Drumming at his office door. When he unlocked it, his son charged inside. “Daddy, we’re having spaghetti for dinner. Hurry. It’s getting dark.”
And it was. He’d been on the phone for almost five hours. Mother, father, brothers, sisters all arranging his life. Transportation. A medical position. A political stance. What choice do I have?
* * *
On what was to be his last night in America, Ahmed, never an emotional man, a man who, in fact, disdained emotions, found himself for the first time in his life overcome by feelings. He couldn’t describe them, but they’d started to accumulate as Alex played with his action figures and Nicole sat silently reading a book. He thought about everyone he’d miss. He would miss Nicole’s family. Her three brothers, their wives, their kids—Alex’s American cousins. But in Cairo, his son would have Egyptian cousins. Yes, Wati would be okay. But will I be okay without Nicole? Nicole, talk to me, please. I don’t want to leave you. But she sat in her usual chair in the living room, never looking up from her book.
Eventually, Ahmed gave up and went to bed, but not to sleep. Nicole waited another hour to come upstairs and silently lay down on her side of the bed. No words. No touch. Earlier he’d noticed that she’d removed the Band-Aid over her lip. She’d have no scar.
After tomorrow, would he ever see Nicole again? Not according to his father. But certainly, once he had Alex—he had to start calling him Wati—ensconced in the family compound, Nicole would beg him to let her live in Giza with his family. She loved their son, could not bear to be separated from him. Once Ahmed gained a foothold, he’d appeal to his mother to speak up for Nicole.
Even after that big fight, she’d shown her good intentions. She’d taken Alex to the Islamic Foundation School. She’d left the registration application, partially filled in, in plain sight for him to see. A reconciliatory move, but still, she had not spoken to him, not shown him the respect he was due in his home and at their office. She expected him to apologize—
Except for the Wednesday when she’d taken Alex to the school, Nicole had kept her usual schedule in the OR and in the office. But she gave him the silent treatment there, too. Normally, they’d confer on cases like normal partners. Not this week. And, no, he hadn’t yet told his wife and business partner that he’d been sued, again. The family of the woman who had coded in the hospital last week, claiming negligence. His third malpractice suit in nine months. Sure, she’d say, to try to reassure him, plastic surgeons are a high malpractice risk. But why always him? It had to be anti-Arab prejudice. Otherwise, why not include his partner, Nicole, in the suit? Well, after tomorrow, he wouldn’t have to deal with malpractice or any anti-Islamic sentiment.
Unable to sleep, unable to face the reality that he might never again see the beautiful blond woman sleeping in his bed, Ahmed reviewed what he’d learned this week about his country. He knew more than he’d let on to his family. Following instructions, he’d tackled the Internet.
Through Facebook, mainly, he’d familiarized himself with Dr. ElBaradei, a prospective challenger for Egyptian President. As former chief of the UN watchdog, IAEA, he counted among the four Egyptians ever to have won the Nobel Prize. After returning to Egypt in February, he’d announced what he called the National Association for Change. Via a flurry of Facebook postings, Ahmed learned that this new entity had released a statement, “Together for Change” known as “ElBaradei’s Seven Demands for Change.”
The seven demands made sense, Ahmed thought—a notion he would never share with his family. Mentally, he ticked them off:
1) terminate the state of emergency. Enacted in 1958—it was about time;
2) judiciary supervision of elections;
3) appoint election monitors;
4) equal media time for candidates;
5) grant ex-pat Egyptians the right to vote—he wasn’t so sure about that one;
6) two-term limit for President—Mubarak had been in office for twenty-nine years—spanning the Reagan, the Bush, the Clinton, the George W., and the Obama administrations;
7) voting with national identity cards to reduce fraud.
The state had tried to control ElBaradei’s growing popularity, banning him from the Egyptian media, but Twitter and Facebook postings escalated, creating unprecedented interaction between the presidential contender and any Egyptian with Internet access.
Over the course of one week, Ahmed had immersed himself in his country’s groundswell of opposition to Mubarak. Whenever he had a free moment, he’d close himself up at home or in his office to go on Facebook.
He followed the posts about the twenty-eight-year-old from Alexandria, Kullena Khaled Said, who had been beaten to death by two of Mubarak’s secret service agents. Horrifying photos; a viral response. Ahmed knew that many similar, unreported episodes had occurred, but this one had been photographed, documented, disseminated. A Facebook page entitled “My Name is Khaled Mohamed Said” rallied multiple “Silent Stand” protests throughout the country. Something big was happening in Egypt. Egyptians were taking a stand. His family was right to be concerned—about their wealth—about their safety. If Mubarak went down, they would go down. But how realistic is that possibility? And what does that mean for me?
Now as Ahmed reached out to lay a tentative hand on his wife’s exposed arm, he questioned his resolve. Can I leave her? Take our son? Submit to my father? A tear began to trickle down his cheek as he watched Nicole’s chest rise and fall. Asleep, oblivious to the devastation that would implode her life tomorrow.
CHAPTER TEN
NATALIE SAT AT the antique oak printer’s desk, sipping her Monday morning black coffee in the same office her mother had occupied until her retirement five years ago from Keystone Pharma. Same position—and office—her mom had occupied—how bizarre was that!—Executive Vice President, Research and Development. She’d been EVP nearly a year now. Left the rose-colored office decor much the same as her mom’s. She’d kept her maiden name when she’d married Rob; from Dr. Laura Nelson to Dr. Natalie Nelson. Strange how it all worked out, but it did, and she loved her job—both the medical research and the management aspects.
She’d been working on a New Drug Application—NDA—a thick sheaf of papers that waited undisturbed for review. She couldn’t focus. Couldn’t stop thinking about Nicole. She hadn’t seen her sister since they’d had lunch a week ago. Ahmed had hit her and she’d looked like shit. Natalie had made several attempts to set a time to get together, but each time Nicole had an excuse. Rob’s birthday might have been excuse-proof, if Rob hadn’t pleaded with her to just have a quiet dinner at home. Natalie determined that if she didn’t see her sister face-to-face during the current week, she and Rob would drop by Nicole and Ahmed’s house next weekend.
And Natalie was preoccupied, as well, with Rob. The Chapter 11 filing last Monday had hit him hard. Her garrulous, fun-loving husband seemed—empty. She was worried about depression. So much of his sense of self-worth was entwined with the business his dad had started and that Rob had worked so hard to expand as a tribute to his parents who had both died shortly after his dad retired. The shame of failure haunted him now. He couldn’t sleep. Didn’t eat. Had no interest in social affairs, family events. He should see a psychiatrist, she knew. She also knew that he’d go ballistic if she suggested it. Real men don’t see shrinks.
Her intercom buzzed and Natalie glanced at her watch. Time for the Monday morning staff meeting. Nine a.m. A tradition of her mother’s that she carried on. With a last sip of coffee, she picked up her meeting agenda and headed down the hall to the R&D Conference Room. Her staff—all but one—had already gathered. She poured herself another cup of coffee, chose a healthy-looking muffin, and took her seat at the head of the table.
“Where’s Dan?” she asked of no one in particular.
“Here!” Dan Booker rushed into the room, closing the door behind him, joining Natalie and his four colleagues to take his usual seat at the table. Impeccably dressed in pinstripe suit, muted t
ie, monogrammed shirt—but his hair looked like it hadn’t seen a comb; maybe a hint of stubble instead of his typical close shave.
“Sorry I’m late,” he said, spectacled eyes focused on Natalie. “Afraid we have a problem. Came up over the weekend. Worked all last night to get it together for this morning—didn’t want to call on Sunday night …”
Eyebrows rose as Booker extracted a manila folder from a leather portfolio, set it on the polished mahogany table, and removed his glasses.
Booker, experienced, older than Natalie by fifteen years, was a straight shooter, not taken to dramatics. He was first on today’s agenda—to report on the Phase IV study of Zomera, their new cancer drug—one that drastically diminished metastatic carcinomas. Could something have gone wrong in that study? Her mind instantly served up a buffet of unfortunate implications, both medical and financial.
“Yes?” Natalie prompted.
“Not good news, I’m afraid.”
“The Phase IV study?”
“Let me lay it all out,” Booker said, opening the folder. “I haven’t had time yet to do a formal report, so I’ll give you the basics.”
Natalie looked around the table at her five direct reports, her research team. A team she trusted, a team she had handpicked for their scientific expertise as well as their organizational skills.
“For God’s sake, Dan,” one of the team said, “you look like you need a night’s sleep. Let’s hear what’s up so you can go home and shave.”
Booker began to talk without referring to his notes. “As you all know, the Phase IV study for Zomera passed the one-year mark three months ago. The protocol called for an interim analysis at what would be the halfway mark of the Phase IV study.”
Drug development consists of three pre-approval phases. Phase I to test toxicity in a small group of healthy volunteers—although with cancer drugs sometimes actual cancer patients were used. Phase II to see if the drug actually worked in a limited number of carefully monitored patients. Phase III expanded the treatment sites and the number of patients until eventually, for Zomera, one thousand patients had received the drug in clinical studies.
The FDA often requires a post-approval—Phase IV—study to continue to observe large patient populations for rare side effects that would emerge once more patients had been treated with the drug in real-world circumstances. For Zomera, the real-world consisted of thousands of patients in fifty countries who had taken the promising trial-drug for advanced cancer.
Natalie knew of no problems with Zomera. Keystone Pharma had a rigorous adverse reaction reporting system. They were considered a model in the industry for their pharmacovigilance. What could Booker have found that had him so uptight?
“Two thousand patients were included in the interim cutoff,” Booker went on. “The data took a while to clean, tabulate, the usual, but the preliminary study report was on target—”
“Yes,” Natalie interrupted. “It’s on our agenda for you to present.”
“Sunday morning, I got a call,” Booker reported. “From the team handling the Zomera post-marketing study. They said I had to come to the office right away—something I needed to see. The team was all there, would be all day. So I went and—”
“Dan, get to the point,” Natalie said. “What’s this about?”
Booker paused, then announced, “The shit’s hit the fan. Okay? No joke.” His already-attentive audience seemed to listen harder.
“We found an unexpected number of deaths in the study,” Dan continued.
Everybody began talking at once; what wouldn’t Natalie have paid for a gavel.
“Impossible,” she said. This was the most effective drug against cancer on the market.
“Let me explain. The effect of Zomera on cancer is the same in the interim cutoff as it was in the pre-market studies. The only thing is that patients in the Zomera group are dying of … constipation. We know that five percent of the general population suffers from chronic constipation and that ten percent of patients taking Zomera do. Always made sense, since cancer patients are prescribed opioids, well known to cause constipation.”
“Of course, we know that,” Natalie said. Where was this going? “The point, Dan?”
“Ten percent of two thousand means two hundred patients. We have two hundred eight patients reported with constipation. And, of those, we have twenty deaths. Of those twenty deaths, fifteen were in remission—and all fifteen reported severe constipation.” He hastened to add, “And they all were taking powerful opioid analgesics.”
“So we’re curing their cancer and they end up dying of a common, often considered trivial, side effect?” Natalie said.
“What’s of interest in the Phase IV study, Natalie, is how inept doctors and patients are when it comes to managing chronic constipation. The twenty patients who died—here’s what they had—electrolyte imbalance caused by osmotic laxatives—kidney failure from enemas—rectal prolapse from straining—bleeding from rectal fissures. You name it, and it has to do with defecation; we’re seeing it in patients taking Zomera combined with opioids.”
Natalie leaned back in her chair, trying to think this through. What Dan was describing were side effects from treating the side effect—constipation. Not a direct, but an indirect, result of treating cancer pain with opioids. Pre-approval clinical trials are tightly controlled whereas post-approval trials more closely mirrored real life. And in real life, patients—and even their physicians—can treat constipation in dangerous ways. Either way you looked at it, Keystone had a problem.
“We’re curing cancer for God’s sake,” one of her staff said. “People—and their doctors—don’t know how to treat their simple constipation—their problem.” He added, “Or the companies’ problem who make laxatives.”
“We’re left with twenty deaths related to one side effect,” said Dan. “Even though for fifteen, their cancer was in remission.”
“That all has to be reported to the FDA,” said the guy responsible for regulatory affairs. “And immediately. Standard operating procedure for a life-threatening side effect.”
Damn, but he was right. This had to be reported within forty-eight hours. And it would be. But Natalie’s first job was to brief the CEO. Immediately. Not a happy prospect considering Zomera, after only one year on the market, had sales exceeding a billion dollars. Whatever the outcome, the impact on Keystone Pharma would not be good.
Natalie addressed her staff. “You all know that this is our highest-level priority. Pull together the report for the FDA. As I see it now, this will be our conclusion: these cases of constipation are not related to our drug; they are related to other entities used to treat the common condition of constipation. Schedule a meeting with the FDA for Wednesday. Request that the division director for both oncology and gastroenterology be there, as well as the director of drug safety.”
She surveyed her team. Confident that they all understood, she said, “I’m heading to the executive suite to tell Barney Black. I’ll say we think this can be handled by a label change, warning doctors and patients about the dangers of improper use of laxatives.”
As Natalie headed to her boss’ office, she could feel the thudding dread that came with reporting bad news about an important drug.
Barney Black, CEO of Keystone Pharma, came from a financial background, knew little about science, and depended on Natalie to educate him on all things medical and regulatory. He might look smooth in the hand-tailored three-piece suits he favored, but he was not without some rough edges. And he did not “discriminate” by sparing her his venomous temper because of her gender. She expected an explosive reaction.
Barney’s secretary was not pleased to observe Natalie walking purposefully toward her. “He just got here from the airport, Dr. Nelson. Back-to-back appointments all day.” She looked at her calendar. “Perhaps—”
“I have to see him now,” Natalie said. She knew she had a particular voice when she needed to sound in-charge. “I just learned that we have a pr
oblem with Zomera. He’ll want—”
“In that case, better go right in. Surprise him.”
Not a good surprise—wouldn’t be long before his voice would boom through the long corridor.
“Natalie!” Barney did not bother to rise. Natalie was pleased. She did not want to be treated differently from the males who’d achieved senior VP status.
“Barney, I’m sorry—”
“I just saw your brother-in-law and your nephew at the private terminal in Philly. I was coming in from Chicago. Looked like they were getting ready to fly out. Maybe in that Gulfstream on the tarmac—had an Egyptian tail number. ‘We think our aircraft are luxurious,’ my pilot said. ‘I’d like to see the insides of that baby—’”
Natalie felt the blood drain from her face. She and Nicole had always had an ethereal connection, a sort of paranormal premonitory type of thing. And right now, she felt a stab of impending doom—
“Was my sister with them?”
“Not that I saw. Matter of fact, her husband looked my way, but didn’t acknowledge me. I didn’t care because I was in a hurry, but the little boy looked a little unsteady … like he was in a fog. He’s what … five years old now?”
Without a word, Natalie bolted out of the CEO’s office.
“Hey, what was so urgent you came barging in here?” His bellow exploded through the office door she’d left wide open.
CHAPTER ELEVEN
NICOLE AWOKE MONDAY morning at six thirty a.m. She visualized her day—rounds, a surgical procedure, patients in the office. She’d try very hard to get home by six. With the tension crackling between her and Ahmed, she wanted to make sure Alex wasn’t getting caught in the crossfire. And, she had to admit, she wasn’t doing much to soften the hostility between her and her husband. How long could that go on?
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