Society or population, social diversity. Flat cartoon vector illustration.

Unequal Representation: Race, Sex, and Trust in Medicine — COVID-19 and Beyond

By Allison M. Whelan*

The COVID-19 pandemic has given renewed importance and urgency to the need for racial and gender diversity in clinical trials.

The underrepresentation of women in clinical research throughout history is a well-recognized problem, particularly for pregnant women. This stems, in part, from paternalism, a lack of respect for women’s autonomy, and concerns about women’s “vulnerability.” It harms women’s health as well as their dignity.

Over the years, FDA rules and guidance have helped narrow these gaps, and recent data suggest that women’s enrollment in clinical trials that were used to support new drug approvals was equal to or greater than men’s enrollment. Nevertheless, there is still progress to be made, especially for pregnant women. In the context of COVID-19 research, one review of 371 interventional trials found that 75.8% of drug trials declared pregnancy as an exclusion criteria, a concerning statistic given that recent data suggest that contracting COVID-19 during pregnancy may increase the risk of preterm birth.

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Monthly Round-Up of What to Read on Pharma Law and Policy

By Ameet SarpatwariBeatrice Brown, Neeraj Patel, and Aaron S. Kesselheim

Each month, members of the Program On Regulation, Therapeutics, And Law (PORTAL) review the peer-reviewed medical literature to identify interesting empirical studies, policy analyses, and editorials on health law and policy issues.

Below are the citations for papers identified from the month of October. The selections feature topics ranging from a commentary calling for reconsideration of the FDA’s risk evaluation and mitigation strategy (REMS) program for mifepristone, to an analysis of clinical development times for biosimilars seeking FDA approval, to an editorial describing the challenges of using the Defense Production Act to address drug shortages. A full posting of abstracts/summaries of these articles may be found on our website.

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Young male doctor in telehealth concept

COVID-19’s Impact on Clinical Trials: Meeting Participants Where They Are

By Sarah V. Ferranti and Shine Chen Schattgen

“Decentralized” clinical trials (referred to as “DCTs”) are not novel, but nevertheless failed to gain real momentum given the regulatory and operational complexities involved. In light of COVID-19, however, it seems almost certain that the remote and virtual study activities that characterize DCTs, and a site and sponsor’s ability to flex to “meet the participant where they are” will be critical to the conduct of clinical trials going forward.

In the first half of 2020, as health care facilities prepared for capacity-exceeding patient volumes and equipment shortages, non-essential clinical care and non-COVID-related clinical trials came to a screeching halt. According to ClinicalTrials.gov, 1473 clinical trials were suspended, terminated, or withdrawn between December 1, 2019 and July 1, 2020, with a reported reason that explicitly mentioned COVID-19.

At the same time, initiation of clinical trials for COVID-19 vaccines and treatments exploded at speeds previously considered unachievable within the clinical trial industry. As of October 13, 2020, 811 COVID-19-related clinical trials had been initiated in the United States. To enable COVID-19 trials and, more recently, to restart previously paused non-COVID trials, clinical trial sponsors and sites have been forced to quickly adapt to protect participants and preserve the integrity of clinical trial data and results.

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a pill in place of a model globe

Monthly Round-Up of What to Read on Pharma Law and Policy

By Ameet SarpatwariBeatrice Brown, Neeraj Patel, and Aaron S. Kesselheim

Each month, members of the Program On Regulation, Therapeutics, And Law (PORTAL) review the peer-reviewed medical literature to identify interesting empirical studies, policy analyses, and editorials on health law and policy issues.

Below are the citations for papers identified from the month of August. The selections feature topics ranging from a commentary on the need for rigorous scientific evaluation of COVID-19 vaccine candidates in the face of political and economic pressures, to an evaluation of patients’ and pharmacists’ experiences with pill appearance changes, to an examination of the extent and cost of potentially inappropriate prescription drug prescriptions for older adults. A full posting of abstracts/summaries of these articles may be found on our website.

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Minneapolis, MN / USA - May 26 2020: Black Lives Matter, "I Can't Breathe" Protest for George Floyd.

Expendable Lives and COVID-19

By Matiangai Sirleaf

Two French doctors recently appeared on television and discussed using African subjects in experimental trials for an antidote to the novel coronavirus (COVID-19).

“Shouldn’t we do this study in Africa, where there are no masks, no treatment, no resuscitation, a bit like some studies on AIDS, where among prostitutes, we try things, because they are exposed, and they don’t protect themselves. What do you think?” asked Jean-Paul Mira, head of the intensive care unit at the Cochin Hospital in Paris on April 1, 2020.

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an ambulance parked at the entrance of an emergency department

Racial Disparities Persist in Human Subjects Research

By Beatrice Brown

Human subjects research has long been plagued by racial inequality. While flagrant abuses have been curtailed, disparities have, unfortunately, persisted.

One area ripe for scrutiny is clinical trial enrollment. A 2018 study by William Feldman, Spencer Hey, and Aaron Kesselheim in Health Affairs documents racial disparities in trials that are exempt from typical requirements for informed consent from study participants.

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Pills spilling out of a few bills rolled in a cylinder

The Funding Effect: How Drug Manufacturers Design Clinical Trials to Produce Favorable Results

By Ryan J. Duplechin

Many consumers are unaware that the U.S. Food and Drug Administration (“FDA”) does not test drugs in the approval process. Instead, drug manufacturers test their drugs and submit their own results to the FDA for review. Hoping to convince the FDA and investors of the safety and effectiveness of their new drug, manufacturers go to great lengths to report positive results in clinical trials. Read More

Kidneys and Livers, Made to Order?

By Seán Finan

Last week, Organovo might just have revolutionised the pharmaceutical industry. The San Diego-based company specialises in producing structures that mimic the behaviours and functions of human tissue, using 3D bioprinting. They announced last week that they were beginning the commercial manufacture and sale of their ExVive Kidney. The product models the proximal tubule of the human kidney and holds significant promise for clinical trials of new drugs. The commercialization of the ExVive Kidney follows the release of ExVive Human Liver Tissue in 2014.

In essence, Organovo is using 3D printing technology to produce samples of “human” tissue that can be used to test the toxicity of new drugs. The printing process, known as 3D bioprinting, involves extracting human cells, culturing them and suspending them in a solution. The resulting “bioink” is fed through a modified 3D printer. Layer by layer, the printer deposits cells, producing a mass with a similar structure and density to a sample of, for example, human liver. Just like “organ on a chip” technology, these synthetic liver and kidney samples present significant advantages over traditional clinical testing.

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European Responses to the Ebola Crisis: Initiatives at the European Medicines Agency (EMA)

By Timo Minssen

The current Ebola outbreak already attracted much attention on “Bill of Health” resulting in some excellent blogs on a horrible topic.

While it is evident that the current health crisis requires both immediate responses and more sustainable changes in health care policy, research and regulation, medicines regulators are collaborating internationally to find innovative solutions enhancing evaluation of and access to potential new medicines to fight Ebola outbreaks. In a statement announced by the International Coalition of Medicines Regulatory Authorities (ICMRA) in September 2014, regulators around the world led by the FDA and the EMA have vowed to collaborate in supporting accelerated evaluation of experimental new drugs to treat Ebola virus infections and say they will encourage submission of regulatory dossiers. This clearly backs up the World Health Organization’s (WHO) decision to test experimental Ebola treatments in infected patients in the current outbreak region in West Africa and to speed up the development of vaccines.

In the following I would like to summarize and discuss some of the recent European responses to the current crisis starting with an overview on recent initiatives at the EMA.

Like its US counterpart, the EMA leads a close and consistent dialogue with public and private developers of Ebola products and spends much effort in reviewing available information on the various experimental Ebola treatments currently under development. These experimental drugs range from experimental antivirals or vaccines based on the adenovirus or stomatitis vaccine to experimental therapies based on mono- and polyclonal antibody technologies. One of these unapproved antibody combination drugs – MAPP Biologicals’  ZMapp – has already been used in some care workers affected by Ebola. Other experimental drugs that are currently reviewed by the EMA include Biocryst’s BCX 4430, Fab’entech’s Hyperimmune horse sera, Sarepta’s AVI-7537, Toyama Chemicals and MediVector’s Favipiravir and Tekmira’s TKM-Ebola.

Other companies such as Bavarian Nordic  and the Russian Mikrogen are close to follow.

In addition to monitoring experimental drugs and enhancing global collaboration, the European Medicines Agency has like the FDA initiated several activities in order to support and speed up the development of these drugs towards market approval.  Read More

Bumps on the Road Towards Clinical Trials Data Transparency- A recent U-Turn by the EMA?

By Timo Minssen

In a recent blog I discussed the benefits and potential draw-backs of a new “EU Regulation on clinical trials on medicinal products for human use,” which had been adopted by the European Parliament and Council in April 2014. Parallel to these legislative developments, the drug industry has responded with its own initiatives providing for varying degrees of transparency. But also medical authorities have been very active in developing their transparency policies.

In the US, the FDA proposed new rules which would require disclosure of masked and de-identified patient-level data. In the EU, the EMA organized during 2013 a series of meetings with its five advisory committees to devise a draft policy for proactive publication of and access to clinical-trial data. In June 2013 this process resulted in the publication, of a draft policy document titled “Publication and access to clinical-trial data” (EMA/240810/2013).

Following an invitation for public comments on this document, the EMA received more than 1,000 submissions from stakeholders. Based on these comments the EMA recently proposed “Terms of Use” (TOU) and “Redaction Principles” for clinical trial data disclosure.

In a letter to the EMA’s executive director Dr. Guido Rasi, dated 13 May 2014, the European Ombudsman, Emily O’Reilly, has now expressed concern about what seems to be a substantial shift of policy regarding clinical trial data transparency. Read More