Want to Strengthen American Democracy? The Science of Collaboration Can Help
The science of collaboration explores why diverse individuals choose to work together and how to design systems that encourage successful collaborations.
This article is part of the magazine, "The Future of Science In America: The Election Issue," co-published by LeapsMag, the Aspen Institute Science & Society Program, and GOOD.
American politics has no shortage of ailments. Many do not feel like their voice matters amid the money and influence amassed by corporations and wealthy donors. Many doubt whether elected officials and bureaucrats can or even want to effectively solve problems and respond to citizens' needs. Many feel divided both physically and psychologically, and uncomfortable (if not scared) at the prospect of building new connections across lines of difference.
Strengthening American democracy requires countering these trends. New collaborations between university researchers and community leaders such as elected officials, organizers, and nonprofit directors can help. These collaborations can entail everything from informal exchanges to co-led projects.
But there's a catch. They require that people with diverse forms of knowledge and lived experience, who are often strangers, choose to engage with one another. We know that strangers often remain strangers.
That's why a science of collaboration that centers the inception question is vital: When do diverse individuals choose to work together in the first place? How can we design institutions that encourage beneficial collaborations to arise and thrive? And what outcomes can occur?
How Collaborations Between Researchers and Community Leaders Can Help
First consider the feeling of powerlessness. Individual action becomes more powerful when part of a collective. For ordinary citizens, voting and organizing are arguably the two most impactful forms of collective action, and as it turns out there is substantial research on how to increase turnout and how to build powerful civic associations. Collaborations between researchers familiar with that work and organizers and nonprofit leaders familiar with a community's context can be especially impactful.
For example, in 2019, climate organizers with a nonpartisan group in North Carolina worked with a researcher who studies organizing to figure out how to increase volunteer commitment—that is, how to transform volunteers who only attend meetings into leaders who take responsibility for organizing others. Together, they designed strategies that made sense for the local area. Once implemented, these strategies led to a 161% year-over-year increase in commitment. More concretely, dozens of newly empowered volunteers led events to raise awareness of how climate change was impacting the local community and developed relationships with local officials and business owners, all while coming to see themselves as civic leaders. This experience also fed back into the researcher's work, motivating the design of future studies.
Or consider how researchers and local elected officials can collaborate and respond to novel challenges like the coronavirus. For instance, in March 2020, one county in Upstate New York suddenly had to figure out how to provide vital services like internet and health screenings for residents who could no longer visit shuttered county offices. They turned to a researcher who knew about research on mobile vans. Together, they spoke about the benefits and costs of mobile vans in general, and then segued into a more specific conversation about what routings and services would make sense in this specific locale. Their collaboration entailed a few conversations leading up to the county's decision, and in the end the county received helpful information and the researcher learned about new implementation challenges associated with mobile vans.
In April, legislators in another Upstate New York county realized they needed honest, if biting, feedback from local mayors about their response to the pandemic. They collaborated with researchers familiar with survey methodology. County legislators supplied the goals and historical information about fraught county–city relationships, while researchers supplied evidence-based techniques for conducting interviews in delicate contexts. These interviews ultimately revealed mayors' demand for more up-to-date coronavirus information from the county and also more county-led advocacy at the state level.
To be sure, there are many situations in which elected officials' lack of information is not the main hurdle. Rather, they need an incentive to act. Yet this is another situation in which collaborations between university researchers and community leaders focused on evidence-based, context-appropriate approaches to organizing and voter mobilization could produce needed pressure.
This brings me to the third way in which collaborations between researchers and community leaders can strengthen American democracy. They entail diverse people working to develop a common interest by building new connections across lines of difference. This is a core democratic skill that withers in the absence of practice.
In addition to credibility, we've learned that potential collaborators also care about whether others will be responsive to their goals and constraints, understand their point of view, and will be enjoyable to interact with.
The Science of Collaboration
The previous examples have one thing in common: a collaboration actually took place.
Yet that often does not happen. While there are many reasons why collaborations between diverse people should arise we know far less about when they actually do arise.
This is why a science of collaboration centered on inception is essential. Some studies have already revealed new insights. One thing we've learned is that credibility is important, but often not enough. By credibility, I mean that people are more likely to collaborate when they perceive each other to be trustworthy and have useful information or skills to share. Potential collaborators can signal their credibility by, for instance, identifying shared values and mentioning relevant previous experiences. One study finds that policymakers are more interested in collaborating with researchers who will share findings that are timely and locally relevant—that is, the kind that are most useful to them.
In addition to credibility, we've learned that potential collaborators also care about whether others will be responsive to their goals and constraints, understand their point of view, and will be enjoyable to interact with. For instance, potential collaborators can explicitly acknowledge that they know the other person is busy, or start with a question rather than a statement to indicate being interested. One study finds that busy nonprofit leaders are more likely to collaborate with researchers who explicitly state that (a) they are interested in learning about the leaders' expertise, and (b) they will efficiently share what they know. Another study underscores that potential collaborators need to feel like they know how to interact—that is, to feel like they have a "script" for what's appropriate to say during the interaction.
We're also learning that institutions (such as matchmaking organizations) can reduce uncertainty about credibility and relationality, and also help collaborations start off on the right foot. They are a critical avenue for connecting strangers. For instance, brokers can use techniques that increase the likelihood that diverse people feel comfortable sharing what they know, raising concerns, and being responsive to others.
Looking Ahead
A science of collaboration that centers the inception question is helpful on two levels. First, it provides an evidence base for how to effectively connect diverse people to work together. Second, when applied to university researchers and community leaders, it can produce collaborations that strengthen American democracy. Moreover, these collaborations are easily implemented, especially when informal and beginning as a conversation or two (as in the mobile vans example).
Existing research on the science of collaboration has already yielded actionable insights, yet we still have much to learn. For instance, we need to better understand the latent demand. Interviews that ask a wide variety of community leaders and researchers who have not previously collaborated to talk about why doing so might be helpful would be enlightening. They could also be a useful antidote to the narrative of conflict that often permeates discussions about the role of science in American politics.
In addition, we need to learn more about the downstream consequences of these collaborations, such as whether new networks arise that include colleagues of the initial collaborators. Here, it would be helpful to study the work of brokers – how they introduce people to each other, how much they follow up, and the impact of those decisions.
Ultimately, expanding the evidence base of the science of collaboration, and then directly applying what we learn, will provide important new and actionable avenues for strengthening American democracy.
[Editor's Note: To read other articles in this special magazine issue, visit the beautifully designed e-reader version.]
Questions remain about new drug for hot flashes
In May, a new drug, Fezolinetant, was approved by the FDA to treat hot flashes associated with menopause.
Vascomotor symptoms (VMS) is the medical term for hot flashes associated with menopause. You are going to hear a lot more about it because a company has a new drug to sell. Here is what you need to know.
Menopause marks the end of a woman’s reproductive capacity. Normal hormonal production associated with that monthly cycle becomes erratic and finally ceases. For some women the transition can be relatively brief with only modest symptoms, while for others the body's “thermostat” in the brain is disrupted and they experience hot flashes and other symptoms that can disrupt daily activity. Lifestyle modification and drugs such as hormone therapy can provide some relief, but women at risk for cancer are advised not to use them and other women choose not to do so.
Fezolinetant, sold by Astellas Pharma Inc. under the product name Veozah™, was approved by the Food and Drug Administration (FDA) on May 12 to treat hot flashes associated with menopause. It is the first in a new class of drugs called neurokinin 3 receptor antagonists, which block specific neurons in the brain “thermostat” that trigger VMS. It does not appear to affect other symptoms of menopause. As with many drugs targeting a brain cell receptor, it must be taken continuously for a few days to build up a good therapeutic response, rather than working as a rescue product such as an asthma inhaler to immediately treat that condition.
Hot flashes vary greatly and naturally get better or resolve completely with time. That contributes to a placebo effect and makes it more difficult to judge the outcome of any intervention. Early this year, a meta analysis of 17 studies of drug trials for hot flashes found an unusually large placebo response in those types of studies; the placebo groups had an average of 5.44 fewer hot flashes and a 36 percent reduction in their severity.
In studies of fezolinetant, the drug recently approved by the FDA, the placebo benefit was strong and persistent. The drug group bested the placebo response to a statistically significant degree but, “If people have gone from 11 hot flashes a day to eight or seven in the placebo group and down to a couple fewer ones in the drug groups, how meaningful is that? Having six hot flashes a day is still pretty unpleasant,” says Diana Zuckerman, president of the National Center for Health Research (NCHR), a health oriented think tank.
“Is a reduction compared to placebo of 2-3 hot flashes per day, in a population of women experiencing 10-11 moderate to severe hot flashes daily, enough relief to be clinically meaningful?” Andrea LaCroix asked a commentary published in Nature Medicine. She is an epidemiologist at the University of California San Diego and a leader of the MsFlash network that has conducted a handful of NIH-funded studies on menopause.
Questions Remain
LaCroix and others have raised questions about how Astellas, the company that makes the new drug, handled missing data from patients who dropped out of the clinical trials. “The lack of detailed information about important parameters such as adherence and missing data raises concerns that the reported benefits of fezolinetant very likely overestimate those that will be observed in clinical practice," LaCroix wrote.
In response to this concern, Anna Criddle, director of global portfolio communications at Astellas, wrote in an email to Leaps.org: “…a full analysis of data, including adherence data and any impact of missing data, was submitted for assessment by [the FDA].”
The company ran the studies at more than 300 sites around the world. Curiously, none appear to have been at academic medical centers, which are known for higher quality research. Zuckerman says, "When somebody is paid to do a study, if they want to get paid to do another study by the same company, they will try to make sure that the results are the results that the company wants.”
Criddle said that Astellas picked the sites “that would allow us to reach a diverse population of women, including race and ethnicity.”
A trial of a lower dose of the drug was conducted in Asia. In March 2022, Astellas issued a press release saying it had failed to prove effectiveness. No further data has been released. Astellas still plans to submit the data, according to Criddle. Results from clinical trials funded by the U.S. goverment must be reported on clinicaltrials.gov within one year of the study's completion - a deadline that, in this case, has expired.
The measurement scale for hot flashes used in the studies, mild-moderate-severe, also came in for criticism. “It is really not good scale, there probably isn’t a broad enough range of things going on or descriptors,” says David Rind. He is chief medical officer of the Institute for Clinical and Economic Review (ICER), a nonprofit authority on new drugs. It conducted a thorough review and analysis of fezolinestant using then existing data gathered from conference abstracts, posters and presentations and included a public stakeholder meeting in December. A 252-page report was published in January, finding “considerable uncertainty about the comparative net health benefits of fezolinetant” versus hormone therapy.
Questions surrounding some of these issues might have been answered if the FDA had chosen to hold a public advisory committee meeting on fezolinetant, which it regularly does for first in class medicines. But the agency decided such a meeting was unnecessary.
Cost
There was little surprise when Astellas announced a list price for fezolinetant of $550 a month ($6000 annually) and a program of patient assistance to ease out of pocket expenses. The company had already incurred large expenses.
In 2017 Astellas purchased the company that originally developed fezolinetant for $534 million plus several hundred million in potential royalties. The drug company ran a "disease awareness” ad, Heat on the Street, hat aired during the Super Bowl in February, where 30 second ads cost about $7 million. Industry analysts have projected sales to be $1.9 billion by 2028.
ICER’s pre-approval evaluation said fezolinetant might "be considered cost-effective if priced around $2,000 annually. ... [It]will depend upon its price and whether it is considered an alternative to MHT [menopause hormone treatment] for all women or whether it will primarily be used by women who cannot or will not take MHT."
Criddle wrote that Astellas set the price based on the novelty of the science, the quality of evidence for the drug and its uniqueness compared to the rest of the market. She noted that an individual’s payment will depend on how much their insurance company decides to cover. “[W]e expect insurance coverage to increase over the course of the year and to achieve widespread coverage in the U.S. over time.”
Leaps.org wrote to and followed up with nine of the largest health insurers/providers asking basic questions about their coverage of fezolinetant. Only two responded. Jennifer Martin, the deputy chief consultant for pharmacy benefits management at the Department of Veterans Affairs, said the agency “covers all drugs from the date that they are launched.” Decisions on whether it will be included in the drug formulary and what if any copays might be required are under review.
“[Fezolinetant] will go through our standard P&T Committee [patient and treatment] review process in the next few months, including a review of available efficacy data, safety data, clinical practice guidelines, and comparison with other agents used for vasomotor symptoms of menopause," said Phil Blando, executive director of corporate communications for CVS Health.
Other insurers likely are going through a similar process to decide issues such as limiting coverage to women who are advised not to use hormones, how much copay will be required, and whether women will be required to first try other options or obtain approvals before getting a prescription.
Rind wants to see a few years of use before he prescribes fezolinetant broadly, and believes most doctors share his view. Nor will they be eager to fill out the additional paperwork required for women to participate in the Astellas patient assistance program, he added.
Safety
Astellas is marketing its drug by pointing out risks of hormone therapy, such as a recent paper in The BMJ, which noted that women who took hormones for even a short period of time had a 24 percent increased risk of dementia. While the percentage was scary, the combined number of women both on and off hormones who developed dementia was small. And it is unclear whether hormones are causing dementia or if more severe hot flashes are a marker for higher risk of developing dementia. This information is emerging only after 80 years of hundreds of millions of women using hormones.
In contrast, the label for fezolinetant prohibits “concomitant use with CYP1A2 inhibitors” and requires testing for liver and kidney function prior to initiating the drug and every three months thereafter. There is no human or animal data on use in a geriatric population, defined as 65 or older, a group that is likely to use the drug. Only a few thousand women have ever taken fezolinetant and most have used it for just a few months.
Options
A woman seeking relief from symptoms of menopause would like to see how fezolintant compares with other available treatment options. But Astellas did not conduct such a study and Andrea LaCroix says it is unlikely that anyone ever will.
ICER has come the closest, with a side-by-side analysis of evidence-based treatments and found that fezolinetant performed quite similarly and modestly as the others in providing relief from hot flashes. Some treatments also help with other symptoms of menopause, which fezolinetant does not.
There are many coping strategies that women can adopt to deal with hot flashes; one of the most common is dressing in layers (such as a sleeveless blouse with a sweater) that can be added or subtracted as conditions require. Avoiding caffeine, hot liquids, and spicy foods is another common strategy. “I stopped drinking hot caffeinated drinks…for several years, and you get out of the habit of drinking them,” says Zuckerman.
LaCroix curates those options at My Meno Plan, which includes a search function where you can enter your symptoms and identify which treatments might work best for you. It also links to published research papers. She says the goal is to empower women with information to make informed decisions about menopause.
A company in England has made a test that picks out the compounds from breath that reveal if people have liver disease.
Every year, around two million people worldwide die of liver disease. While some people inherit the disease, it’s most commonly caused by hepatitis, obesity and alcoholism. These underlying conditions kill liver cells, causing scar tissue to form until eventually the liver cannot function properly. Since 1979, deaths due to liver disease have increased by 400 percent.
The sooner the disease is detected, the more effective treatment can be. But once symptoms appear, the liver is already damaged. Around 50 percent of cases are diagnosed only after the disease has reached the final stages, when treatment is largely ineffective.
To address this problem, Owlstone Medical, a biotech company in England, has developed a breath test that can detect liver disease earlier than conventional approaches. Human breath contains volatile organic compounds (VOCs) that change in the first stages of liver disease. Owlstone’s breath test can reliably collect, store and detect VOCs, while picking out the specific compounds that reveal liver disease.
“There’s a need to screen more broadly for people with early-stage liver disease,” says Owlstone’s CEO Billy Boyle. “Equally important is having a test that's non-invasive, cost effective and can be deployed in a primary care setting.”
The standard tool for detection is a biopsy. It is invasive and expensive, making it impractical to use for people who aren't yet symptomatic. Meanwhile, blood tests are less invasive, but they can be inaccurate and can’t discriminate between different stages of the disease.
In the past, breath tests have not been widely used because of the difficulties of reliably collecting and storing breath. But Owlstone’s technology could help change that.
The team is testing patients in the early stages of advanced liver disease, or cirrhosis, to identify and detect these biomarkers. In an initial study, Owlstone’s breathalyzer was able to pick out patients who had early cirrhosis with 83 percent sensitivity.
Boyle’s work is personally motivated. His wife died of colorectal cancer after she was diagnosed with a progressed form of the disease. “That was a big impetus for me to see if this technology could work in early detection,” he says. “As a company, Owlstone is interested in early detection across a range of diseases because we think that's a way to save lives and a way to save costs.”
How it works
In the past, breath tests have not been widely used because of the difficulties of reliably collecting and storing breath. But Owlstone’s technology could help change that.
Study participants breathe into a mouthpiece attached to a breath sampler developed by Owlstone. It has cartridges are designed and optimized to collect gases. The sampler specifically targets VOCs, extracting them from atmospheric gases in breath, to ensure that even low levels of these compounds are captured.
The sampler can store compounds stably before they are assessed through a method called mass spectrometry, in which compounds are converted into charged atoms, before electromagnetic fields filter and identify even the tiniest amounts of charged atoms according to their weight and charge.
The top four compounds in our breath
In an initial study, Owlstone captured VOCs in breath to see which ones could help them tell the difference between people with and without liver disease. They tested the breath of 46 patients with liver disease - most of them in the earlier stages of cirrhosis - and 42 healthy people. Using this data, they were able to create a diagnostic model. Individually, compounds like 2-Pentanone and limonene performed well as markers for liver disease. Owlstone achieved even better performance by examining the levels of the top four compounds together, distinguishing between liver disease cases and controls with 95 percent accuracy.
“It was a good proof of principle since it looks like there are breath biomarkers that can discriminate between diseases,” Boyle says. “That was a bit of a stepping stone for us to say, taking those identified, let’s try and dose with specific concentrations of probes. It's part of building the evidence and steering the clinical trials to get to liver disease sensitivity.”
Sabine Szunerits, a professor of chemistry in Institute of Electronics at the University of Lille, sees the potential of Owlstone’s technology.
“Breath analysis is showing real promise as a clinical diagnostic tool,” says Szunerits, who has no ties with the company. “Owlstone Medical’s technology is extremely effective in collecting small volatile organic biomarkers in the breath. In combination with pattern recognition it can give an answer on liver disease severity. I see it as a very promising way to give patients novel chances to be cured.”
Improving the breath sampling process
Challenges remain. With more than one thousand VOCs found in the breath, it can be difficult to identify markers for liver disease that are consistent across many patients.
Julian Gardner is a professor of electrical engineering at Warwick University who researches electronic sensing devices. “Everyone’s breath has different levels of VOCs and different ones according to gender, diet, age etc,” Gardner says. “It is indeed very challenging to selectively detect the biomarkers in the breath for liver disease.”
So Owlstone is putting chemicals in the body that they know interact differently with patients with liver disease, and then using the breath sampler to measure these specific VOCs. The chemicals they administer are called Exogenous Volatile Organic Compound) probes, or EVOCs.
Most recently, they used limonene as an EVOC probe, testing 29 patients with early cirrhosis and 29 controls. They gave the limonene to subjects at specific doses to measure how its concentrations change in breath. The aim was to try and see what was happening in their livers.
“They are proposing to use drugs to enhance the signal as they are concerned about the sensitivity and selectivity of their method,” Gardner says. “The approach of EVOC probes is probably necessary as you can then eliminate the person-to-person variation that will be considerable in the soup of VOCs in our breath.”
Through these probes, Owlstone could identify patients with liver disease with 83 percent sensitivity. By targeting what they knew was a disease mechanism, they were able to amplify the signal. The company is starting a larger clinical trial, and the plan is to eventually use a panel of EVOC probes to make sure they can see diverging VOCs more clearly.
“I think the approach of using probes to amplify the VOC signal will ultimately increase the specificity of any VOC breath tests, and improve their practical usability,” says Roger Yazbek, who leads the South Australian Breath Analysis Research (SABAR) laboratory in Flinders University. “Whilst the findings are interesting, it still is only a small cohort of patients in one location.”
The future of breath diagnosis
Owlstone wants to partner with pharmaceutical companies looking to learn if their drugs have an effect on liver disease. They’ve also developed a microchip, a miniaturized version of mass spectrometry instruments, that can be used with the breathalyzer. It is less sensitive but will enable faster detection.
Boyle says the company's mission is for their tests to save 100,000 lives. "There are lots of risks and lots of challenges. I think there's an opportunity to really establish breath as a new diagnostic class.”