that the discovery of the sought information may potentially be useful to the plaintiff if statistically significant, the risk of jeopardizing the integrity of the study outweighs the potential benefit to the plaintiff.

In balancing the equities, the court has taken into consideration statements of the plaintiff's counsel concerning any protective order which the court may enter as to third-party disclosure.   At the outset of the hearing, counsel for the plaintiff assured the court that the plaintiff “would agree to a restrictive protective order with respect to any information which is produced over to us.”   On the second day of the hearing, the court asked substitute counsel for the plaintiff if he had further argument before the defendant called its witness.   Plaintiff's counsel bluntly informed the court that any protective order “would only go so far.”  “Should the cases go to trial, we expect to use the data ․ The protective order would only be for pretrial purposes.”   As some of these cases are currently on trial or post-trial, plaintiff's counsel has essentially asserted that counsel intends to ignore any restrictions placed by this court upon the use of such discovery, rendering any protective order of this court meaningless.

The court does not take umbrage that plaintiff's counsel has indicated that a protective order would be ignored.   It is clear that a protective order as to the information sought would preclude the plaintiff's experts from disclosing the information as a basis for their opinions, rendering utilization of the information impossible.   Therefore, it would be impossible to honor a protective order and also utilize the information obtained.

As it is clear that any information provided by the defendant which is beneficial to the plaintiff will necessarily be disclosed at trial, and as the court has given greater weight to the likely damage caused to the study by the disclosure of the information compared to the possible benefit to the plaintiff, the plaintiff's application to compel is denied and the defendant's objection to same is sustained.

The Court,

Robert E. Young, Judge

FOOTNOTES

FN1. By agreement of the parties, Yale University on behalf of Yale School of Medicine has been substituted as defendant in place of Silvio Inzucchi, M.D. (104.10)..  FN1. By agreement of the parties, Yale University on behalf of Yale School of Medicine has been substituted as defendant in place of Silvio Inzucchi, M.D. (104.10).

FN2. The study has been variously described as of eleven-, twelve- and fifteen-year duration..  FN2. The study has been variously described as of eleven-, twelve- and fifteen-year duration.

FN3. Blinding is intended to minimize the potential biases resulting from differences in management, treatment, or assessment of patients, or interpretation of results that could arise as a result of subject or investigator knowledge of the assigned treatment (drug or placebo).   A double-blind trial is one in which neither the participant nor the investigator is aware of the assigned treatment.   Guidance for Industry, E10 Choice of Control Group and Related Issues in Clinical Trials, Blinding (1.2.2), U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), May 2001..  FN3. Blinding is intended to minimize the potential biases resulting from differences in management, treatment, or assessment of patients, or interpretation of results that could arise as a result of subject or investigator knowledge of the assigned treatment (drug or placebo).   A double-blind trial is one in which neither the participant nor the investigator is aware of the assigned treatment.   Guidance for Industry, E10 Choice of Control Group and Related Issues in Clinical Trials, Blinding (1.2.2), U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), May 2001.

Young, Robert E., J.