Academia, industry and the slow adoption of new treatments

Abstract

Klein et al. discuss the academia-pharma industry gap and its impact on patient care, arguing that the severing of academic collaboration with industry has caused a drop in academic participation in clinical trials, delayed adoption of new treatments, and harmed patients. They suggest a patient-centred approach to academia-industry relations.

The unintended consequence of academia's ‘divorce’ from the pharmaceutical industry, driven by ethical concerns, has been a significant delay in people’s access to vital new treatments.

Divorces are messy things, as they typically result in a loss for everyone. This has been the unintended outcome of academia’s divorce from the pharmaceutical industry over the last 15 years. The party most injured in this are people suffering from diseases.

Over 20 years ago, the pharmaceutical industry often offered lavish entertainment to prescribers. These were rightly seen as potential inducements to prescribe the touted treatment, resulting eventually in significant fines imposed by the US Food and Drug Administration (FDA) on US pharmaceutical companies. Consequently, these practices were largely phased out by the late 2000s and replaced by the industry’s own ethics guidelines.¹ What remained were educational events focused on branded treatment with FDA-approved content. Then, in 2010, the Sunshine Act took effect, mandating public disclosure of any payments or rewards made by healthcare companies to healthcare providers. Europe has seen similar changes, with increasing restrictions on the relationships between the pharmaceutical sector and academic institutions, particularly for clinical academics working in teaching hospitals.

Academic institutions began to distance themselves from the pharmaceutical industry, fearing that faculty rewards from industry-sponsored events, such as promotional talks or advisory boards, could lead to prescribing bias. Over 10 years ago, this concern intensified; the concept emerged that any industry contact may create bias and be detrimental. Industry representatives were banned from the campuses of many US medical schools, and faculty were discouraged or even prohibited from most interactions with industry, including non-Continuing Medical Education activities. Following the Sunshine Act, private practices largely mirrored academia, instituting similar no-contact policies. This created a prominent separation between medical academia and, to a lesser extent, clinical medicine across the US and Europe from the pharmaceutical sector. This shift aimed to avert a conflict of interest that could impact care, safeguard independent judgment, transcend financial considerations and maintain ethical purity.

This attitude needs reappraisal. Healthcare providers and administrators often overlook a crucial internal division: the separation between Research and Development and commercial promotion. The Research and Development branch conducts preclinical and clinical research, data analysis and interacts closely with regulatory agencies such as the European Medicines Agency and FDA at every stage. The commercial branch only steps in to promote drugs after they have been approved, and regulatory agencies also supervise this promotion. Companies operate with strict rules that mandate separate teams, reporting lines, and firewall policies to limit cross-functional influence between Research and Development and commercial operations. Regulators oversee this separation, ensuring that profit motives do not influence scientific decisions and that drugs are only promoted after they have been thoroughly reviewed and approved. The goal is to protect users’ safety and preserve the integrity of medical research.

Boundaries between research functions and commercial teams have increased transparency. Clinical trials are now registered on ClinicalTrials.gov, with open sharing of protocols and analysis plans, and public access to results regardless of outcome, reducing selective reporting and publication bias. The ethical oversight of trials has improved, with enhanced informed consent processes, independent ethics committees and increased involvement of patient advocacy, all of which have strengthened individual rights and safety.

Ethical purity comes at a cost: individuals may experience delayed or absent access to new treatments. Academia might lead in education and practice, but it is the industry that develops the majority of new therapies. Our subspecialty is epilepsy, affecting up to 1% of the global population. Approximately one-third of patients with epilepsy have drug-resistant epilepsy (DRE)—approximately 1 million patients in the USA. Since 1990, the FDA has approved 20 new antiseizure medications (ASMs), all developed by the industry. While academia sometimes makes initial discoveries, it does not undertake the extensive and costly clinical development necessary for regulatory approval; the industry does. Companies rely on collaboration with clinical centres to enrol people in trials for new treatments. Academia’s withdrawal from this sector has resulted in dwindling participation by academic centres in these trials. This, in turn, means that academicians often lack first-hand experience with recently launched therapies, which ultimately impacts patient access and knowledge.

We have seen a worrying trend where promising new drugs have been underused, and we believe that their use has suffered partly because of this withdrawal. The most recently approved ASM is cenobamate, which was FDA-approved in 2019. Just 20 years ago, academic epilepsy centres were leading participants in pivotal trials and were among the first to adopt new treatments. By contrast, in the cenobamate pivotal trials, only a third of US centres were academic.² Cenobamate appears to be more effective in DRE than other ASMs approved since 1990.³ Two years after the launch of cenobamate, physicians at only about half of medical school hospitals had used it.² Academic physicians lead the adoption of new treatments. If they do not use a treatment, neither does the medical community. The slow adoption of new therapies can cause unnecessary suffering if the new treatment offers advantages over existing treatments. It took almost 4 years after the US launch for 100 000 people to be treated worldwide—approximately 10% of the 1 million adults with focal DRE, conservatively estimated to live in the USA, Canada and Europe, where cenobamate is approved.^4,5

The situation is similar for fenfluramine, which appears to be effective for treating seizures in Dravet syndrome. It is especially effective in reducing hazardous convulsive seizures. These life-threatening conditions respond poorly to previous ASMs. In the 24 months after fenfluramine’s 2020 US launch, fewer than 1000 of the approximately 20 000 people with Dravet syndrome were treated with it.⁶

Treatment adoption was similarly slow for three prior ASMs: brivaracetam (2016), perampanel (2013) and eslicarbazepine (2012). However, the seizure-free rates in clinical trials of those drugs did not differ markedly from those of earlier ASMs. The rate of adoption was significantly higher earlier, for example, with lacosamide (2009).

The sluggish uptake of cenobamate, fenfluramine and potentially future ASMs by academic centres comes at a steep price for people with epilepsy. While physicians are understandably cautious about new treatments due to the possibility of unforeseen side effects, this caution must be balanced against the risks of continuing suboptimal care. Slow adoption can serve as a safety mechanism, but it does not prevent the occurrence of rare adverse events, such as aplastic anaemia. In the case of felbamate, during the honeymoon period of academia-industry relationships in the 1990s, it took less than 2 years to reach the critical safety milestone of 100 000 patient-years, compared to over 4 years for cenobamate.⁴Far more people will have died from sudden unexpected death in epilepsy (SUDEP) in these additional 2 years, as cenobamate has shown to be particularly effective in suppressing convulsions, the leading risk factor for SUDEP. Another instance is that it took 50 years to link phenobarbital to Dupuytren’s contractures, yet that hardly justified delaying its use for that long.

A recent Cochrane systematic review of cenobamate highlights this misguided ethical purity.⁷ Despite two large randomized controlled trials (RCTs) providing evidence of efficacy, the evidence grade was downgraded to ‘moderate’, solely because the drug manufacturer funded the studies. RCTs are a requirement for regulatory approval. The industry almost invariably sponsors such studies; expecting ‘unbiased’ sponsors is unrealistic. Reducing evidence levels solely based on commercial sponsorship is unscientific and potentially harmful, particularly given the significant influence that Cochrane reviews have on clinical practice, healthcare providers and reimbursement decisions.

Academia’s disengagement from pharmaceutical development and its negative perception of the industry are creating a concerning ripple effect: a decline in interest in clinical trials among the younger generation of medical professionals. Residents, fellows and junior faculty unexposed to clinical trials may have little interest in pursuing them. This trend further reduces academia's ability to contribute to the development of new treatments, negatively impacting the quality of clinical studies. Historically, industry has relied on the expertise of academic clinicians to refine trial designs and improve study quality. This crucial knowledge is now largely withheld due to academia’s reluctance to engage in collaboration. Unless academia and industry resume their partnership, this problem will only intensify as the older generation of academic clinical trialists retires without adequate replacement.

The ‘divorce’ between academia and industry has another serious consequence: a reduction in education about new treatments. Academics, often lacking experience with clinical trials of novel therapies, become hesitant to educate the broader medical community. For example, despite the efficacy of cenobamate and fenfluramine,^8,9 these drugs were conspicuously absent from all eight major symposia at the 2020 annual meeting of the American Epilepsy Society (AES)—a premier event whose programme is set by academic leadership. Even the meeting’s published summary made no mention of them,¹⁰ and coverage remained sparse through 2023. This is concerning, given that five new ASMs were approved between 2018 and 2023, yet the last non-commercial symposium on new epilepsy drug treatments at the AES meeting was in 2017. While industry-sponsored educational programmes featuring FDA-approved content have traditionally disseminated new drug knowledge, many academic centres now discourage faculty participation. This silences the academicians who were involved in the trials, preventing them from sharing vital information with peers. This effectively chokes the flow of expert knowledge to the medical community, a gap that hospital grand rounds have failed to fill.

Conflicts of interest exist, but a conflict of interest may be compatible with benefit to others. If a physician or an institution is paid for participating in a trial that leads to the development of a new treatment, that constitutes a potential conflict of interest. Yet the result may benefit people if the new treatment improves on existing treatments. Similarly, a potential conflict of interest arises when a company pays a healthcare provider to deliver a branded educational talk about a new treatment. This is now recognized in the publicly accessible Sunshine Act disclosures. Conflicts of interest are not unique to the pharmaceutical industry. Academics, for example, gain reputational benefits from presenting their research, which can influence their ability to secure future grants—an apparent conflict. Grant reviewers assessing applications within their research area also face conflicts of interest. Ultimately, potential conflicts of interest in healthcare providers’ engagement with the industry should be viewed in the same light as those in other areas of business. They should not serve as a blanket justification for banning ethical collaboration between academics and industry, nor for downgrading the levels of scientific evidence.

What, then, may be solutions? We could start by reviewing our assumptions: that one side—the industry—is bad, while academicians are blameless. We could then discuss what went wrong and how to rectify the mistakes. Collaboration between academia and industry would benefit everyone, particularly patients. The industry would benefit from academic clinicians’ re-engagement at every step of drug development:

• Treatment development and pipeline evaluation: The bi-annual Epilepsy Therapies and Diagnostics Development Symposium and the Eilat Conference on New ASMs are attended by companies with ASMs at various stages of development; however, few academic clinicians participate in these meetings.

• Trial designs and execution: The Epilepsy Study Consortium and the European Collaboration for Epilepsy Trials exemplify how experienced clinicians can advise the industry on trial design.

• Post-marketing surveillance: The group at University College London has a long tradition of auditing the retention of new ASMs, providing invaluable information without the restrictions of regulatory trials.

• Education of the medical community and the public: Academic institutions, speciality societies and other unbiased venues should increase education about new treatments through academic grand rounds, symposia, lectures, seminars and review articles. Information about new therapies may include more frequent updates from the AES and International League Against Epilepsy, as well as updates to clinical practice guidelines (last updated in 2018).

Divorces may be less messy if both parties are open to hearing each other. Surprisingly, the parties sometimes realize they have more in common than they thought. Perhaps that is the case with academia and the industry: we share a common interest in people suffering from diseases. For their sake, let us reflect.

Pavel Klein is a neurologist in private practice in the USA, Clinical Professor of Neurology at The George Washington University, previously Director of the Epilepsy Center at Georgetown University, engaged in patient care and clinical research focused on new treatments in epilepsy and epilepsy prevention involving both collaboration with the industry and US federal funding. Amanda Pong is a paediatric epileptologist with training in biostatistics and an interest in new therapies for drug-refractory epilepsy as seen in rare, genetic neurodevelopmental disorders. Matthias Koepp is Professor of Neurology at UCL and consultant neurologist at the National Hospital for Neurology and Neurosurgery, with extensive experience in epilepsy care, academic medicine, and clinical trials, providing him with a unique perspective on the interplay between research, industry, and the timely adoption of innovative treatments in clinical practice. Wolfgang Löscher is a Professor of Pharmacology and Toxicology with both academic and industry backgrounds and a particular interest in the development of new epilepsy therapies. Ley Sander is a Professor of Neurology and a consultant neurologist with extensive research experience in epilepsy, a strong track record in developing novel therapies, as evidenced by his many publications and significant contributions to the field. Edward Faught is a Professor of Neurology at Emory University, has been an investigator in 85 clinical trials funded by the National Institutes of Health, the US Department of Veterans Affairs, and industry, and served as Director of the Epilepsy Centers at Emory University and the University of Alabama at Birmingham.

Funding

No funding was received towards this work.

Competing interests

P.K. has served as a consultant, advisory board member or speaker (2020–2025) for Abbott, Angelini Pharma, Aquestive, Arvelle Therapeutics, Aucta Pharmaceuticals, Dr. Reddy's, Eisai, GRIN Therapeutics, Jazz Pharmaceuticals, Longboard Pharmaceuticals, Neurelis, Inc., Neurona Therapeutics, Paladin Pharma, SK Life Science, Sunovion, UCB Pharma, UNEEG, UniQure and Xenon Pharmaceuticals, is a member of the Medical Advisory Board of Stratus and of the Scientific Advisory Boards of OB Pharma and NEUmirna, is the CEO of PrevEp, Inc. and is member of the data and safety monitoring board for Neurona Therapeutics. A.P. has no conflict of interest. M.J.K. or his department have received grants from Angelini Pharma, Biohaven Therapeutics, UCB Pharma and Xenon Pharmaceuticals. Additionally, he has received consulting fees from Angelini Pharma, Biocodex, Eisai Pharmaceuticals, Jazz Pharmaceuticals, LivaNova, Sanofi and UCB Pharma. He is a co-founder of PrevEp, Inc. W.L. has received consulting fees from Addex Pharmaceuticals, Angelini Pharma, Lundbeck, Axonis Therapeutics, Clexio Biosciences and Selene Therapeutics, and is the CSO of PrevEp, Inc. J.W.S. or his department have received grants from Angelini Pharma and UCB Pharma. He has consulted for Angelini Pharma, SK Life Sciences and Jazz Pharma. E.F. has acted as a consultant to Biogen and LivaNova, served as a member of a Data Monitoring Board for SK Life Science and received Research Support from Cogenix, UCB Pharma and Xenon Pharmaceuticals.