Acting as Watchdog on Cancer Research

In January 2002, soon after our little weekly newsletter broke a big story about troubles at a biotechnology company called ImClone Systems Inc., I got a call from a reporter from one of the major dailies. The reporter had a problem: He had a copy of The Cancer Letter in front of him, but was unable to find the material that was making ImClone’s stock drop precipitously.

“Look at the confidence interval in the middle of the first column on page four,” I suggested.

“The middle of page four?” the reporter said. “Why isn’t it in the lead?”

On some level, I sympathize with this reporter’s inadvertent criticism: Why wait until page four of a complicated, technical story before quoting an important document issued by the Food and Drug Administration (FDA)? This document turned out to be a “refusal to file” letter informing ImClone that its application for approval of its much-hyped colorectal cancer agent Erbitux was so badly flawed that it defied scientific evaluation.

Ultimately, our publication of this letter led to a congressional investigation and the continuation of a broad inquiry that came to involve the home design guru Martha Stewart, an ImClone investor and a friend of the company founder, Samuel Waksal.

Of course, I knew from the outset that this was a major story, which made it all the more important to write it in a measured tone, with a one-sentence reference to the FDA letter in the lead, a bullet-format summary on page two, and the rest in due course. In setting the stage for this revelation, I began by describing and analyzing the history of the controversy so that readers would be able to compare the text of the FDA’s letter with its characterization by the company. ImClone executives claimed that FDA was making a routine, bureaucratic request for a “train of documentation.” In reality, the agency said the problems with the clinical trials were structural, and that meant new trials would be required.

The Cancer Letter’s Approach

We assume that our readers appreciate the Talmudic complexity of cancer research, that they share our passion for finding the truth, and that they are capable of staying awake while reading a thoroughly reported, calmly paced news story. Through the years, we have earned a reputation as a watchdog publication. Yet, many of our readers are in the mainstream of cancer research: They are physicians, scientists, pharmaceutical company executives, bureaucrats, Wall Street analysts, lawyers, patient advocates, and “oncopoliticians.” And, yes, journalists read it, too.

The politics of cancer can be blinding, in part because of the tradition of promising the impossible. Had President Richard Nixon’s promises at the outset of his War on Cancer panned out, The Cancer Letter would have become historically irrelevant in 1976. Similarly, interferon, antiangiogenesis agents, and targeted drugs should have made cancer a memory, or at least a chronic disease.

Of course, scientists, when given enough adoration, are as prone as anyone to start to believe in their greatness. Meanwhile, their skeptical colleagues and onlookers have to pick their battles carefully, which means that the majority can be expected to stand by in silence, or even superficially support positions they privately disagree with. Yet, deep inside, they know that cancer is a multitude of stubborn diseases that has largely resisted both treatment and grandstanding. These people pay us $305 a year to give them the unvarnished news. We have about 1,200 individual subscribers and eight institutions—cancer centers and pharmaceutical companies—hold site licenses to distribute the newsletter to employers. They don’t need hype. They need rigorous, detailed coverage.

The Cancer Letter has been around for three decades. It was started by my father-in-law, Jerry Boyd, in 1974. Formerly a community newspaper publisher, Jerry saw a journalistic opportunity, as do my wife, Kirsten Boyd Goldberg, and I. Every week, working from the basement of our Northwest Washington home, we produce an eight-page newsletter. Often, the entire news hole is filled with just one story: about 5,000 words. If eight pages aren’t enough, we go up to 12 pages or 16. Kirsten, who is the editor and publisher, covers the National Cancer Institute and the National Institutes of Health. I cover the FDA and the pharmaceutical and biotechnology industries. Some areas of coverage—Capitol Hill and patient advocacy—bounce between us.

As owners of The Cancer Letter, we have no targets for growth of our business. If, during some years, our gross revenues or profitability remain flat, or if we lose a subscriber or two as a result of publishing a hard-hitting story, we don’t panic. The majority of our stories would be likely to put an average reader to sleep. Sometimes, when I try to interest colleagues in picking up stories I consider important, I hear unsuccessfully suppressed yawns. Reporters who call us for quick answers to complicated questions tend to be disappointed. Like it or not, the cancer field is built on nuance.

We write about the gears of the system of research and drug development. How are scientific programs selected to receive funds? How are drugs selected for clinical trials? What are the criteria used in drug approval? Are they scientifically valid?

The ImClone Story

Consider the ImClone story. Our opportunity to write about that company was brief. The ImClone lead agent Erbitux was gathering a following among oncologists, patients, Wall Street analysts, and business and science writers. The name of the company president and chief executive, Sam Waksal, was popping up in society pages. Bristol-Myers Squibb paid about two billion dollars for a stake in Erbitux.

Yet, to us, preclinical development and early clinical trials usually fall outside the boundaries of coverage. Until a drug is subjected to rigorous review, we ignore it. It’s not that we were missing the boat on ImClone; we were simply letting the boat drift by in the fog. Before approval by FDA, a drug falls into a regulatory no-man’s land, which means that it can be hyped with relative impunity. FDA authority begins at the time of approval.

While drugs are under review, the agency has no authority to stop companies from making unsubstantiated claims. By law, the FDA is precluded from contacting the Securities and Exchange Commission to say that a company is making unsubstantiated claims and talking up the value of its stock.

As soon as rigorous review of an agent begins, The Cancer Letter becomes intensely interested in both how the agent is measuring up and in the criteria used in its evaluation. Less than a week after the FDA notified ImClone that its application was unintelligible, I obtained the agency’s letter, quoting much of its text in two consecutive news stories, which we published over two weeks. While the ImClone scandal exploded on financial pages of the daily newspapers, I paid little attention to the allegations of insider trading and focused on the structure of the clinical trials that the company conducted and on the proprietary protocols that were used.

With my limited understanding of clinical trials, which I picked up entirely on the job, I could see that ImClone’s trail was unclear in defining the eligibility criteria. Also, the trial seemed to have been altered from a shot-in-the-dark experiment conducted for generating hypotheses to a “registration trial” intended to support approval by the FDA. The result was about as informative as the score from a game that has no clear criteria for selection of players and where the sport changes at halftime from football to soccer to satisfy the wishes of the referee.

As I stared at the ImClone protocol, I knew that journalistic analysis would take me only so far. To make the story definitive, I called three acknowledged experts and asked them to review the protocol. Rather than using a few quotes, I asked each of them to write about 650 words. We published the critiques in their entirety, with the reviewers’ names included. Tongue-in-cheek, we call this technique “investigation by peer review.” It’s an excellent method for presenting technical information to a sophisticated readership.

While the three reviews and the story that accompanied them were excessive for a general audience, their publication allowed The Cancer Letter to once again alter the level of discussion of the ImClone controversy. In turn, our stories helped to inform the Congressional investigation and prompted stories in The New York Times, on National Public Radio, and CNN.

With the ImClone story, our watchdog publication, through specialized coverage, was able to communicate complicated scientific analysis to a broader audience by getting this information to reporters in the mainstream media.

Paul Goldberg, along with his wife, Kirsten Boyd Goldberg, produce a weekly watchdog newsletter, “The Cancer Letter,” which won the 2002 Robert D.G. Lewis Award of the Washington chapter of the Society of Professional Journalists.