Federal funding of research has decreased over the past decade.1 At the same time, NIH has called for more collaboration between industry and academic investigators. For example, NIH’s Discovering New Therapeutic Uses for Existing Molecules initiative will test more than 20 compounds from industry partners for their effectiveness against a variety of diseases and conditions.2 Accelerating Medicine Partnerships is a collaboration among NIH, ten pharmaceutical companies, and non-profit patient advocacy organizations to identify and validate the most promising biological targets of disease for new diagnostic and drug development.3 “Clearly, we need to speed the pace at which we are turning discoveries into better health outcomes,” said NIH Director Collins. “NIH looks forward to working with our partners in industry and academia to tackle an urgent need that is beyond the scope of any one organization or sector”.4 Additionally, since passage of the Patent and Trademark Law Amendments (“Bayh–Dole”) Act of 1980,5 many academic institutions encourage faculty to patent and commercialize their discoveries, leading to mutually—scientifically and financially—beneficial partnerships between universities, their individual scientists, and private sector companies. In the wake of this engagement between academia and industry, and the enhanced scrutiny of industry payments to physicians prompted by passage of the Physician Payment Sunshine Act,6 universities nationwide are revising their guidelines for conducting research and managing conflicts of interest.

Industry and government together have consistently funded most medical research in the U.S. (Fig. 1). Notably, industry dominates: research funding by industry in 2012 was $68 billion compared to $38 billion from federal agencies. Moreover, between 1994 and 2012, industry funding of medical research grew by 147 %, compared with 48 % for federal agencies, which was less than the 57 % inflation during those years.7 The goal of federal research funding is to generate new knowledge that will enhance health and health care. The goal of research funding by for-profit companies is maximizing income to their shareholders. Increased knowledge and enhanced care, if they happen at all, are byproducts of the profit motive.

Fig. 1
figure 1

Growth in medical research funding by source from 1994 to 2012 ($, in billions)1

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Can academicians’ interest and industry’s needs be aligned? For example, a company developing a new drug that may have fewer side effects might be interested in funding research into the incidence of adverse effects from currently marketed drugs. An academic researcher might have a strong interest in elucidating the adverse effect profile of that class of drugs when used in everyday settings among patients who are usually, if not always, excluded from pre-marketing studies.8 Studies of how drugs and devices are used in everyday practice and the outcomes of treatment should be of mutual interest and benefit to both academic researchers and industry. For example, Bristol-Myers Squibb was about to launch a new antipsychotic drug and contracted with one of us (WMT) to conduct a study of the incidence of weight gain and diabetes among patients taking any of the currently available antipsychotics; the results were published in JGIM. 9

Both academia and industry have interests in post-marketing drug surveillance.10 The FDA requires companies to conduct post-marketing surveillance (phase IV studies) of new drugs and certain devices. Whereas academic investigators are interested in true estimates of benefits and risks of new treatments, for-profit drug and device companies would want to report great benefits and low risks. We believe that academic researchers are more likely to perform unbiased post-marketing studies than either researchers employed by the company marketing the drug in question or for-profit research companies whose livelihood depends on satisfying their customers.

Academic researchers and industry scientists can also share interests in generating knowledge relevant to patient care. For example, clinicians hope and expect patients to take the medications they prescribe, and pharmaceutical companies benefit when patients take them. Thus both clinician-investigators and pharmaceutical companies have obvious interests in drug adherence and in developing and validating methods for assessing and improving adherence. Industry and academic investigators can also have mutual interests in improving our ability to identify, assess, and manage important patient outcomes. For example, the Regenstrief Institute has a five-year contract with Merck Sharp & Dohme to develop and conduct mutually interesting and beneficial research projects.11 Researchers from the Regenstrief Institute and Indiana University and scientists from Merck propose collaborative one-year projects. A review committee comprising three senior investigators from both IU/Regenstrief and Merck reviews the proposals, eliminates some, and ranks the rest. Merck decides on its allocation to the collaboration each year, and then the review committee begins at the top of the rank list and funds projects until all allocated funds are expended. Publication of study results in peer-reviewed journals is a required deliverable of each project. Table 1 shows projects funded in the first four years of this collaboration. Importantly, like federally funded projects, the grants reimburse the salaries of IU/Regenstrief investigators and professional staff. No bonuses or extra payments are made.

Table 1 Funding of Projects in the First Four Years of the Regenstrief-Merck Collaboration
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Industry-funded research has a risk of bias and misconduct that can mislead readers,12–14 consequently causing pain, suffering, and sometimes death.15 Neither academia nor the private sector is immune from ethical scrutiny or responsibility, though public perception rarely gives high marks to the pharmaceutical industry’s ethical behavior.16 The key is minimizing bias through rigorous studies devised, conducted, and reported by academic investigators whose income is not tied to the drug being evaluated. Each of these—research methods, how they are applied, and how results are reported—is a source of bias, regardless of funding source, that rigor and vigilance can minimize in order to generate new knowledge and patient benefit.

For example, Kroenke and his colleagues received funding from Pfizer to develop screening instruments for depression (the PHQ-9) and anxiety (the GAD-7).17 Both have become standard screening tools. The JGIM original article validating the PHQ-918 has been cited more than 3500 times, according to Web of Science19; it is JGIM’s most highly cited article ever. Whereas both the PHQ-9 and GAD-7 are open-source and free to use, some survey instruments developed with federal funding require license fees,20 an unfortunate trend where patient-reported measures are frequently proprietary rather than in the public domain.21

Certainly there are well-documented cases where industry-funded research has been biased. For example, two systematic reviews found that studies sponsored by industry reported significantly greater benefits and less harm than studies with other sources of funding.22,23 Similarly, there are well-known examples where industry has squelched (or attempted to squelch) study results that were unfavorable to their products.24,25 Pharmaceutical companies have also paid ghostwriters to draft reviews of drug treatment favorable to their products, and then sought academicians to “author” the articles, with the goal of biasing the medical literature.26 But does such obviously unethical behavior by some investigators and companies mean that industry-funded research can never be conducted by academic scientists without the results being questioned? We argue that academic–industry relationships can be “ethically credible,” meaning that specific ethical principles are followed that minimize the risk that industry funding will bias the planning, conduct, or reporting of studies. Indeed, academic–industry relationships are not only possible, they are desirable as a means to maximize discoveries and patient benefits as federal research dollars are dwindling.

An example of an ethically credible partnership was the ARTIST study that was funded by Eli Lilly to assess the effects of different selective serotonin reuptake inhibitors (SSRIs) on depression and other outcomes in primary care.27 The sponsor had postulated that its SSRI (fluoxetine) would be more effective than two competing SSRIs (sertraline and paroxetine). However, the study found no differences among the three SSRIs as reported in a high-impact journal (JAMA), despite not favoring the sponsor’s drug. Indeed, the evidence supporting “funding bias” has recently been questioned by social scientists as well as the Cochrane collaboration.28,29

To counter potential bias due to industry funding of research, the Regenstrief Institute commissioned one of us (EMM) and his colleagues at the Indiana University Center for Bioethics (IUCB) to review Regenstrief’s collaboration with Merck.11 Reviews of this kind are rare, but have been reported elsewhere.30 During the second year of the five-year collaboration, IUCB faculty and staff reviewed the contract between Regenstrief and Merck, assessed the bioethics literature concerning industry-funded research, surveyed Indiana University/Regenstrief investigators and staff engaged in one or more Merck-funded activities, and developed a set of principles and benchmarks for ethically credible academic–industry partnerships (Table 2). IUCB reviewers found the Regenstrief-Merck collaboration to be ethically conducted overall, but that it could be improved, especially in communicating the collaboration’s policies and operating principles to all faculty and staff participants.31 The policies and procedures governing the Regenstrief-Merck collaboration were deemed to address the key ethical issues. Several benchmarks were not fully met, and the report made specific recommendations that the collaboration’s leaders followed. In subsequent years, the collaboration has met all benchmarks. Specific recommendations followed were to 1) increase transparency and enhance trust by more fully educating all investigators and staff on the collaboration’s policies and procedures; 2) broadcast the processes for ranking projects and selecting those to be funded; 3) include a wider range of Institute and university investigators in the invitation to propose studies; 4) publicize the collaboration’s distinctive conflict of interest policies; and 5) proactively assess investigators’ concerns about the collaboration and provide investigators with more opportunities to learn about the collaboration and provide input.

Table 2 Principles and Benchmarks for Ethically Credible Academic–Industry Partnerships
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As a result of the IUBC evaluation and the more than two decades of research collaboration with industry, the Regenstrief Institute has launched an Industry Research Office (IndRO) that facilitates conversations with prospective industry funders, identifies Regenstrief and other university principle investigators and co-investigators, helps design protocols and write proposals, manages communication and contracts, and follows the principles and benchmarks for a wider range of investigators, funders, and studies. The overriding goal of the IndRO is to provide academic researchers with alternative sources of funding their research as federal sources become increasingly constrained. In addition to faculty and staff salaries for performing research, funds from industry-sponsored studies support IndRO’s management infrastructure, local clinical data repositories, and other research resources. To maintain the studies’ intellectual independence and scholarly focus, all industry contracts contain a clause giving the investigators the right to publish any and all study results, and an article submitted to a peer-reviewed journal is the final required deliverable of all contracts.

The moral outrage engendered by past misbehavior on the part of the drug and device industry and academic researchers can affect all financial relationships between medical schools and industry.32,33 If stringent ethical guidelines are followed, private sector companies can be an important source of funding for ethical, high-quality, important academic research. Universities must develop and implement policies and procedures to maximize the effectiveness and ethical conduct of all research, regardless of funding source. We are confident that this is possible and that industry, academic medical scientists, and the patients and communities they serve can all benefit.