Novartis’ Whistleblower Alleges Problems With Clinical Trial Safety Reporting

And I was hoping that the whistleblower case alluded to last week was just a Cafe Pharma rumor.  Unfortunately I was wrong and David Olagunju, former global director of oncology statistical reporting and standards reporting at Novartis, has filed a whistleblower case against the company in New Jersey.  He also seeks a Court Order, "compelling an audit of all drug study data compiled by Novartis and provided to FDA concerning Tasigna or any other drug using Novartis' clinical trial safety reporting system." Read Peter Rost and Ed Silverman , who have both interviewed Mr. Olagunju, for detailed reporting and analysis of the case, but David Olagunju's legal complaint reads like a tale of intrigue, involving the impact of corporate decentralization and downsizing, falsified data, managers with insufficient expertise overseeing those with greater knowledge of critical subject matter, and honest people being fired after disclosing problems,  for not being "team players."   I've always admired Novartis as one of the truly ethical pharma companies, so these allegations are extremely disturbing. Below, a brief verbatim excerpt from Dr. David Olagunju's legal complaint, but read Rost and Silverman (who have posted the entire complaint for download) for complete reporting and analysis.  Mr. Olagunju appears to be a very conscientious man, and apparently draws the same conclusion that most whistleblowers do:  "If you're young, think twice before doing this, you really shouldn't blow the whistle unless you're wealthy," he reportedly told Rost. And he advises anyone else who feels it is necessary to blow the whistle NOT go to the company. "Go straight to the authorities," he said. "If I had gone straight to authorities my life would've been so much easier right now," Olagunju says. "But if I meet my Maker tomorrow, at least I would have peace in my heart, because I've done the right thing." -AMS P.S. The following day, Novartis issued a formal response to Pharmalot blogger Ed Silverman. Following that blog entry, a nasty verbal duel with another blogger ensued in the Comments section. Gee, did someone manage to corner the market on the truth when we weren't looking? As Global Director of Oncology Statistical Reporting and Standards Reporting (SRS), plaintiff disclosed to Novartis' senior management the existence of improper statistical data being reported to the United States Food and Drug Administration (FDA), violations of established ethical standards concerning the recording and reporting of data, the failure to follow proper statistical protocols when reporting drug study data and violations of policies and procedures established to safeguard drug study participants and consumers of pharmaceutical products. In response to Plaintiffs complaints and in retaliation for his refusal to take part in Novartis' illegal activities and violations of public policy, he was harassed, threatened and ultimately terminated from his position at Novartis. Plaintiff seeks an Order compelling an audit of all drug study data compiled by Novartis and provided to the FDA concerning Tasigna or any other drugs utilizing Novartis's current clinical trial safety reporting system, otherwise known as Standard Tables and Listings (STL) . Plaintiff also seeks compensatory and punitive damages as a result of Novartis' willful and intentional actions and inactions .During Plaintiffs first year at Novartis, he worked as the Global Director of Biostatistics and Statistical Reporting Standards . Plaintiff reported directly to the Global Executive Directorof Statistical Reporting . In December of 2005, Novartis decentralized its Biostatistics and Statistical Reporting functions relating to Oncology to the Oncology Business Unit . In February,2006, plaintiff was offered and accepted the position of Global Director of Oncology Statistical Reporting and Standards (SRS) . Although he resided in Randolph, New Jersey and worked out of Novartis' Florham Park, New Jersey offices, Plaintiffs duties included responsibility forcompany activities throughout the United States, Switzerland, India and Japan.

In May of 2006, Kannan Natarajan was hired by Novartis as Vice President of Oncology Biostatistics & Statistical Reporting and became Plaintiffs immediate supervisor . Although he had previously served as Director of Cardiovascular Statistics at Bristol Meyers Squibb,Natarajan had little or no experience in managing statistical reporting or oncology statistics .

Statistical reporting requires a thorough understanding of the technology, programming and processes for capturing, storing and extracting and reporting data derived from clinical trials .

Due in part to his inexperience and the dismantling of the centralized B&SR department at Novartis, the amount of oversight needed to accumulate reliable and valid data was negatively impacted and compliance with proper protocol and FDA standards was not enforced .

Between May of 2006 and September of 2006, Plaintiff met with Natarajan and other Novartis officials on various occasions to discuss numerous violations in the hope of rectifying data errors and placing the various ongoing drug studies in compliance with FDA regulations .

On several occasions, Plaintiff discussed his concerns with Natarajan about the processing of drug study safety data within Novartis' Safety Reporting System (also known as the "STL") that was not formally validated prior to commissioning into production and generating data errors (i .e . empty files, poor documentation, incorrect date imputation for adverse events, wrong variables, and mismatched items) . These issues have serious impact on the reporting of safety data and have negative impact all of Novartis' clinical trials, not just the clinical trials for Tasigna . Novartis was advised as early as 2004 by their Global Director of Safety Reporting, that the "STL was not fully validated as per 21 CFR Part 11 guidelines" . Todate the system is obsolete and still generating inaccurate safety data that is being submitted to the FDA.

At the same time that Plaintiff was disclosing the reporting of improper safety data to Novartis officials, a contract programmer within the Oncology Business Unit complained of being forced to alter the calculation of duration of adverse side effects to enhance the appearance of Tasigna's safety in the clinical trials . It had become apparent amongst study team members that Tasigna had numerous cardiovascular side effects . By compressing the duration of adverseeffects, Novartis has exposed the public to a serious danger if this drug were to be approved .

When the contractor complained about being instructed to compress the safety data, Natarajan retaliated against him by withdrawing his offer of employment under the pretext that he did not get along with the study team . When Plaintiff objected to Natarajan's retaliatory action against the contractor, Natarajan threatened Plaintiff with termination .

Plaintiff also objected to the fraudulent attempt by Novartis' Development Leadership Team (DLT) to exaggerate Tasigna's Summary of Clinical Efficacy (SCE) and Summary of Clinical Safety (SCS) which are designed to demonstrate to the FDA the efficacy and safety of the drug.

The DLT's actions were enhanced through a last minute redefinition of Tasigna'sIntent to Treat (ITT) . Any deviation from the pre-defined statistical methodology negotiated with the FDA, including the definition of ITT, is improper . Nevertheless, the DLT (which consisted of a group of Vice Presidents, chaired by a Sr . Vice President of Oncology Development at Novartis) redefined the details of how patients were randomly assigned to treatment drugs, how the effect of the drugs were measured . reported statistically and negotiated with the FDA a few days prior to locking the data base . .-As a result of the actions of the DLT, the data provided to the FDA was not in accordance with the statistical protocol required by the FDA, and the FDA was not advised of these fundamental changes . Any changes or modifications to the FDA's protocol should result in a protocol amendment, approved and renegotiated with the FDA . Failure to do so could be considered fraud .

On March 31, 2006, the lead statistician for clinical pharmacology instructed a contract programmer to "hard code" the randomization codes for certain specified subjects of one of the Tasigna studies in a SAS program . This practice not only calls the validity of the study into serious doubt, it is in direct contradiction to the established procedures at Novartis, which state :

"No hard-coding is permitted in any programs used for the creation of analysis data sets, tables, listing or analyses that are intended for external reporting after data base lock { i.e. Clinical Study Reports (all phases), Publications, Abstracts, Clinical summaries { e.g. SCE, SCS, etc .} . B&SR is responsible to report the data on the data base and not to correct it. [emphasis in original]"

The type of study at issue in this particular instance was a SCS study relating to Tasigna .

Pursuant to Novartis' own guidelines, the data should not have been manipulated .

Plaintiff became aware of the hard coding of the study's randomization codes and voiced his concerns and objections to Natarajan and his Leadership Team . Natarajan expressed his frustration to Plaintiff that the contractor who was instructed to manipulate the randomizationcodes had the audacity to voice his opinion on what should or should not be done in a Novartis clinical trial . He seemed more upset however, that the contractor had documented the hard coding event and that Plaintiff was agreeing that the contractor was right in voicing his objections.

Plaintiff also voiced his concern regarding Novartis' failure to allocate resources sufficient to comply with legal standards and good clinical practice . Contrary to industry standards, Natarajan populated the department with many more statisticians than programmers .

Programmers and other department personnel were allocated to multiple projects and were pressured to neglect standards and procedures . As a result, the integrity of the data and reports suffered . Novartis was non responsive to Plaintiff's concerns .

Plaintiff also voiced concern to his superiors concerning changes to the Analysis Plan by the DLT without obtaining the required approvals or completing the necessary "RAP Change Request Approval Form" . Novartis' standard operating procedure requires that any changes tothe analysis plan be approved . When they are not approved it suggests to the FDA that Novartis may be altering the analysis as the scientists look at the data, see the results and change the methodology . Such a procedure is improper because these changes affect the numbers that are submitted to the FDA . Even over the objections of Plaintiff and other project team members who voiced their concern that such changes contradicted their ethical obligations, Novartis enforced there decision to modify analysis plan and data items . As a result, the veracity of the data submitted to the FDA was impacted .

The Lead Biostatistician on the Tasigna project affirmed many of Plaintiff's complaints to Novartis management . but still nothing changed at Novartis. As a result the danger to the public is substantial as Novartis continues to seek approval for Tasigna, a drug whose efficacy and safety design, data, and analysis were not well thought out, not validated and were hastily compiled. The same is so for all other Novartis drugs utilizing the same Safety Reporting System used in the Tasigna clinical trials .

The same lead Biostatistician also affirmed that the clinical data base for Tasigna was locked even though there were still pending data issues . He elaborated his concerns to Natarajan who continued to disregard this serious data integrity and reliability issue and permitted data of questionable reliability to be transmitted to the FDA .

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  • Ten years on and it was no different. SOPs not followed. Items had to be marked as validated even with known errors. Threat of job loss for not doing as you're told.

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