To view original article click here
Baum, Hedlund, Aristei & Goldman
February 8, 2018
Boston, Massachusetts – massa The law firm of Baum, Hedlund, Aristei & Goldman has sent a letter and memorandum to the U.S. Attorney’s Office (USAO) for the District of Massachusetts calling for the reopening of its investigation and prosecution of Forest Laboratories Inc. and its subsidiary, Forest Pharmaceuticals Inc. Both companies are now owned by Allergan PLC.
The memorandum includes 79 supporting exhibits detailing how Forest deliberately misled the U.S. Food and Drug Administration (FDA), the Department of Justice (DOJ), the medical community, and parents regarding two widely-prescribed antidepressant medications, Celexa (citalopram) and Lexapro (escitalopram) for use in children and adolescents.
The government concluded an investigation of the company’s off-label promotion of Celexa and Lexapro for pediatric use in 2010 when a settlement was reached with an agreement that Forest would pay the government more than $313 million dollars. The government’s investigation of Forest focused on the drug maker’s illegal off-label promotion of a supposedly positive Celexa study (MD-18 or “Wagner study”) and suppression of a negative Celexa study (94404 or the “Lundbeck study,” also known as the “European Study). Documents unearthed during the course of a series of civil Celexa/Lexapro lawsuits conducted by Baum Hedlund in Boston, reveal a much deeper deception than the government ever suspected.
USAO and DOJ Did Not Have the Full Story When Civil and Criminal Charges Against Forest Were Settled
In 2010, Forest entered into a series of settlement agreements with the USAO for the District of Massachusetts. As part of the agreement, Forest pleaded guilty to one count of obstruction and two counts of distributing a misbranded drug under the Food, Drug, and Cosmetic Act. One count specifically related to Forest promoting the use of Celexa for use in children and adolescents between 1998 and 2002.
Forest also entered into a civil settlement agreement to resolve various qui tam False Claims Act lawsuits alleging pharmaceutical fraud through off-label promotion of Celexa and Lexapro for children and adolescents between 1998 and 2005.
Lastly, Forest entered into a five-year corporate integrity agreement to address its promotional conduct.
Each agreement was contingent on the others and each agreement required complete honesty from Forest. However, according to unsealed court documents obtained in litigation against Forest, the scope and extent of Forest’s fraud regarding the Celexa/Lexapro clinical trials was not properly disclosed before the 2010 settlement agreements. Per the evidence cited in the memo, Forest misrepresented material facts underlying the USAO’s investigation.
How Clinical Trials to Test the Efficacy of Medications Work
A drug’s efficacy is determined using double-blind randomized controlled trials (“DBRCTs”), which involve the systematic comparison of patients taking a drug and patients taking a placebo. Patients enrolled in the clinical trials are randomly assigned into two groups; one group takes the drug and the other takes a placebo. Neither the investigators nor the patient know which group each patient is in (i.e., they are “double blind”).
Once the study is complete, the benefit observed in the two groups is compared, and if the patients taking the drug meaningfully outperform the patients in the placebo group, the clinical trial is considered positive. On the other hand, if the drug does not outperform placebo, it is considered negative.
If either the investigator or the patient is unblinded during the clinical trial, it invalidates the data since there is no way to determine whether the effects observed are caused by the drug as opposed to other factors.
Blinding is intended to limit the occurrence of conscious and unconscious bias in the conduct and interpretation of a clinical trial. If either the investigator or the patient knows they are receiving the drug, that knowledge will likely influence their assessment. Numerous studies have confirmed this fact. Blinding is a vital factor in medication research.
Forest Knowingly Misled FDA on Celexa Clinical Trials
When the USAO settled with Forest in 2010, the government did not know that MD-18 only achieved a positive result through the improper inclusion of nine patients in the study for whom “the blind was unmistakenly [sic] violated” or, as Forest’s medical director put it, were “automatically unblinded” due to a dispensing error.
Evidence included in the memorandum shows that the “positive” MD-18 study was not positive. According to the memo, “MD-18 was only able to achieve a positive result by including nine patients in the study that were, as Forest’s medical director put it, ‘automatically unblinded’ due to a dispensing error.”
Upon learning about the dispensing error, Forest informed the FDA that the study would appropriately exclude the unblinded patients. However, when Forest realized that the unblinded patients needed to be included in the study to produce a positive result (i.e. show that Celexa outperformed a placebo), Forest put the unblinded patients back in the study and falsely told the FDA the patients were not actually unblinded.
Forest received the results of Study 94404 and MD-18 at approximately the same time (around July 16, 2001). According to the unsealed documents cited in the memo, the decision to suppress the results of Study 94404 and promote the results of MD-18 was deliberate.
In a draft letter to be sent to the FDA, Amy Rubin, a Forest Regulatory Affairs Manager, characterized the dispensing error that caused the patients to become unblinded as having “the potential to cause patient bias.” Dr. Charles Flicker, the Senior Medical Director overseeing MD-18, did not approve of this language:
“Altho ‘potential to cause bias’ is a masterful stroke of euphemism, I would be a little more up front about the fact that the integrity of the blind was unmistakenly [sic] violated.”
Rubin’s response to Dr. Flicker:
“Thanks for the compliement [sic]. Part of my job is to create ‘masterful’ euphemisms to protect Medical and Marketing.”
“Not only was the disclosure to the FDA dishonest, according to a Forest Regulatory Affairs manager, it was her job to mislead the FDA and protect medical and marketing,” says Baum Hedlund attorney Brent Wisner, who signed the firm’s letter to the USAO.
In the letter to the USAO, Baum Hedlund invokes testimony from Dr. Thomas Laughren, the former official at the FDA who reviewed the MD-18 study. According to Dr. Laughren, he believed at the time he reviewed the study that there had been no unblinding. When he saw the evidence included in the memo, Dr. Laughren testified that Forest did not honestly disclose the situation to him.
The material fact which played a role in the settlement agreements between Forest and the USAO—that Celexa Study MD-18 was positive—was, at the time, false, and Forest knew it. Worse, shortly before the settlement agreements were finalized, the FDA approved Forest antidepressant, Lexapro (considered a chemical cousin to Celexa), for use in adolescents based in part on the misrepresented MD-18 study.
Had Forest accurately disclosed MD-18 as negative, the FDA almost certainly would not have approved Lexapro for use in adolescents.
The USAO and the DOJ did not know the full story when the government settled the civil and criminal charges against Forest in 2010. According to the memo, “[u]nder the terms of the criminal plea, the USAO retains the right to reopen its prosecution if the plea agreement was based on or involved any falsehoods. The information and evidence set forth in this memorandum strongly support the reopening of the USAO’s prosecution of Forest, to hold Forest accountable for the fraud perpetrated on the FDA, the USAO, physicians, parents, and the medical/scientific community.”