Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial

by Alison Bass

  Her experience in Florida had opened Firestein's eyes to the sometimes disastrous effects of antidepressants on children. Even so, she found it difficult to listen to the people calling the AG's office. Firestein remembered one phone call with particular clarity. It came from a mother in Michigan whose teenage daughter had been feeling a little depressed. She'd taken the girl to her own general practitioner, who had casually written out a prescription for Paxil. Almost immediately, the girl began acting strangely; she seemed agitated and angry all the time. One afternoon, she slashed her wrists with a knife and almost bled to death. Her mother got her to the ER just in time. As she later told Firestein, "My daughter was a hairsbreadth away from death. How could something like this have been allowed to happen?"

  Firestein had no easy answer for this mother or any of the people she spoke to. Not that she could have said much anyway. The case was still in litigation. She thanked the woman for calling and said she hoped the attorney general's action might bring about some needed reform, so that no other parents would have to suffer the way she had.

  Privately, though, Firestein was not so sanguine. It wouldn't surprise her if GlaxoSmithKline decided to fight the case in court. From the drug company's vantage point, the stakes were high. The damage to Glaxo's reputation from fighting a high-profile case like this could be long-lasting. But settling the case also had its risks. It would mean a tacit acknowledgment that the second-largest pharmaceutical company in the world had misled the public about the safety and efficacy of one of its blockbuster drugs. If Glaxo didn't settle and then won in court, that could embarrass Spitzer at a critical time in his gubernatorial campaign. Lord knows, Firestein didn't want to do that.

  Winning a spot on Spitzer's elite team had been the crowning moment in her career, something she still couldn't believe she'd achieved-and at the very same time that her doctors were counseling her to quit working. "Now that you're legally blind, you could qualify for disability," they told her. But she couldn't afford to stop working-not now that she was a breadwinner not only for herself, but for Ellie, the adopted child she and her sister were raising together. They had rescued Ellie from an orphanage in China in 1995, and although her sister had legal custody, the little girl treated Rosie, as she called her, as a second mom.

  The image of Ellie made Firestein smile, and the security guard who manned the checkpoint on the Broadway side of the Equitable's vast marble lobby nodded in return. The guards knew Firestein and her white cane. After 9/11, security at the building had been beefed up considerably, and everyone who worked in the Equitable had to show a laminated identity card to the security guards stationed at the two main entrances before gaining access to the elevator banks. But when Firestein had lost her card once, they let her through anyway. They were good about things like that.

  That afternoon, Firestein found herself back at the elevators, waiting for the visitors from GlaxoSmithKline. Tom Conway stood with her. Tall and ramrod thin, Conway had crisp, graying hair and a genial air. But Firestein knew that underneath his cheerful mien lay a prickly toughness, formed by decades of battling grafters, embezzlers, shoddy contractors, and the legions of other bad actors that ran afoul of New York's business laws.

  When their visitors arrived, Conway led the way single file down a narrow aisle and through two locked doors into the bureau's unpretentious warren of offices. Firestein brought up the rear. The third-floor office hadn't been painted in years; its walls were a dreary governmentissue gray. Dozens of cardboard boxes filled with old files were stacked in every available cranny, and the only modern piece of furniture visible was a photocopier. The consumer bureau had long been a backwater in Spitzer's high-profile shop. Most of the big news came out of his Investment Protection Bureau, which was constantly grabbing headlines in its pursuit of the banking and mutual funds industry. By contrast, the attorneys on the third floor spent most of their time going after sleazy contractors and loan sharks who preyed on unsuspecting New Yorkers. It was a mission that, while important, had pretty much kept the bureau out of the limelight-until now.

  THAT AFTERNOON, WHEN Conway and Firestein finally arrived at the designated conference room with their visitors, they found Shirley Stark, an assistant attorney general and Firestein's immediate supervisor, and Joe Baker, the head of the AG's Health Care Bureau, waiting for them.

  Conway, who was wearing a crisp blue shirt and navy pants, thanked the Glaxo attorneys for coming and made a joke about the drab surroundings. The conference room, which had dusty fluorescent ceiling lights and gray walls, looked like something out of a World War II interrogation room, complete with mostly empty metal bookcases stacked against the wall. The lead Glaxo attorney, whom everyone called Wick (short for Joseph Sedwick Sollers III), was a large, distinguished-looking man in his late forties with impeccably styled, graying hair. With his monogrammed cuffs and tailored suit, Wick, a partner at the national law firm of King and Spalding, looked distinctly out of place, as did Dwight Davis, who was fifty-one and also a partner at King and Spalding. Davis was wearing a respectable navy blue suit and red tie, but his attire seemed downright dowdy next to the resplendently attired Wick. The third visitor, Frank Rockhold, a senior vice president for biomedical data sciences at GlaxoSmithKline, also paled in comparison. None of the assistant AGs in the room could even remember what Rockhold looked like.

  All three men sat down on one side of the conference table, their backs to the metal bookcases. Conway took his place at the end of the table farthest from the door, with Firestein next to him. Stark, a slender, dark-haired woman in her late forties, sat next to Firestein, and Baker, an affable-looking man with stylish black glasses and a receding hairline, parked himself directly across from Wick.

  Conway began by talking about what the AG's office needed to see from GlaxoSmithKline in order to settle the case. The state prosecutors had already made it clear they wanted more than money on the table. Their real goal was to convince the pharmaceutical company to post the results of its clinical drug trials on a publicly available Web site. As Eliot Spitzer was fond of saying, "This case is not about money. As bad as all the Wall Street cases were, that was about money. This is about people's health, where the consequences of mischaracterizing the impact of a particular drug are dramatically more important." To prevent the kind of mischaracterization Spitzer and his team believed had occurred in the pediatric Paxil studies, they felt strongly that Glaxo should be required to post the detailed results of its clinical drug studies on a public Web site.

  Smiling benignly at the visitors from GlaxoSmithKline, Conway restated that demand: there would be no settlement without a comprehensive clinical registry. He then turned to the blond-haired attorney sitting next to him and said, "Rose, you want to talk more about that?"

  Firestein nodded and leaned forward. The online registry, she said, would have to include not just the results but other key data from the drug company's studies of human patients, known as clinical trials. To win FDA approval to market a drug, pharmaceutical companies first must test its safety and effectiveness in animals (usually rodents) and then determine whether the drug is safe or toxic in humans, using a small sample of healthy volunteers. They perform these Phase 2 studies to examine the drug's effects on the body's metabolism and see what kind of side effects it causes. Drug companies were required to submit their Phase 2 studies to the FDA, but they rarely published them in medical journals or otherwise made them available to the public.

  The pharmaceuticals were not required to publicize any of their test results, including the large-scale clinical trials that they conducted on people to compare the effectiveness of the drug to either a sugar pill or older medicines already on the market. These Phase 3 and 4 studies had to be submitted to the FDA, of course, but the information in them was considered proprietary and the FDA rarely made the results public. So the drug companies could pick and choose which of their clinical trials to publicize and which to suppress.

  But now the AG's office was
demanding that GlaxoSmithKline post pertinent clinical data from all its Phase 2, Phase 3, and Phase 4 trials after a certain date on a publicly available Web site. And that wasn't all. As Firestein explained to the three men sitting across from her, the posted summaries also had to contain detailed data on adverse side effects as well as information on efficacy and other key protocols.

  Rockhold, the senior VP from Glaxo, interrupted her.

  "You know we can't do that," he said. "If we post that kind of detail on the Web, we won't be able to get published in the journals."

  "I understand your concern," Firestein said, "but we think something can be worked out. Perhaps the data could be posted online concurrently with the study's publication in the journal."

  Rockhold tightened his lips.

  "Look, I want you to know that we've decided to post our registry this Friday," he said. "We've already determined what the content will be"

  Firestein's mouth went dry. That was two days from now. Firestein knew that a quick posting by G1axoSmithKline would make it harder for the AG's office to convince a judge that a truly comprehensive registry was needed. And if the case was settled without specific terms spelled out for the registry, the AG's office would have no legal standing to enforce a complete listing of all the clinical studies, those with negative results as well as those with positive. "Glaxo could easily cream the good studies and leave out the bad ones," Firestein later explained. "And if they did something that seemed reasonable on the surface, that would make it that much more difficult for a court to say they violated the law." The chance to bring real reform to an entrenched industry would be lost.

  Before Firestein could open her mouth to say something, Tom Conway spoke up.

  "If you post it, we'll see you in court," he said in a cold voice that carried an unmistakable challenge.

  And then he stood up. Baker and Stark stood up too, and Firestein had no choice but to join them. But her insides were churning with anger and a sinking sense of despair. Firestein knew she cared too much about this case. The last time she had invested this much in a lawsuit had been in the 1980s, when, after winning that resegregation case against Tattnall County in Georgia, she and her colleagues at the Georgia Legal Services had sued the entire state. They had accused the Georgia Department of Education and school districts throughout the state of essentially the same practice: assigning black children with borderline IQs to warehouselike classes for the mentally retarded while white children with the same test scores were given specific learning disability instruction. Firestein poured everything she had into the statewide complaint, traveling all over Georgia's hinterlands to take depositions. She even camped in a tent on several occasions when she couldn't find lodging. But after all that hard work, her team lost the case in the Eleventh Circuit Court.

  The defeat had broken Firestein's heart. She left Georgia and moved to New York to live with her sister in Queens, swearing never again to go into a courtroom. She took culinary lessons with the idea of becoming a chef, until one day it dawned on her that working in the restaurant business was even harder than litigating cases. Now here she was on the cusp of another monumental legal battle, and Conway was going to ruin everything with his all-or-nothing ploy. They'd never get GlaxoSmithKline to the bargaining table again. But her boss had made his move, and she had to show a united front. Sick with disappointment and frustration, Firestein followed her three colleagues out of the room.

  Howard hung up the phone and sighed. She sat back in her chair and looked out the dirt-encrusted window of her office. Her aging Saab had been making strange noises that morning, so she had driven it directly to the Swedish Motors shop a few blocks from her office. And now the mechanic was telling her it needed a new transmission and the job would take at least three days, maybe four. That car spent more time in the garage than it did on the road! Donna glanced at her watch; it was just after 4 p.m. Maria would be home from school. Howard had left a casserole for her to put in the oven, but she knew how anxious her daughter could become when she was late.

  Howard's office was in the Duncan Building, a dust-red brick edifice that was part of the sprawling Brown-Butler Hospital campus on the east side of Providence. Duncan had been built in 1846 as a mental asylum. The offices on the south side of the building had big bay windows, through which light poured in on sunny days. But on the north side, where Howard's office sat, the windows were tall and narrow, too narrow for an adult body to easily fit through. When she first came to work here, Howard had speculated to co-workers that the building had probably been designed to offer palliative care for patients at a time when real medical treatment didn't exist. The depressive patients were probably kept on the south side, where it was hoped that all that sunlight would cheer them up, while the manic patients were kept on the north side, at least until they settled down.

  "I guess I just haven't settled down yet," Howard would add, almost always eliciting a laugh, particularly from people who didn't know about her own family history. And Howard would laugh too, her laugh as light and silvery as chimes. Among her colleagues at Brown, she had made no secret of the fact that Maria, her adopted daughter, had manic depression. But she had told no one of her own more recent diagnosis. Howard too suffered from bipolar disorder. In the fall of 1991, after Maria left for a boarding school in Connecticut for emotionally troubled girls, Howard felt strangely disconnected and confused, as if her brain had switched to slow. The doctor prescribed Prozac. Two months later, Donna found herself staying up all night for days at a time, her thoughts racing, her senses acutely, uncomfortably aware of every sound, every smell. Howard had had these periods before- during college, she would stay up nights to finish papers and feel extraordinarily creative and energetic for weeks at a time-but nothing this intense or disorienting. She later learned that in people who, like her, were predisposed to bipolar disorder, a sudden switch to mania was often triggered by exposure to an antidepressant. She began taking the antipsychotic Depakote to tamp down what sounded like a buzz of locusts in her brain.

  Donna Howard was not the kind of person most people think of when they think of mental illness. Her colleagues saw her as a competent and levelheaded administrator. At the acute care hospital in New Bedford, she had managed a staff of thirty employees and a budget of $750,000. When her doctor diagnosed Howard with bipolar disorder, he said, "Until now, you've been a supercompetent, superresponsible person. You've been able to make your disorder work for you. But you can't do it on your own anymore. You need medication to manage this illness."

  Howard had taken the assistant administrator job in Brown's psychiatry department in large part because of her and her daughter's diagnoses. She was eager to work at an institution where so much important research into the workings of the human brain was taking place.

  That had been eleven months ago. Now it was September 1995, and she was desperate to leave Brown. She had already started casting around for another job. But first she needed a ride home. Who did she know who lived out her way? Howard commuted an hour every day from one of the forgotten coastal towns in southeastern Massachusetts whose residents enjoyed the same mild Gulf Stream waters as Falmouth and Martha's Vineyard, but at considerably cheaper real estate prices.

  As she gazed out the window of her office in Duncan, Howard remembered what one of her co-workers had told her the other day: Alice Tangredi-Hannon, Brown's director of research administration, lived in Marion, an upscale coastal town near hers. Howard had never met the woman, but the researchers and support staff at Brown lived in fear of her. Tangredi-Hannon held the power of life and death over their research projects. It was her job to ensure that the university's researchers lived up to the letter and spirit of the informed consent rules for research involving human subjects. And she was vigilant in her duties. Howard had seen a few of the terse memos Tangredi-Hannon fired at Dr. Martin Keller, the head of Brown's psychiatry department. In one memo, in which the research director was responding to notice of a suicide attem
pt by a teenage patient enrolled in one of Keller's clinical trials, her tone bordered on scolding.

  We are in receipt of your memo ... outlining an adverse event which took place on January 19, 1995. Please provide us with a copy of the full written summary of the adverse experience that you are required to submit to the [pharmaceutical] sponsor ... The above referenced memo did not include your signature. Please sign any future correspondence to our office."

  The woman couldn't be that bad, Howard decided, if she was willing to take on Marty K. She looked up Tangredi-Hannon's extension and dialed it. To her surprise, the administrator picked up the phone herself and sounded quite pleasant. After hearing where Howard lived, she said, "I'd be happy to give you a ride home"

  "Are you sure? I don't want to impose-," Howard began. The confident voice on the other end of the phone cut her off.

  "No imposition at all! It's right on my way home"

  TANGREDI-HANNON KEPT her waiting only a few minutes. She pulled up to the front entrance of Duncan in a silver Infiniti. It was after five and the windows of the campus buildings glowed with the sun's dying brilliance. It was the time of day Howard loved best, knowing she was on her way home to Maria. Her daughter, who had left boarding school and was living at home again, was not doing very well. For a while, Maria had responded to lithium and then to Depakote. But Maria was what is known in the field as medication refractory: she might respond to a new drug for three to six months, but then it almost invariably stopped working. By the time she turned eighteen, Maria had run through almost every antidepressant and mood stabilizer on the market, and that summer, despite her mother's misgivings, she underwent seven electroconvulsive therapy (ECT) treatments. The ECT worked for several months, but by December of that year, her symptoms had roared back. Her doctor then started Maria on a powerful new mood stabilizer known as Clozaril, which seemed to work. She was still taking Clozaril when her mother's Saab developed its hiccups.