Thousands of Vaccine Volunteers Got a Dummy Shot. Should They Get the Real Deal Now?
If a treatment or prevention is known to work, it is considered unethical to withhold it from volunteers in order to prolong a research trial, experts say.
The highly anticipated rollout of a COVID-19 vaccine poses ethical considerations: When will trial volunteers who got a placebo be vaccinated? And how will this affect the data in those trials?
It's an issue that vaccine manufacturers and study investigators are wrestling with as the Food and Drug Administration is expected to grant emergency use authorization this weekend to a vaccine developed by Pfizer and the German company BioNTech. Another vaccine, produced by Moderna, is nearing approval in the United States.
The most vulnerable—health care workers and nursing home residents—are deemed eligible to receive the initial limited supply in accordance with priority recommendations from the Centers for Disease Control and Prevention (CDC).
With health care workers constituting an estimated 20 percent of trial participants, this question also comes to the fore: "Is it now ethically imperative that we offer them the vaccine, those who have had placebo?" says William Schaffner, an infectious diseases physician at Vanderbilt University and an adviser to the CDC's immunization practices committee.
When a "gold-standard" measure becomes available, participants in the placebo group "would ordinarily be notified" of the strong public health recommendation to opt for immunization, says Johan Bester, interim assistant dean for biomedical science education and director of bioethics at the University of Nevada, Las Vegas School of Medicine.
"If a treatment or prevention exists that we know works, it is unethical to withhold it from people who would benefit from it just to answer a research question." This moral principle poses a quandary for ethicists and physicians alike, as they ponder possible paths to proceed with vaccination amid ongoing trials. Rigorous trials are double-blinded—neither the participants nor the investigators know who received the actual vaccine and who got a dummy injection.
"The intent of these trials is to follow these folks for up to two years," says Marci Drees, infection prevention officer and hospital epidemiologist for ChristianaCare in Wilmington, Delaware. At a minimum, she adds, researchers would prefer to monitor participants for six months.
"You can still follow safety over a long-term period of time without actually continuing to have a placebo group for comparison."
But in the midst of a pandemic, that may not be feasible. Prolonged exposure to the highly contagious and lethal virus could have dire consequences.
To avoid compromising the integrity of the blinded data, "there are some potentially creative solutions," Drees says. For instance, trial participants could receive the opposite of what they initially got, whether it was the vaccine or the placebo.
One factor in this decision-making process depends on when a particular trial is slated to conclude. If that time is approaching, the risk of waiting would be lower than if the trial is only halfway in progress, says Eric Lofgren, an epidemiologist at Washington State University who has studied the impact of COVID-19 in jails and at in-person sporting events.
Sometimes a study concludes earlier than the projected completion date. "All clinical trials have a data and safety monitoring board that reviews the interim results," Lofgren says. The board may halt a trial after finding evidence of harm, or when a treatment or vaccine has proven to be "sufficiently good," rendering it unethical to deprive the placebo group of its benefits.
The initial months of a trial are most crucial for assessing a vaccine's safety. Differences between the trial groups would be illuminating if fewer individuals who got the active vaccine contracted the virus and developed symptoms when compared to the placebo recipients. After that point, in vaccine-administered participants, "you can still follow safety over a long-term period of time without actually continuing to have a placebo group for comparison," says Dial Hewlett Jr., medical director for disease control at the Westchester County Department of Health in New York.
Even outside of a trial, safety is paramount and any severe side effects that occur will be closely monitored and investigated through national reporting networks. For example, regulators in the U.K. are investigating several rare but serious allergic reactions to the Pfizer vaccine given on Tuesday. The FDA has asked Pfizer to track allergic reactions in its safety monitoring plan, and some experts are proposing that Pfizer conduct a separate study of the vaccine on people with a history of severe allergies.
As the FDA eventually grants authorization to multiple vaccines, more participants are likely to leave trials and opt to be vaccinated. It is important that enough participants choose to stay in ongoing trials, says Nicole Hassoun, professor of philosophy at the State University of New York at Binghamton, where she directs the Global Health Impact program to extend medical access to the poor.
She's hopeful that younger participants and individuals without underlying medical conditions will make that determination. But the departure of too many participants at high risk for the virus would make it more difficult to evaluate the vaccine's safety and efficacy in those populations, Hassoun says, while acknowledging, "We can't have the best of both worlds."
Once a safe and effective vaccine is approved in the United States, "it would not be ethically appropriate to do placebo trials to test new vaccines."
One solution would entail allowing health care workers to exit a trial after a vaccine is approved, even though this would result in "a conundrum when the next group of people are brought forward to get the vaccine—whether they're people age 65 and older or they're essential workers, or whoever they are," says Vanderbilt physician Schaffner, who is a former board member of the Infectious Diseases Society of America. "All of a sudden, you'll have an erosion of the volunteers who are in the trial."
For now, one way or another, experts agree that current and subsequent trials should proceed. There is a compelling reason to identify additional vaccines with potentially greater effectiveness but with fewer side effects or less complex delivery methods that don't require storage at extremely low temperatures.
"Continuing with existing vaccine trials and starting others remains important," says Nir Eyal, professor and director of Rutgers University's Center for Population-Level Bioethics in New Brunswick, New Jersey. "We still need to tell how much proven vaccines block infections and how long their duration lasts. And populations around the world need vaccines that are easier to store and deliver, or simply cheaper."
But once a safe and effective vaccine is approved in the United States, "it would not be ethically appropriate to do placebo trials to test new vaccines," says bioethicist Bester at the University of Nevada, Las Vegas School of Medicine. "One possibility if a new vaccine emerges, is to test it against existing vaccines."
In a letter sent to trial volunteers in November, Pfizer and BioNTech committed to establishing "a process that would allow interested participants in the placebo group who meet the eligibility criteria for early access in their country to 'cross-over' to the vaccine group." The trial plans to continue monitoring all subjects regardless of whether people in the placebo group cross over, Pfizer said in a presentation to the FDA today. After Pfizer has collected six months of safety data, in April 2021, it plans to ask the FDA for full approval of the vaccine.
In the meantime, the company pledged to update volunteers as they obtain more input from regulatory authorities. "Thank you again for making a difference by being a part of this study," they wrote. "It is only through the efforts of volunteers like you that reaching this important milestone and developing a potential vaccine against COVID-19 is possible."
CORRECTION: An earlier version of this article mistakenly stated that the FDA would be granting emergency "approval" to the Pfizer/BioNTech vaccine, rather than "emergency use authorization." We regret the error.
The Friday Five: Artificial DNA Could Give Cancer the Hook
In this week's Friday Five, artificial DNA could give cancer the hook. Plus, research suggests that this daily practice can improve relationships, social media could be good for finding factual information, injecting a gel may speed up recovery from injuries, and a blood pressure medicine is promising for a long healthy life.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- Artificial DNA gives cancer the hook
- This daily practice could improve relationships
- Can social media handle the truth?
- Injecting a gel could speed up recovery
- A blood pressure medicine for a long healthy life
9 Tips for Online Mental Health Therapy
Research shows that, for most patients, online therapy offers the same benefits as in-person therapy, yet many people still resist it. A behavioral scientist explains how you can use it to improve mental health.
Telehealth offers a vast improvement in access and convenience to all sorts of medical services, and online therapy for mental health is one of the most promising case studies for telehealth. With many online therapy options available, you can choose whatever works best for you. Yet many people are hesitant about using online therapy. Even if they do give it a try, they often don’t know how to make the most effective use of this treatment modality.
Why do so many feel uncertain about online therapy? A major reason stems from its novelty. Humans are creatures of habit, prone to falling for what behavioral scientists like myself call the status quo bias, a predisposition to stick to traditional practices and behaviors. Many people reject innovative solutions even when they would be helpful. Thus, while teletherapy was available long before the pandemic, and might have fit the needs of many potential clients, relatively few took advantage of this option.
Even when we do try new methodologies, we often don’t do so effectively, because we cling to the same approaches that worked in previous situations. Scientists call this behavior functional fixedness. It’s kind of like the saying about the hammer-nail syndrome: “when you have a hammer, everything looks like a nail.”
These two mental blindspots, the status quo bias and functional fixedness, impact decision making in many areas of life. Fortunately, recent research has shown effective and pragmatic strategies to defeat these dangerous errors in judgment. The nine tips below will help you make the best decisions to get effective online therapy, based on the latest research.
Trust the science of online therapy
Extensive research shows that, for most patients, online therapy offers the same benefits as in-person therapy.
For instance, a 2014 study in the Journal of Affective Disorders reported that online treatment proved just as effective as face-to-face treatment for depression. A 2018 study, published in Journal of Psychological Disorders, found that online cognitive behavioral therapy, or CBT, was just as effective as face-to-face treatment for major depression, panic disorder, social anxiety disorder, and generalized anxiety disorder. And a 2014 study in Behaviour Research and Therapy discovered that online CBT proved effective in treating anxiety disorders, and helped lower costs of treatment.
During the forced teletherapy of COVID, therapists worried that those with serious mental health conditions would be less likely to convert to teletherapy. Yet research published in Counselling Psychology Quarterly has helped to alleviate that concern. It found that those with schizophrenia, bipolar disorder, severe depression, PTSD, and even suicidality converted to teletherapy at about the same rate as those with less severe mental health challenges.
Yet teletherapy may not be for everyone. For example, adolescents had the most varied response to teletherapy, according to a 2020 study in Family Process. Some adapted quickly and easily, while others found it awkward and anxiety-inducing. On the whole, children with trauma respond worse to online therapy, per a 2020 study in Child Abuse & Neglect. The treatment of mental health issues can sometimes require in-person interactions, such as the use of eye movement desensitization and reprocessing to treat post-traumatic stress disorder. And according to a 2020 study from the Journal of Humanistic Psychology, online therapy may not be as effective for those suffering from loneliness.
Leverage the strengths of online therapy
Online therapy is much more accessible than in-person therapy for those with a decent internet connection, webcam, mic, and digital skills. You don’t have to commute to your therapist’s office, wasting money and time. You can take much less medical leave from work, saving you money and hassle with your boss. If you live in a sparsely populated area, online therapy could allow you to access many specialized kinds of therapy that isn’t accessible locally.
Online options are much quicker compared to the long waiting lines for in-person therapy. You also have much more convenient scheduling options. And you won’t have to worry about running into someone you know in the waiting room. Online therapy is easier to conceal from others and reduces stigma. Many patients may feel more comfortable and open to sharing in the privacy and comfort of their own home.
You can use a variety of communication tools suited to your needs at any given time. Video can be used to start a relationship with a therapist and have more intense and nuanced discussions, but can be draining, especially for those with social anxiety. Voice-only may work well for less intense discussions. Email offers a useful option for long-form, well-thought-out messages. Texting is useful for quick, real-time questions, answers, and reinforcement.
Plus, online therapy is often cheaper than in-person therapy. In the midst of COVID, many insurance providers have decided to cover online therapy.
Address the weaknesses
One weakness is the requirement for appropriate technology and skills to engage in online therapy. Another is the difficulty of forming a close therapeutic relationship with your therapist. You won’t be able to communicate non-verbals as fully and the therapist will not be able to read you as well, requiring you to be more deliberate in how you express yourself.
Another important issue is that online therapy is subject to less government oversight compared to the in-person approach, which is regulated in each state, providing a baseline of quality control. As a result, you have to do more research on the providers that offer online therapy to make sure they’re reputable, use only licensed therapists, and have a clear and transparent pay structure.
Be intentional about advocating for yourself
Figure out what kind of goals you want to achieve. Consider how, within the context of your goals, you can leverage the benefits of online therapy while addressing the weaknesses. Write down and commit to achieving your goals. Remember, you need to be your own advocate, especially in the less regulated space of online therapy, so focus on being proactive in achieving your goals.
Develop your Hero’s Journey
Because online therapy can occur at various times of day through videos calls, emails and text, it might feel more open-ended and less organized, which can have advantages and disadvantages. One way you can give it more structure is to ground these interactions in the story of your self-improvement. Our minds perceive the world through narratives. Create a story of how you’ll get from where you are to where you want to go, meaning your goals.
A good template to use is the Hero’s Journey. Start the narrative with where you are, and what caused you to seek therapy. Write about the obstacles you will need to overcome, and the kind of help from a therapist that you’ll need in the process. Then, describe the final end state: how will you be better off after this journey, including what you will have learned.
Especially in online therapy, you need to be on top of things. Too many people let the therapist manage the treatment plan. As you pursue your hero’s journey, another way to organize for success is to take notes on your progress, and reevaluate how you’re doing every month with your therapist.
Identify your ideal mentor
Since it’s more difficult to be confident about the quality of service providers in an online setting, you should identify in advance the traits of your desired therapist. Every Hero’s Journey involves a mentor figure who guides the protagonist through this journey. So who’s your ideal mentor? Write out their top 10 characteristics, from most to least important.
For example, you might want someone who is:
- Empathetic
- Caring
- Good listener
- Logical
- Direct
- Questioning
- Non-judgmental
- Organized
- Curious
- Flexible
That’s my list. Depending on what challenge you’re facing and your personality and preferences, you should make your own. Then, when you are matched with a therapist, evaluate how well they fit your ideal list.
Fail fast
When you first match with a therapist, try to fail fast. That means, instead of focusing on getting treatment, focus on figuring out if the therapist is a good match based on the traits you identified above. That will enable you to move on quickly if they’re not, and it’s very much worth it to figure that out early.
Tell them your goals, your story, and your vision of your ideal mentor. Ask them whether they think they are a match, and what kind of a treatment plan they would suggest based on the information you provided. And observe them yourself in your initial interactions, focusing on whether they’re a good match. Often, you’ll find that your initial vision of your ideal mentor is incomplete, and you’ll learn through doing therapy what kind of a therapist is the best fit for you.
Choose a small but meaningful subgoal to work on first
This small subgoal should be sufficient to be meaningful and impactful for improving your mental health, but not a big stretch for you to achieve. This subgoal should be a tool for you to use to evaluate whether the therapist is indeed a good fit for you. It will also help you evaluate whether the treatment plan makes sense, or whether it needs to be revised.
Know when to wrap things up
As you approach the end of your planned work and you see you’re reaching your goals, talk to the therapist about how to wrap up rather than letting things drag on for too long. You don’t want to become dependent on therapy: it’s meant to be a temporary intervention. Some less scrupulous therapists will insist that therapy should never end and we should all stay in therapy forever, and you want to avoid falling for this line. When you reach your goals, end your therapy, unless you discover a serious new reason to continue it. Still, it may be wise to set up occasional check-ins once every three to six months to make sure you’re staying on the right track.