In 2009, a Tufts University School of Medicine professor named Dr. Daniel Carr took stock of the accomplishments of the pain program he had helped start a decade earlier.

Alumni of the master’s program included physicians, nurses, dentists, and pharmacists, he said in a post on the center’s blog. Faculty at the Pain Research, Education, and Policy program had advised policymakers and were at work on a book about pain treatment in a changing health care landscape. He also thanked the program’s donors, including the billionaire dynasty that made it possible.

“We owe much to the Sackler family, whose initial and ongoing support has been indispensable,” Carr said.

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The Sackler family built and controls the privately held Purdue Pharma, the maker of opioid painkillers including OxyContin. A STAT review of court documents, two decades of academic papers, tax forms, and funding disclosures suggests that the family and company money that went to Tufts helped to advance their interests, generating goodwill for members of the family who were praised for their philanthropy and amplifying arguments about opioids that dovetailed with their business aims.

Tufts at times opened its doors to Purdue, allowing a high-ranking executive, Dr. David Haddox — who in 2003 said OxyContin was not addictive — to lecture in the pain program, granting him the title of adjunct associate professor of public health and community medicine at a premier medical school.

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And as one of the founders of the pain program, and its current director, Carr was given a prominent platform from which to opine about opioid policy — in the classroom, in medical journals, in professional societies. Though his views have shifted, in 2001, he suggested that some patients be given strong opioids early in the course of treatment, minimized their risks, and questioned the cautiousness with which some clinicians were prescribing opioids. He has also taught continuing medical education courses for clinicians funded by Purdue.

Meanwhile, Carr’s prominence grew: In 2016, he served as president of the American Academy of Pain Medicine and moderated a panel with six governors about the opioid crisis.

Dr. Daniel Carr speaks at an event in December 2018. Screen capture via YouTube

STAT’s findings flesh out some of the allegations about Purdue’s ties to Tufts in the Massachusetts attorney general’s lawsuit against the drug maker, its executives, and members of the Sackler family. With its funding, the suit contends, “Purdue got to control research on the treatment of pain coming out of a prominent and respected institution of learning” and provided input on curriculum.

Last month, Tufts announced it had hired Donald K. Stern, a former U.S. attorney, to investigate claims that Purdue was using Tufts to promote its drugs, allegations that university President Tony Monaco called “deeply troubling.”

Aside from the Tufts allegations, the release of the unredacted Massachusetts complaint earlier this year cast a harsh glare on the alleged practices of Purdue and the Sacklers. It contends that Purdue, under the direction of some family members, misled prescribers and patients about the benefits and safety of OxyContin, ever focused on boosting prescriptions and profits while igniting an addiction crisis.

The company and the family have denied the allegations and sought to dismiss the suit. In regard to Tufts, the company said in court filings that its donations were part of its general support for educational and charitable organizations, not an attempt to control research. In a motion, lawyers for the Sackler family wrote: “The insinuation that Purdue’s funding … might have undermined the independence of some of Massachusetts’ finest institutions is not supported by any specific factual allegations of impropriety by those institutions, or by any document cited by the” lawsuit.

Carr declined an interview request. He said in a statement: “I have dedicated my medical career to advancing the understanding of the complexities of pain and its treatment. At all times, my goals in doing so have been to help patients in the most reasonable and responsible manner to receive effective pain treatment and to help medical professionals select and deliver such treatment. I have always worked toward these goals in an unbiased, objective, and patient-oriented manner, recognizing that debilitating pain is itself a serious medical condition that demands proper treatment to prevent and relieve suffering.”

He added that the business interests of biopharma companies have no influence on his views and that he would cooperate with Stern’s investigation.

Experts in pain medicine and conflicts of interest who reviewed the Tufts and Carr case at STAT’s request said it does not appear as simple as Purdue buying positive research and messaging. Instead, they said, the allegations get to the heart of knottier issues of money in medicine.

So much industry money flows to academic institutions, professional societies, and patient advocacy organizations that it’s hard to tease apart what’s a purchase of influence and what’s a marriage of convenience for groups with aligned interests or beliefs, the experts said. Disclosing the funding can help resolve questions, but it’s mostly up to individuals to police themselves about what is reported. And even when funding sources are included, it doesn’t address questions about whether companies are supporting research with a hands-off approach or trying to sway the scientific process.

“The money is so pervasive and tentacular, and we don’t even agree what’s a problem in academia,” said Michelle Mello, a professor at Stanford’s medical and law schools. “We have differences of opinion about how free we can keep ourselves from bias. Different people in academia have different tolerance for bad optics, but we’re generally left to make our own calls in these gray areas.”

People who know Carr, who earned his medical degree from Columbia in 1976, said that as a pain medicine specialist, his purview has been people in pain, and thus his priority has been keeping all options for pain treatment available.

“I think he’s a true believer,” said Dr. Jane Ballantyne, a professor of anesthesiology and pain medicine at the University of Washington and the president of Physicians for Responsible Opioid Prescribing, which advocates for limits on opioid prescriptions.

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Ballantyne formerly worked with Carr at Massachusetts General Hospital and called him a friend. Whereas her research going back to 2003 has cast doubt on the efficacy of long-term opioid use for most patients, Carr, she said, “believes that opioids do help some people with chronic pain, and therefore efforts to restrict opioids, he’s going to fight against.” (Ballantyne is a paid consultant for a law firm representing plaintiffs in litigation against Purdue and others in the opioid supply chain.)

As for the Sacklers funding Carr’s program at Tufts, Ballantyne said: “The companies — that’s how they operate. They choose a messenger who believes something that will help improve their sales.”

A shirt for sale at the Tufts University Health Sciences Bookstore in downtown Boston. Alissa Ambrose/STAT

The Sackler School of Graduate Biomedical Sciences sits in Tufts’s downtown Boston Health Sciences Campus. Three Sackler brothers who in the 1950s purchased the company that would become the modern Purdue endowed the school in the early 1980s, establishing the cornerstone in a decades-long relationship among the Sacklers, their company, and the university. The Sackler family has also given millions to other medical centers, cultural institutions, and museums, though as scrutiny of the Sacklers’ role in the opioid crisis has increased, some have said they will no longer accept donations.

In 2013, Tufts gave an honorary degree to one of the three brothers, Dr. Raymond Sackler. In praising Sackler’s global philanthropy, Monaco, the Tufts president, said then, “It would be impossible to calculate how many lives you have saved,” according to the Tufts website, which includes a biography of Sackler that does not mention Purdue. (Raymond Sackler died in 2017.) Dr. Richard Sackler, a onetime Purdue president and one of Raymond’s sons, served on an advisory board at Tufts University School of Medicine from 1999 to 2017. A Tufts spokesman said the board had no decision-making authority.

In 1999, the Sacklers made what the lawsuit calls “a more targeted gift” to establish a new master’s program at Tufts. Richard Sackler attended the Pain Research, Education, and Policy program’s launch event in Boston and “paid Tufts hundreds of thousands of dollars,” the filing says.

The program, which is a part of the medical school’s Department of Public Health and Community Medicine, was started by Carr and a medical sociologist to “instruct doctors on how to better understand the pain of their patients,” the Tufts Daily reported on Oct. 26, 1999. It has aimed to train people who work across medicine to consider and treat pain as a specific condition, an individualized experience that needs to be addressed as such.

The Massachusetts lawsuit only mentions Carr by name once, in a footnote in which it calls him an “opioid advocate.” But the pain program appears numerous times in the court filing, identified as MSPREP. Purdue, the lawsuit says, cited MSPREP as a model for how to gain sway at other medical schools and hospitals.

In a statement, Purdue said Tufts in 1997 proposed that the drug maker help fund the program, but by that time, the program’s leaders had already outlined the curriculum. The company said it stopped funding the program in 2008.

The lawsuit does not identify the Purdue employee who it says was promoted to adjunct associate professor in 2011. After being asked by STAT if it was Haddox, Tufts confirmed that he started teaching at the medical school in 2006. Haddox worked at Purdue from 1999 to October 2018, according to his LinkedIn profile, and as late as 2017, he was listing his credentials on academic papers as Purdue’s vice president of health policy and an adjunct associate professor at Tufts’ medical school.

Haddox co-authored a 1989 paper that described a 17-year-old who was taking opioids for pain and was exhibiting addiction-like behavior. But Haddox and his co-author wrote that the issue was insufficient pain treatment, and introduced the term “pseudo-addiction.” Purdue later adopted the term in its marketing materials, saying it occurred because “opioids are frequently prescribed in doses that are inadequate,” according to a slide quoted in the Massachusetts lawsuit. At a 2003 conference on addiction, Haddox said OxyContin was not addictive, according to a 2017 New Yorker story.

In a statement, Tufts spokesman Patrick Collins said that Haddox’s “teaching role was limited” and that he gave “occasional lectures in two courses that were part of the MS-PREP program.” He said Stern’s investigation would examine Haddox’s lectures.

Purdue said in a statement that Haddox “routinely disclosed” his industry affiliation and “did not promote Purdue opioid medications” in his lectures. The company said he was not paid for the lectures.

According to his LinkedIn page, Haddox is now president of Opos Consulting, which, according to its website, offers a “disease management and risk mitigation platform for the safe and compliant delivery of Chronic Opioid Therapy.” Haddox did not respond to a request for comment.

“The [industry] money is so pervasive and tentacular, and we don’t even agree what’s a problem in academia. … Different people in academia have different tolerance for bad optics.” Michelle Mello, professor at Stanford’s medical and law schools

Over two decades, Carr has expressed the view that clinicians are not effectively treating pain, in part because training programs fail to emphasize it. He describes pain relief as a human right and warns that doctors who fail to ease pain are uncompassionate.

During the early years of the pain program, when untreated pain had become a growing concern in medicine, Carr endorsed messages that bolstered the case for opioids and downplayed safety concerns. In 2001, for example, he and other pain experts met ahead of a conference and discussed how “opiophobia” was, in their view, leading to an “overestimation of the risk” of opioids and in turn the “under-treatment of pain,” according to a summary of the group’s meeting, which Carr co-wrote and was published in the Journal of Pain & Palliative Care Pharmacotherapy.

Perhaps some patients could benefit from being treated with opioids earlier instead of first trying other approaches, Carr and a co-author wrote. “Concerns about the risks of addiction and fears about possible abuse have had the most detrimental effect, and this has led in some cases to widespread suffering of patients,” they added.

Other members of the panel included an official from Janssen, a drug company that has manufactured opioids, and a researcher from the University of Wisconsin’s Pain & Policy Studies Group, which received $1.6 million in funding from Purdue from 1999 to 2010, according to a 2011 investigation by the Milwaukee Journal Sentinel. The paper does not list any conflict-of-interest disclosures.

Also, in a 2002 report from a coalition called Partners for Understanding Pain, Carr is cited as the source of a statement saying “most pain medications, including opioids, do not cause the ‘high’ associated with street drug use and rarely cause addiction.”

Partners for Understanding Pain, which is no longer active, was led by the American Chronic Pain Association, a patient advocacy group that has received funding from Purdue for years, including more than $300,000 from 2012 to 2017, according to a 2018 U.S. Senate investigation. Carr is on the ACPA’s advisory board.

In an email, Penney Cowan, the founder and CEO of ACPA, said that the funding the group has taken from Purdue and other biopharma companies has been in the form of “unrestricted educational grants, in which the funder has no input or influence on the projects they fund, or general support for operating expenses.” She added that the group had had little success in getting funding from sources other than companies that make pain treatments.

The risks of addiction and overdoses were underappreciated when OxyContin arrived on the market in 1996, but the 2001 panel and 2002 pain report that Carr participated in came after signs emerged that opioid painkillers posed risks. The U.S. attorney in Maine, for example, issued a warning in 2000 about the misuse of drugs including OxyContin, leading Purdue to form a response team.

Seven years later, Carr and other physicians wrote a review article about worldwide pain management trends that called U.S. state and federal regulations on opioids “restrictive.”

“Many physicians and patients,” they added, “harbor unrealistic anxieties about precipitating adverse side effects, believing that opioids should be reserved for the ‘end’ in cancer pain. There is also an unfounded assumption among physicians and patients that chronic opioid treatment necessarily impairs quality of life.”

The review was published the same year Purdue pleaded guilty in federal court to underplaying the risk of OxyContin addiction. It alarmed some experts, who pushed back in the most academic of ways, responding in the same journal.

Dr. Henrik Kehlet, a Danish surgeon, and Dr. Paul White, then of the University of Texas Southwestern Medical Center, wrote that the Carr review did not include any evidence that pain was going untreated.

“Although there is a clear need for improved techniques for controlling acute and chronic pain, we have serious concerns about the authors’ seemingly narrow focus on the alleged under-use of opioid analgesics and their suggestion that more liberal use of opioids can solve problems,” Kehlet and White wrote. “The recommendation by [Carr and his colleagues] that failure to alleviate pain ‘is negligent, a breach of human rights, and professional misconduct’ might well lead to increased morbidity and mortality.”

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Carr and his colleagues wrote their own reply, saying they believed that opioids were one way to manage pain and that they should be “prescribed and used in a manner that is reasonable and appropriate.”

White, who now consults for companies working on non-opioid pain treatments, described himself in a recent interview as a bit of a “radical” in his anti-opioid views. But he said his and Kehlet’s commentary was “a polite way of trying to say, ‘Hey, don’t be aggressive in promoting opioids.’ … It was a warning we tried to sound that fell on deaf ears.”

Carr has also taught at least two continuing medical education courses that were funded partly by Purdue, one in 2012 and one in 2014 — called “Caring for Outliers in a Mean Minded World” — about a growing approach to pain management that he argued excluded effective treatment for some patients. Typically, instructors of such courses receive payment directly from the medical center or medical education company sponsoring the course, not a drug company that is supporting it.

Critics of the practice, however, argue a portion of the industry money is essentially being passed through the course sponsor to the instructor, and that courses promote messaging that helps the funder.

“They are carrying water for opioid manufacturers” by teaching CMEs funded by companies, said Dr. Adriane Fugh-Berman, a Georgetown University Medical Center professor who runs PharmedOut, which examines industry influence on medicine. (Fugh-Berman is a paid expert in lawsuits against opioid manufacturers, though not the Massachusetts case.)

Purdue said that its support for the CMEs was not related to Carr being the presenter. It said the company supports CMEs as part of the Food and Drug Administration’s risk evaluation and mitigation strategy for opioid manufacturers.

Mugs for sale at the Tufts University Health Sciences Bookstore in downtown Boston. Alissa Ambrose/STAT

The way Carr talks about opioids has shifted as overdose deaths have jolted the nation’s attention. His recent papers mention the addiction crisis and he has said “an unintended consequence” of doctors’ views about pain and opioids in the 1990s is the “epidemic of diversion and misuse.” In a 2013 panel discussion, he said that opioids should not be a first-line treatment, and that he “would be suspicious of any physician who said an opioid is a first-line treatment.”

Carr has also worked on pain treatments beyond opioids. He was an executive at Javelin Pharmaceuticals, which developed a non-opioid pain treatment called Dyloject that was approved in 2014, after Javelin had been purchased by Hospira. Hospira was acquired by Pfizer in 2015.

His writing and public statements now often include critiques of the opioid prescribing guidelines for chronic pain issued in 2016 by the Centers for Disease Control and Prevention, which he calls flawed. Some of his concerns are echoed by other pain physicians, advocates, and some addiction experts, who argue that the CDC guidelines — which, for example, recommend that physicians “should avoid increasing dosage” beyond certain strengths — are being misapplied by doctors, insurers, and state agencies to justify cutting patients off opioids.

In a 2016 study, Carr and co-authors questioned the methodology of the CDC guidelines, saying that the CDC “review reached far more negative conclusions about the risk-benefit ratio for long-term opioid therapy” than prior reviews. The funding source listed on the paper is internal funding from the Department of Public Health and Community Medicine at Tufts.

Carr has reported receiving research funding from Purdue at least once, in a 2004 paper that also said the company had given an unrestricted grant to the Tufts pain program, but he has regularly reported no relevant financial disclosures. A government database that tracks industry contributions to researchers and hospitals shows Carr has not received any funding from Purdue since at least 2013 (the first year with data available).

In 2015, tax forms show, the Richard & Beth Sackler Foundation gave $50,000 to Tufts’ medical school for “program support.” And in 2017, Purdue paid Tufts Medical Center $415,000, the largest industry contribution in general funding to the center from 2013 to 2017, according to the federal database. But Collins, the Tufts University spokesman, noted that while Tufts Medical Center is the primary teaching hospital for the university’s medical school, it is a separate organization.

Some experts said disclosing industry funding to one’s institution is a gray area. The International Committee of Medical Journal Editors — a group whose reporting guidelines hundreds of journals follow — does not specifically address whether general support for a program like the Tufts pain initiative should be reported. It recommends that study authors “report all sources of revenue paid (or promised to be paid) directly to you or your institution on your behalf” for the past three years, including funding sources with relevance to a paper, not just those that directly funded it. It adds: “If there is any question, it is usually better to disclose a relationship than not to do so.”

“When somebody is critiquing efforts to rein in opioids, they should disclose the fact that their institution depends on funding from pharma,” said Dr. Roger Chou of Oregon Health and Science University, an author of the CDC guidelines. “I don’t think that’s a subtle thing.”

Carr said he was not aware of donations made by Purdue after the company’s early support for the pain program in the late 1990s and early 2000s, or of funding to Tufts programs beyond the pain initiative.

The debate over the CDC guidelines gets at broader questions about whether opioids are effective for chronic pain. Many experts believe that not only do people build up a tolerance to opioids the longer they are on them — meaning they require higher doses and face greater risks of addiction — but also that long-term use can make people more sensitive to pain.

Purdue, for its part, has promoted the CDC guidelines to prescribers, but said that ultimately, it believes that medication decisions for patients should be left to clinicians.

This story has been updated with information about Dr. Jane Ballantyne’s work as a paid consultant in opioid litigation. This information was disclosed after the story was originally published.