Full video: https://youtu.be/pR6GoPogTwM?si=XP6COp3P3EXR4FcW

(almost verbatim)

Slide 1

Slide 1 Description: The title slide says "ethics in long covid research design" in blue and purple colored font. Underneath it says V. Copeland, Ph.D, MSW with input from Catherine Romatowski and individuals in the tired and wired and recover representative groups.

Audio transcription: Hello my name is Victoria and I wanted to thank the organizing team for inviting me to speak today. Im a policy researcher and social worker with a PhD and masters degree and I’m here today to share some points for reflection from myself and other people with severe manifestations of long COVID. Thank to Catherine and the other groups for feedback on this presentation.

Slide 2

Description: The title says Stats in purple font. On the side there are citations. The stats are as follows: 

• - One of most frequent symptoms after 6 months is post-exertional malaise (n=3762)
• - RECOVER Index PEM was prominent in all but one “subtypes” (n=13647)
• - Health outcomes study 36% of hospitalized patients reported PEM after 3 years 
• - In a RECOVER study (n=13224) people who had COVID-19 were ~ 5x more likely to meet diagnostic criteria for ME/CFS compared to those who did not.

Citations:

1. https://pubmed.ncbi.nlm.nih.gov/34308300/
2. https://jamanetwork.com/journals/jama/fullarticle/2828329
3. https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(25)00082-1/fulltext
4. https://link.springer.com/10.1007/s11606-024-09290-9

Audio transcription: Today I’m talking about clinical long COVID research and post exertional malaise. For those new to the term, pem is often defined as the prolonged worsening of symptoms following exertion whether that exertion is physical or cognitive. This is not just a form of exercise intolerance. It a serious adverse reaction to exertion and a serious condition. Pem can be temporary but it can also cause permanent worsening of one’s condition. Symptoms can include: syncope, seizures, severe. Neurological disturbances, excruciating pain and muscle weakness, nausea, and extreme sensory sensitivity. According to the research pem was found to be one of the most frequent symptoms following a COVID infection, with patients even reporting pem three years post acute infection. So Why is this important?

Slide 3

Description: title says Stats "Inclusion in Long covid trials" in blue and purple font. Under the title it says who are we missing? And why does it matter?  To the side is a rectangle with three parts. At the top of the rectangle is a green box that says no PEM, accessible. Beneath is a yellow box that says moderate PEM. Access considered. PEM inevitable byproduct. Beneath is a red box that says severe PEM. No access, non inclusion. On the side of the rectangle is text that's says this image os a hypothetical and not based on any research. The bottom of the slide is a citation box: https://www.mdpi.com/2075-4418/9/1/26.

Audio transcription: Well if we know that many people with long COVID also experience pem it’s very important that we take this into account when designing research.  this should not be just an afterthought for researchers but should be considered and planned for when designing trials from their conception.  one study shows that 67% of people with Myalgic Encephalomyelitis report crashes that never resolve. And this is vital information to know as we craft new clinical research. 

Here I’m highlighting that people with severe pem, meaning they rarely leave their homes or beds, are often fully excluded from trials. Further, upon hearing testimony from people who have pem but are not fully home or bedbound, they also have to expect pem as an inevitable byproduct of participating in a clinical trial. Although access may be briefly acknowledged by researchers, it is not baked into the research design and thus people with moderate pem risk permanently worsening just to participate in a trial and potentially be helped.

 If people with long COVID and severe PEM are largely stuck in their homes or beds and excluded from trials, is the long COVID research as it stands representative of the full population of people with long COVID? If not what and who are we missing? Further, is it ethical to knowingly conduct trials that may cause long term health consequences ? 

I pause here to acknowledge that Of course this is a difficult discussion to have. many patients fear speaking up for fear of losing the ability to participate in a trial and others fear that they cannot speak up about accessibility when there’s so much political pressure and controversy  around funding long COVID research in general. Patients with severe pem are stuck between a rock and a hard place. And I know some researchers are trying their best to navigate this contentious landscape.

Slide 4 and 5

Description: Just text below. Citation box to the side: 

https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html#xbenefit. 

Audio transcription: But this is still important for us to figure out. I wanted to take us back to the Belmont report. If you have a doctorate you have heard of this before but for those who may not know, in response to  the  violence of the Tuskegee experiments, the National Research Act of 1974 was passed and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was created. The Belmont report came from this commission in efforts to set guidelines for research involving human subjects.  

One of the three ethical principles in the report is beneficence. Under this principle it states that: 

"Persons are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being"

"…beneficence is understood in a stronger sense, as an obligation.”

(1) do not harm and (2) maximize possible benefits and minimize possible harms."

Additionally it states that:

“investigators . . .  are obliged to give forethought to . . . the reduction of risk that might occur from the research investigation”

“Risk can perhaps never be entirely eliminated, but it can often be reduced by careful attention to alternative procedures.”

I bring up this point to say that it is not just medical doctors who are responsible for upholding just and equitable care for their patients, but also researchers who are obligated to ethically navigate the risks and benefits of all research involving human participants.

This is not to say that trials should not be happening, but that we may need to become creative about the ways we engage in these trials, as we are dealing with a population of people who are incredibly ill and vulnerable to worsening without proper care.

Slide 6

Description: The title says prioritizing the individual. There's a picture in the center of an unbalanced scale with the left heavier than the right. To the left is text that's says: planning for confounding variables, internal and external validity, and finding constraints. To the right is text that says planning for: well being of trial participants, long term health impact.

Audio transcription: And yes of course this does not happen in a vacuum. It’s important for us to remember that researchers have to contend with planning for confounding variables, and the validity of findings. However we also have to weigh the well-being of patients which is what beneficence is pointing too. I have been on a call before where researchers were saying they cannot provide certain accessibility measures due to potentially muddying the data. However we also need to back these claims with science. 

To what extent will providing access impact the validity of the findings? Is that reduction in validity (either potential or proven) worth potentially disabling a participant by causing repeated or prolonged pem? These are the questions I am hoping researchers sit with.

Slide 7 & 8

Description: Just text as below. The title says beneficent action. 

Audio transcription: Here are some ways that patients have expressed we can reduce pem in trials. 

Reducing exertion: 
More capacious framework for time allotment, while acknowledging trial urgency. Here this is speaking to the need to understand that people with pem need more than one or two days for testing. Making patients choose between a 5-6 hour day of testing or two days of 3-4 hours of testing each may not actually be ethical when we are speaking of people with moderate or severe PEM. That is because even an hour of testing can cause a severe episode of pem. Several hours and back to back days both have ramifications on ones well-being that should be considered.

Use of mobile phlebotemy and at home tests and Requiring PPE at testing sites, and proper ventilation. I am shocked that it has to be stated so often but Infecting someone with COVID at a long COVID trial is just extremely offensive and violent and should not be happening. Providing lists of community resources upon visit. Multiple versions of consent, including plain language, written, and spoken prior to visit. Compensation for least exertional transport to site whether train, rideshare, gurney or wheelchair.

Slide 9

Description: Slide says thank you for watching and listening.

Audio transcription: I hope these questions and points raise some discussions about making more ethical trials and thank you for your time.