by Harry Stein
The Board stayed behind closed doors for no more than fifteen minutes, presumably discussing the protocol in very general terms. Then the three junior associates were invited to join them.
“Well,” began the Department of Medicine’s Herlihy, chairing the meeting from the head of the conference table, “right off the bat, I must say a lot of solid thinking went into this idea.” He paused, waiting for those pleasant words to register. “However, as you know, we are able to approve only a very small number of protocol plans. Only those that meet the strictest criteria, not just for scientific merit but ethical accountability.” He nodded their way. “Now, I gather you, Dr. Logan, are speaking on behalf of the team?”
“Yessir.”
Logan rose and took a seat in the empty chair at the opposite end of the table. He smiled. “Ladies and gentlemen, on behalf of my colleagues and myself, I want to thank you for your time and consideration. I’m sure I have little to tell you today that you don’t already know. We are proposing a Phase Two pilot trial of the compound known as Compound J for metastatic breast cancer. In order for the trial to have appropriate statistical power, we feel we need to accrue forty patients over the next twelve months.…”
And he began to lead them through the case for Compound J; emphasizing, particularly to the lay people on the Board, the significance of the various reports of the drug’s activity spanning decades and great distances. “I will not pretend to you that we know more about this drug than we do,” he wound up, with what he hoped was just the right note of deference and candor. “But what we have already observed is compelling: clear evidence that this drug is capable of binding growth factors to their cell-surface receptors. The truly astonishing thing is that, as long as this drug has been around, it has never undergone a rigorous and closely monitored clinical trial for activity against this disease. That is a situation that, with your help, we now hope to rectify. Thank you.”
And nodding once again to the board members, he sat down.
“What about your Informed Consent Document?”
It was Winston, the patient care rep.
“Pardon?”
“Is it your position that this document displays sensitivity to the needs of the women you would enlist for such a trial? That it serves them well?”
Logan hesitated. What could she be getting at? “We think the Informed Consent Document does what it is supposed to do,” he offered finally. “Which is present all the most likely problematic scenarios.”
“Oh, does it? Dr. Logan. As you’ve acknowledged yourself, this is a very toxic drug. I am not a physician, but I have it on the very best authority that you do not come close to covering all likely eventualities. For example, you never even address the possibility of cerebral hemorrhage. Or heart attack.”
In fact, the woman was only confirming her ignorance—of all the possible calamitous effects of Compound J, the chances these were among them were infinitesimal. Still, Logan worried she might be scoring points with the others; following Shein’s instructions to the letter, in the final draft of the proposal, they had passed lightly over the unsettling matter of side effects. He was suddenly aware that the room seemed to be overheated.
“Ms. Winston, I really don’t think the possibilities you raise merit serious consideration.”
“The point, Doctor,” spoke up the bioethicist, “is that some of us feel that a less than thorough investigation has been made as to the downside of this drug. Some of us feel that rather strongly.”
There was a superior note to the guy’s tone that drove Logan crazy. What the hell did he, who’d never in his life so much as touched a patient, know about the thoroughness of their investigation? He felt like diving across the table and taking him by the throat.
“Well,” he said evenly, “all I can tell you is that we’ve spent a great deal of time on this. Certainly, if we’d been completely exhaustive, other possible eventualities might have been listed. I acknowledge that. But it would have been pure speculation. That’s the point: we need to know more about this drug.”
“I see”—Winston again—“and you’re planning to use these patients as human guinea pigs.”
“I didn’t say that. That’s not fair.” He stopped, collected himself. “Isn’t it fair to say there’s a certain degree of uncertainty in a test of any new compound?”
He looked hopefully at the medical personnel around the table: the surgeon, the radiologist, the nurse. Surely, they were with him on this.
But no one gave a word of support.
“Dr. Logan,” said Winston, her voice taking on a dangerously hard edge, “we are not raising these questions in a vacuum. We must all be aware of the fact that the public’s confidence in breast cancer trials has been badly shaken in recent years by doctors more concerned with their own reputations than with the well-being of patients. Frankly, in your case, we would find such questions less troubling if certain other aspects of your history had not been brought to our attention.”
He tried to smile. “Ms. Winston, I really have no idea what you mean.”
“Are you aware of a patient at the ACF named Rochelle Boudin?”
Logan felt his stomach rising, the beginnings of nausea. He stole a glance at Lennox, but she was looking down, making notes on a legal pad. “Yes, I’ve been one of the doctors who’s helped care for Rochelle Boudin.”
“I gather from that response that you feel your care has been adequate.”
“Yes. I would say very much so. She appears to be in complete remission from her disease.”
“It is fair to say that the patient does not share that assessment. I have interviewed Ms. Boudin personally.” She held aloft a notebook in grim triumph. “Perhaps you’d be interested in some of what she has to say.” She opened the book. “She describes you as—this is a quote—’ the most insensitive doctor I’ve been exposed to at the ACF.’ She says you are chronically indifferent to her needs. She says—again I quote—she feels ‘you look for ways to take advantage’ of her, and she feels you rarely if ever tell her the full truth.” She closed the notebook. “I could go on.”
Never in his life had Logan been faced with such a thing. By temperament, he simply was not equipped to deal with it. “I could probably say a few things about Rochelle Boudin too,” he offered lamely.
“She is not the one asking for authority to conduct a protocol.”
“So,” he added, “could almost everyone at this place who’s had to deal with her.” He looked toward Lennox. “I think Nurse Lennox might confirm that.”
Lennox looked up from her pad, her face going red. “Sometimes she can be difficult.”
“You are aware that Ms. Boudin is a patient on one of Dr. Larsen’s protocols?”
“I am aware of that, yes.”
“Well, I must tell you that Dr. Larsen fully shares her view of the situation. Are you now going to tell us that Dr. Larsen is incompetent to make such a judgment?”
So that was it? Larsen! Abruptly, Logan was overwhelmed by a sense of helplessness. It was over. There was no way to fight this.
“Ms. Winston, I don’t know what you expect me to say. I’ve done my very best with Rochelle Boudin, as I have with all my patients. I—”
“Look,” he was interrupted, “this is absurd. We’re talking about the wrong things here.”
The voice was unmistakable, but Logan jerked around to see for himself. Shein was standing just inside the door. There was no way to know how long he’d been in the room.
“You want to talk about the Informed Consent Document?” he picked up. “Fine, blame me. I’m the one who told ’em to make it short and sweet. But, Christ, you don’t throw out the goddamn baby with the bathwater!”
Shein’s intrusion, as everyone in the room knew, was highly unorthodox. But they also knew—and Shein better than anyone else—that no one was about to stop him. Now he moved to the table and stood beside Logan.
“What the hell are we really here for?” he picked up. “I
don’t mean just in this room but at this institution. We have a major problem in this country with cancer, and an especially major one with breast cancer, okay? And don’t think we’re making such strides against this disease. The mortality rate is the same as it was twenty years ago. Nobody wants it that way. But the bottom line is, we still don’t know what the hell is going on.
“Now, our friends here have come up with an idea that seems—that may—attack this thing at its roots. In my considered view, based on twenty years in the business, this is a novel and rational idea that has been thought through very carefully. And as such it represents a not irrational hope for women who otherwise have no hope.”
Pausing to look around the table, he drove the point home. “So I’m asking you now to put aside the politics. Put aside the bullshit and the arguments about things that don’t matter. Because we all know that no one who’s terminally ill gives a damn about anything but trying to get well. Those people have only one question. They look their doctor in the eye and say, ‘Should I go on this protocol?’ And if the doctor believes in his or her heart it’s the right thing, then that patient will go on that protocol. That’s reality. It may not fit the textbook theories, but that’s the way it is.”
He paused. “And I’ll tell you one other thing. If, God forbid, it were my wife, I’d sure as hell want her on this protocol—even if I don’t know every one of the goddamned toxicities.”
It took the Review Board, meeting in private, little more than a half hour to reach its decision. The Compound J team was granted a modified protocol—a smaller and more closely monitored version of the one they’d proposed.
The note on the bottle of champagne that arrived at Seth Shein’s door that evening didn’t even try to be clever. The words, in Logan’s hand, appeared above the three signatures: All the gratitude we can ever express will never be enough.
According to the guidelines imposed by the Review Board, the Compound J team had to have a “hit”—a demonstrably positive result—within the first fifteen patients. That meant tumor mass had to be reduced by at least fifty percent.
It was a daunting task. Still, for days after the meeting, Logan was flying. Finally, he and the others had their opportunity—and if it came in a slightly revised package, this is what they’d bargained for all along: a shot at making the case that the drug was both active and relatively safe.
Already, they knew they were most vulnerable on the toxicity issue. If patients failed to respond to the drug, that would be taken as unfortunate, an unhappy outcome to a worthy effort. But if the drug made patients dramatically sicker, or, God forbid, started killing them, it would be a catastrophe—nearly as much for the doctors involved as for the patients. Since before Hippocrates, medical science has dictated that the life of a patient is a sacred trust. To be perceived as abusing that trust, even with the best of intentions, is to raise questions about one’s very fitness for the profession.
Going in, they were determined to take every possible precaution to avoid such a disaster.
That placed even greater than normal importance on their most immediate order of business, putting together a patient roster. “It’s easy,” as Shein pointed out, “to kill a good drug with a bad trial.” And the easiest way to screw up a trial is to stock it with patients whose chances of doing well are already compromised going in.
Unfortunately, almost every potential candidate for this protocol would likely fall into that category since, upon diagnosis, they’d have been treated by either chemotherapy or radiation; and it is a given that anyone who’s already proven resistant to one therapy is likely to be resistant to others.
Thus, the best they could reasonably hope to do was locate fifteen women whose exposure to such treatments had, for whatever reason, been minimal.
The process of accruing protocol candidates was made far more cumbersome by Larsen’s refusal to grant the Compound J team a private office. This meant they’d be unable to field incoming calls directly, having to rely on their beepers to stay abreast of those that held promise; and make outgoing calls from the phone bank in the communal room—half work-space, half lounge—they’d shared with other first-year fellows from the start.
But Larsen could not prevent those calls from coming. For he could not deny them access to the ACF’s Community Outreach System—its link to the world of oncology beyond its borders. Like every other protocol being conducted at the ACF, a summary of the Compound J test was duly recorded in the system, available in printout to any physician calling the Foundation hotline.
The description of the protocol was followed by an appeal for likely candidates. At the urging of Reston, the wordsmith among the trio, this last they made short and sweet: This test requires a small pool of women with metastatic breast cancer; minimum performance status of seventy percent; must have no history of bleeding disorder or heart attack. Contact: Dr. Daniel Logan, Dept. of Medicine, ACF. 1-800-555-2002.
“It’s a trick I learned writing personal ads,” explained Reston, smirking. “Trust me, the more exclusive you make yourself sound, the more bites you’ll get.”
In fact, they expected a rush of calls—and so were concerned when the first several days produced only one inquiry. Alerted to the call via his beeper while on his rounds, Logan managed to make it down to the junior associates’ room within ten minutes to return it.
He found himself talking to a physician named Gillette, in Brownsville, Texas. From the sound of his voice and his courtly manner, he seemed to be well up in years. Gillette’s patient was a Mrs. Mary Brady.
“She’s just a lovely lady,” he explained, in a gentle drawl, “it’s just a shame what’s happening to her.”
Never having fielded such a call before, Logan wasn’t quite sure of the etiquette. How hard to push for the vital information he needed? How encouraging to sound about the protocol itself? “I’m very sorry to hear that,” he said. “Can you tell me a little something about the case?”
“Well, she’s forty-eight years old. Got two teenage boys that play on the football team—nice boys, not the sort that cause anyone trouble. We just want to do whatever we can to help her.”
“Uh-huh.”
“And this morning I just happened to dial up the ACF and I noticed this new protocol you’ve got going.”
“Yes. I see.”
“Can you tell me a little something about it?”
How, Logan wondered, had he suddenly become the interviewee? “Uh, well, it involves a drug called Compound J. We have reason to hope it will show activity against metastatic breast cancer. But I must stress this is a highly experimental treatment. We’re actually just getting started.”
“Well, frankly, I’m at the end of my rope down here. We’ve been through just about everything with this woman. At this point I don’t know what to do with her.”
“Can you tell me how long ago she was diagnosed?”
“Certainly … I’ve got the records right here in front of me.” He paused. “Mary first found the lump fourteen years ago—that would make her thirty-four. I recall it was during her second pregnancy.”
“Uh-huh.”
“So we waited. But after the birth, she had a modified radical. She got an axillary lymph node dissection at the same time.”
“But it recurred …?”
“I’m afraid so—five years ago. Since then we’ve been trying to handle it with standard chemotherapeutic agents. But, as I say, things are looking pretty desperate now.”
Logan had already heard more than he needed. Still, he didn’t quite know how to break the bad news to the man on the other end. “I presume the tumor is estrogen-receptor negative,” he pressed on, hoping the other would pick up the hint. The absence of the protein necessary to bind estrogen to cells is a devastating prognostic factor in such cases.
“Yes, I’m afraid so.” Dr. Gillette paused. “We even tried giving her taxol, that stuff from Pacific yew tree bark. Her family insisted, after the newspapers made such a f
uss over it and all. But it didn’t do a bit of good.”
“I’m sorry. That’s unfortunate.”
“So, Dr. Logan, what’s the next step? Would you like me to send you her records?”
Logan hesitated. “Listen, Dr. Gillette, I’m afraid the truth is we’re not going to be able to help her.” He explained about the need for patients with a comparatively clear treatment history.
“Please, Doctor,” came the reply, now almost a plea, “I’m not going to tell you how to run your business. But I’m sure there’s more you can do for her up there than we can here. You have fourteen other spots, what would you have to lose? What would she have to lose?”
“I’m truly sorry” was all he could say. “Please understand that we must include only patients who fit the profile. To begin doing otherwise would put the entire test at risk.”
The call put Logan in a funk for the rest of the day. This was one of the aspects of the process to which he’d frankly given almost no thought: the degree of ruthlessness the accrual process demanded of him. Almost as bad, he’d be regularly reminded of the fact by other doctors, decent men and women, earnest and uncomprehending, pleading on their patients’ behalf.
Over the next few weeks, as the calls slowly began to pick up, Logan noted a strikingly high percentage of those doctors making referrals to the protocol turned out to be in their sixties and seventies; people whose sense of values seemed rooted in a time as alien to most at the ACF as the nineteenth century.
Because, finally, for a doctor to refer a patient to a trial such as this was not merely a leap of faith—an acknowledgment that an untested treatment was likely of more value than anything he could offer—but an act of self-denial. It meant punting away easy money—in those cases where the patient was still in the relatively early stages of the disease, potentially a very great deal of it.
As the days passed, promising candidates got no easier to come by. Three weeks into the process, only a handful of women were being closely considered, their written records, X rays, and pathology slides having arrived for study; but not a single one had yet been accepted into the protocol.
