Yuyun Lusiyani
When Dr. Craig Towers, a high-risk obstetrician, relocated to Knoxville, Tennessee, in 2010, he was confronted with a public health emergency of a scale he had never before witnessed. Having practiced for a quarter-century in California and Wisconsin, Towers found himself treating an alarming number of pregnant women struggling with painkiller addiction and, consequently, delivering an unprecedented volume of newborns suffering from severe opioid withdrawal symptoms, medically known as Neonatal Abstinence Syndrome (NAS) or Neonatal Opioid Withdrawal Syndrome (NOWS). These infants, often inconsolable and experiencing tremors, seizures, and other distressing symptoms, required weeks of intensive, specialized care, becoming poignant symbols of the region’s devastating opioid epidemic. "We were inundated," Towers later recounted to the Knoxville News Sentinel, describing the overwhelming challenge.
In the face of this profound crisis, Towers identified not only an urgent clinical need but also a critical research opportunity. Traditional medical consensus had long dictated that attempting to detoxify a pregnant patient from opioids was unsafe, primarily due to the potential for severe fetal distress, including physical trauma or even miscarriage. Instead, the prevailing standard of care involved prescribing legal replacement opiates such as methadone or buprenorphine. These medications, while controlling cravings and significantly reducing the risk of overdose, could still result in newborns experiencing withdrawal symptoms, but the medical community reasoned that treating these symptoms in a controlled environment was preferable to the potentially fatal risks associated with unsupervised withdrawal or continued illicit drug use.
Towers, who initially joined the University of Tennessee Medical Center’s high-risk pregnancy clinic before becoming a medical school faculty member, began to critically re-evaluate this long-held approach. He embarked on a study, primarily involving his own patients, who chose to cease their opioid dependency, including those on replacement therapies. Over time, he amassed data on more than 300 women, forming the basis of what he believed would be a paradigm-shifting revelation.
A Promising Breakthrough Amidst a Crisis
Towers’ preliminary findings suggested that detoxification during pregnancy was considerably less harmful to the fetus than previously believed. His research, if validated, had the potential to revolutionize how pregnant individuals with opioid use disorder were treated. Clinics across Tennessee, from Johnson City to Jellico and Sevierville, and even as far as Daytona Beach, Florida, began to adopt protocols inspired by his emerging work. His efforts garnered significant recognition; the News Sentinel hailed him as a "Health Care Hero," and CNN’s chief medical correspondent, Dr. Sanjay Gupta, interviewed him, describing babies born without withdrawal symptoms as "miracles." In 2019, the University of Tennessee Medical School acknowledged his contributions with additional funding, commending his "many research efforts and leadership that has resulted in national recognition." Months before the eventual publication of his seminal study, Towers confidently declared at a university science forum, "I think it’s going to revolutionize what we do."
The study, titled "Use of naltrexone in treating opioid use disorder in pregnancy," was published in 2020 in the American Journal of Obstetrics and Gynecology (AJOG). It was the largest of its kind, involving 230 participants, 121 of whom received a daily dose of naltrexone. Naltrexone is distinct from methadone or buprenorphine as it is not an opioid agonist; instead, it acts as an opioid antagonist, blocking the euphoric effects of opioids and thereby discouraging their use. Towers’ study reported that naltrexone was effective in maintaining most patients in an opioid-free state throughout their pregnancies.
However, shortly after its publication, and despite the preceding acclaim, Towers abruptly withdrew from his research endeavors.
Expert Scrutiny and Mounting Concerns
The published study immediately captured the attention of addiction treatment specialists, many of whom expressed skepticism regarding its findings. Naltrexone, in numerous other major studies involving non-pregnant populations, had demonstrated generally lackluster results, with relapse rates averaging 72%, according to a systematic review of 13 studies. The stark contrast between these established outcomes and Towers’ reported success prompted serious questions.
A group of eight specialists in addiction and pregnancy, including Dr. Mishka Terplan, a practicing OB-GYN board-certified in addiction medicine who had contributed to federal and professional guidelines for opioid use treatment during pregnancy, began to share their concerns. In July 2020, they formally drafted a letter to the University of Tennessee, expressing profound apprehension. "Dr. Towers’ work has been impactful, especially in TN," Terplan wrote, "and I am concerned that each day the article(s) is out there, potential harm to a vulnerable population accumulates through both ethically suspect clinical care and consequently misguided public health." Two of these specialists later spoke with ProPublica, choosing to remain anonymous due to the sensitive nature of the allegations.
University Audit Uncovers "Serious Noncompliance"
Concurrently with the rising external skepticism, an internal audit by the University of Tennessee had already been underway, and its findings were damning. The audit report, finalized in February 2020, identified "major problems" with Towers’ research. Among the most critical findings was that Towers had failed to secure the necessary university approval for the study from the Institutional Review Board (IRB) – panels of scientists and compliance specialists mandated to protect the rights and welfare of human participants in research. This omission alone constitutes a serious violation of research ethics.
Furthermore, the audit reported that Towers provided "inaccurate and/or unverifiable, contradictory source documentation" for a key component of the study and failed to furnish requested research databases or data analyses. Auditors also could not ascertain the extent to which confidential patient health information was adequately protected. These findings painted a picture of deeply flawed research methodology and oversight.
The Journal’s Delayed and Limited Response
Despite these grave concerns raised by both external experts and the university itself, the American Journal of Obstetrics and Gynecology (AJOG) remained publicly silent for three years. When the journal finally acted in 2023, its response was minimal: a 78-word correction. The correction stated that the study had been "improperly listed as a ‘prospective’ cohort study – which is not the case." It clarified, "We did a retrospective analysis of prospectively collected data."
The distinction between prospective and retrospective studies is fundamental in research. Prospective studies involve following patients in real time, meticulously collecting data as events unfold, offering greater control and insight into factors like patient attrition and evolving health conditions. Retrospective studies, conversely, analyze existing medical records. Towers himself had previously touted the naltrexone study’s prospective design as an advancement over his earlier retrospective work. Experts consulted by ProPublica unanimously deemed this misrepresentation of methodology a significant breach of scientific integrity, far more substantial than a minor error.
ProPublica shared Towers’ study, the university’s audit, and the journal’s correction with five experts in research ethics and substance abuse during pregnancy. All expressed profound concerns about Towers’ conduct as a researcher and criticized the journal’s response as insufficient to address the issues unearthed by the university. Elsevier, the publisher of AJOG, however, defended its actions, stating, "We uphold the highest standards of rigor and ethics in our publishing to protect the quality and integrity of research."
Patient Experiences and Ethical Dilemmas
Media coverage prior to the controversy often portrayed Dr. Towers as a compassionate physician deeply committed to his patients, frequently highlighting the challenging circumstances that led them to addiction. He expressed that the women’s desire for a better future for their babies inspired his investigation into prenatal detox.
However, the ethical implications of the research, particularly concerning informed consent, became a central point of contention. Katie Carringer, a former patient of Dr. Towers, shared her experience with ProPublica. In 2018, Carringer, then six weeks pregnant and working as an administrative assistant at a drug rehab facility, sought Towers’ care. She had a history of heroin addiction but was not actively using drugs at the time and felt confident in her sobriety. Her primary reasons for seeking a high-risk obstetrician were to manage anxiety and depression, and she had ceased taking her prescribed Paxil and Remeron out of concern for the fetus.
Carringer was surprised when Towers recommended naltrexone at her second appointment, as her professional experience indicated the drug was typically for individuals in the early, craving-intensive stages of recovery. "With me being clean so long, it didn’t even make sense," she stated. Her medical records confirmed a history of sobriety during previous pregnancies and completion of an inpatient drug treatment program two years prior, with only two brief relapses since. While Towers’ records noted her interest in naltrexone, Carringer denied this to ProPublica, asserting she felt pressured to take it. She stopped after the first dose due to severe nausea, a side effect her records confirm.
This experience resonated with the concerns raised by Dr. Terplan and the other specialists in their letter to the University of Tennessee. They questioned whether patients fully understood the experimental nature of naltrexone treatment during pregnancy and if proper informed consent had been obtained. "This uncertainty leads us to question whether ethical standards that promote and ensure respect for human subjects and protect their health and rights were followed," their letter stated. Dr. Robert Klitzman, a bioethics expert at Columbia University, emphasized the critical importance of informed consent, noting, "You need to explain to people that there may be additional risk."
Towers, in his defense, maintained that concerns about consent were baseless. He claimed all study participants received a "notice of research" and consented to participation, understanding that their de-identified data would be prospectively collected. "I am not aware of any patient that felt pressured to participate," he wrote, adding that he always presented patients with the risks and benefits of each treatment course. However, critics like Klitzman argue that researchers must be able to provide specific details about actual study participants, not merely a blanket statement about all clinic patients.
Further questions arose regarding the reported health outcomes. Hendrée Jones, a University of North Carolina researcher and signatory to the letter, found it unusual that the study reported only minor health problems, such as nausea and headache, among the mothers, with no serious medical events, especially given their history of opioid addiction. "That made my hair on the back of my neck stand up," Jones remarked, indicating a statistical anomaly that raised suspicion. Towers countered that critics were not privy to his clinical operations and that his study captured all patient outcomes, including vital signs, preterm labor, spontaneous abortion, stillbirth, and fetal stress.
Towers’ Retirement and the Pursuit of Retraction
In February 2020, approximately two weeks after the university audit commenced, Towers retired from his faculty position. Months later, he also ceased clinical practice, citing health and family reasons. The audit’s completion coincided with a determination letter from the chair of the IRB, which stated that the board voted to suspend all of Towers’ open studies for safety reviews and to file a report with the federal Office for Human Research Protections, characterizing the audit’s findings as "serious noncompliance." Towers voluntarily closed all research projects upon his retirement, but he disputes the IRB’s findings, arguing that the board did not adequately engage him or his co-authors to present their perspective.
Following his resignation, Towers contacted AJOG, providing IRB approval letters he asserted validated his study. "I am sorry you have to spend time with this controversy," he wrote to the journal. However, the university audit had already concluded that these cited IRB approvals did not pertain to the specific naltrexone study in question.
The University of Tennessee also communicated directly with the journal. In an email acknowledging the specialists’ concerns, the university’s research director confirmed that UT had "requested the paper be retracted from the journal, but as yet no action has been taken by the journal."
The Broader Implications: Scientific Integrity and Journal Accountability
Retractions are a rare but significant event in scientific publishing, occurring in less than 1 in 2,500 published studies. They carry immense weight, capable of damaging a researcher’s reputation and undermining a journal’s credibility. While universities, like the University of Tennessee, can investigate misconduct and request retractions, the ultimate decision rests with journal editors. Ivan Oransky, co-founder of Retraction Watch, a platform dedicated to tracking scientific misconduct, highlighted that journals sometimes fail to retract studies even after university requests, creating a situation where "the fox is guarding the henhouse." Oransky advocates for greater public accessibility of research misconduct reports, calling them "the basis for understanding whether something is reliable or not, and what went wrong."
During the years that AJOG deliberated its response, Towers’ study continued to circulate and be cited dozens of times in other research, potentially influencing clinical practice and encouraging more doctors to prescribe naltrexone to pregnant women. Towers steadfastly defends naltrexone as a viable treatment, asserting, "I believe it is crucial in medicine to revisit old assumptions and consider all options." He maintains that detox offers a solution "in the interest of advancing medicine and helping patients in a region where drug abuse is a longstanding issue."
Clinical experiences, however, have been mixed. Dr. Geogy Thomas, medical director of Dayspring Health in East Tennessee, expressed gratitude, stating, "Our community is indebted to Dr. Towers and his research on substance abuse in pregnancy. He courageously challenged the status quo… and ushered in a new way of caring for a high-risk group of patients." Conversely, Dr. Cathleen Suto, an obstetrician who worked at a clinic inspired by Towers’ research, found that detox was not consistently effective, with many patients unable to complete the weaning process, often dropping out of care. As quoted in the book "Prosecuting Poverty, Criminalizing Care," Suto remarked, "Detox would be a great answer. The problem is that my patients were not successful at doing it."
The journal’s 2023 correction, clarifying the study’s methodological classification from "prospective" to "retrospective analysis of prospectively collected data," is viewed by Towers as vindication. "AJOG would not keep a study in print if they did not believe it was IRB-approved after their review," he asserted. However, the specialists who wrote to the university, all experienced researchers themselves, consider misrepresenting methodology a fundamental breach of scientific integrity. "If it was not prospective but presented as such, it would have violated standards of reporting of scientific research," their letter emphasized.
In response to expert claims that the problems identified by the audit were more profound than the correction suggested, Elsevier maintained that "Based on the information available at the time, the Journal determined that a correction was appropriate to clarify the description of the study." Yet, Hendrée Jones, a signatory to the initial letter, criticized the journal for failing its duty to uphold higher research standards. "When you make a mistake, you own up to that mistake and you fix it," she stated, lamenting that "that paper is out there, and continues to be cited, and I see it." The ongoing presence and citation of a study facing such significant allegations underscore the critical need for robust mechanisms to ensure research integrity and journal accountability in protecting patient safety and public trust.
Nila Kartika Wati
Joko Widodo
admin
Lina Irawan