The FDA’s approval of blurring the treatment and research divide: an opportunity to reconcile enhanced knowledge with patient rights?

By Marielle Coutrix*

On December 13, 2016 President Obama signed into law the 21st Century Act with broad bipartisan support.[i]The Act provides multi-year funding to the National Institutes of Health for a number of crucial biomedical initiatives including brain cancer and stem cell research.[ii]The Act also, and more controversially, called for an overhaul of the U.S. “cycle of discovery, development and delivery of innovative medical products,” authorizing the Food and Drug Administration (FDA) to consider real world evidence (RWE) when approving new drugs[iii].

RWE is a silent revolution in health research. The use of real-world evidence is a significant departure from the FDA’s previous reliance on experimental trials to gauge the risks and benefits of certain drugs before making them available (or not) for public use[iv]. Reliance on RWE brings medical testing outside of the laboratory, enabling pharmaceutical companies to use patients’ electronic health records, disease registries and billing records to evaluate the effectiveness of their drugs and vouch for post-marketing approval.[v]There is strong pushback, however, against RWE animated by the fear that this regulatory scheme lowers the evidence standards for product promotion.[vi]As the FDA moves to refine its RWE framework, debate lingers overwhat standards of evidence are practical, possible and ethically-sound to implement.

For one, RWEs offer an opportunity to bypass the shortcomings of the conventional drug approval process.[vii]Traditionally, this process is grounded in evaluating data from randomized control trials (RCTs). As the gold-standard in research, RCTs are useful at evaluating the efficacy of drugs under experimental conditions.[viii]They say less, however, about the effectiveness of treatments in real settings.[ix]By requiring random allocation of individuals in treatment and placebo control groups, RCTs are also notorious for being time-consuming and expensive to conduct.[x]With ever increasing clinical trial costs and compensatory drug price hikes, both innovation and patient access to treatment come under threat.[xi]RWEs can be used to circumvent these costsand increase access to affordable medicine.

Nonetheless, the use of RWEs has given rise to a whole new set of practical challenges, many of which will continue to emerge under the FDA’s full-blown implementation of the new real world approach. Emerging concerns also center on data reliability[xii]. Research training and data-sharing systems are not yet in place to optimize the use of raw data available from health care treatments.[xiii]This lack of standardized data collection and dissemination lowers the generalizability and accuracy of real world data, reducing the quality of evidence and making it difficult to draw comparisons among different products[xiv]. These shortcomings call for more investments in transforming our health care system into a learning health system that can take full advantage of what real world evidence has to offer.[xv]

The use of real world evidence for post-marketing approval also implicates deep ethical concerns. Because there are few incentives for pharmaceutical companies to evaluate the effectiveness of drugs that are already making a profit, critics fear that RWE is opening our health system to health care fraud and abuse. [xvi]Real world evidence also blurs the linesbetween experimentation and treatment[xvii], shaking the very foundation of bioethics[xviii]. Medical research is governed by a strict ethical code that requires informed consent for human participation in research and establishes confidentiality and privacy safeguards.[xix]Some critics argue that these lines are not blurring fast enough precisely because ethical codes are preventing the extrapolation of data from treatment and thus stripping post-marketing approval of the real-world evidence it needs to function.[xx]

Given RWE’s benefits for the advancement of medical knowledge, this ethical quagmire is worth solving, quickly. Some experts in the field have suggested that an atomistic conception of autonomy is ill-suited to address the dilemma[xxi], advocating instead for a reconceptualization of patients’ role in the healthcare system. They argue that patients have a right to health care but have a civic duty to generate new learning and thus participate in research.[xxii]In their ideal, if a patient seeks treatment, it should be assumed that the patient has consented to offering their health data to research.

An alternative is to use real world evidence and post-marketing approval as an opportunity to reconcile the advancement of medical knowledge with patient rights. Since real world evidence blurs the research-treatment divide and breaks with the assurances we once had of drug effectiveness, it may be worth institutionalizing informed consent in health care treatment. Consent for research could then be grafted onto the consent process in health care. For each treatment offered, patients would be informed about the drugs they have been prescribed and relevant approvals, and then asked to consent to care and research. The strength of this consent-heavy approach is that real world evidence would be the impetus for an institutionalized dialogue between patients and doctors about drug quality, research and health. Patients would be more informed about and conscious of the choices they make with respect to their own health and data, and the health of their community. A patient would have the duty to be better informed, and to take full responsibility for a decision to participate, or not, in research every time they receive treatment.

Underlying FDA’s modernization was the desire to “keep America at the forefront of medical innovation,” by getting “new treatments to patients and providers faster”.[xxiii]Underneath this important and timely objective lie deep ethical and logistical considerations. As the FDA refines its real-world evidence framework, we are left to wonder what role our own health will play. The use of real word evidence is an opportunity for patient approval to be a cornerstone of the new drug approval process.

*Marielle Coutrix is a Junior Editor on MJEAL. She can be reached at

The views and opinions expressed in this blog are those of the authors only and do not reflect the official policy or position of the Michigan Journal of Environmental and Administrative Law or the University of Michigan.

[i]Juliet Eilperin & Carolyn Y. Johnson. Obama, paying tribute to Biden and bipartisanship, signs 21st Century Cures Act Tuesday. The Washington Post, Dec. 13 2016,

[ii]J. Manag. The Potential Effect of the 21st Century Cures Act on Drug Development Care, Journal of Managed Care & Specialty Pharmacy 24, no. 7 (2018).

[iii]U.S. House of Representatives Committee on Energy and Commerce. Implementing the 21st Century Cures Act: An Update from FDA and NIH. Nov. 28, 2017,

[iv]W. Nicholson Price. Drug Approval in a Learning Health System, Minn. L. Rev. 102 (2018).

[v]Joan H. Krause & Richard S. Saver.Real-World Evidence in the Real World: Beyond the FDA, American Journal of Law & Medicine44, no. 2–3 (2018).



[viii]J. Manag. The Potential Effect of the 21st Century Cures Act on Drug Development Care, Journal of Managed Care & Specialty Pharmacy 24, no. 7 (2018).

[ix]Zuidgeest, Mira G.P. et al. Series: Pragmatic trials and real-world evidence: Paper 1. Introduction, Journal of Clinical Epidemiology 88, no. 7 (2017).

[x]Roger Collier. Rapidly rising clinical trial costs worry researchers, CMAJ 180, no. 3 (2009).


[xii]Krause & Saver supranote 5.

[xiii]Price, supranote 4.

[xiv]Krause & Saver supranote 5.

[xv]Price, supranote 4.

[xvi]Krause & Saver supranote 5.

[xvii]Price, supranote 4.

[xviii]National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research(1978) (three core principles are respect for persons, beneficence, and justice).

[xix]World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects, JAMA 10, no. 20 (2013).

[xx]Price, supranote 4.

[xxi]Barbara J. Evans. Power to the People: Data Citizens in the Age of Precision Medicine, Vanderbilt Journal of Entertainment & Technology Law. (2017); Barbara J. Evans. The Ethics of Postmarketing Observational Studies of Drug Safety Under 505(o)(3) of the Food, Drug, and Cosmetic Act, American Journal of Law & Medicine 38 (2012).

[xxii]Ruth R. Faden et al. An Ethics Framework for a Learning Health Care System: A Departure from Traditional Research Ethics and Clinical Ethics, Hastings Cent Report, no. S16-27 (2013).

[xxiii]U.S. House of Representatives Committee on Energy and Commerce. Implementing the 21st Century Cures Act: An Update from FDA and NIH. Nov. 28, 2017,

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