Too Many Vaccine Trials May Exclude Older Adults - The New York Times

thekflow.blogspot.com

Picture the day — in six months, a year and a half or in 2023 — when university researchers or a pharmaceutical company announces a breakthrough against the virus that causes Covid-19.

Maybe it’s a successful vaccine or an effective treatment, a discovery that brings hope and relief — especially to the older adults most vulnerable to the disease, eager to return to their pre-pandemic lives.

Imagine, however, that the researchers neglected to enroll many people in their 70s or 80s in the clinical trials that established the effectiveness of this treatment. As a result, it’s unclear how much the treatment will benefit older people, what risks it might pose, or if the dose that works for younger people is the best one for an older population.

Could that really happen? Certainly there is a long history of older people being excluded from clinical trials, even when the diseases in question disproportionately affected this group. They have been underrepresented, for instance, in studies of heart disease, cancer, diabetes and osteoporosis.

“Ideally, the patients enrolled in a randomized clinical trial reflect the demographics of the disease,” said Dr. Mark Sloan, a hematologist leading a Covid-19 drug study at Boston Medical Center, in an email. “Unfortunately, this is seldom the case.”

Now, Dr. Sharon K. Inouye, a geriatrician at Harvard Medical School and Hebrew SeniorLife, is sounding an alarm. She points out that in the race to find drugs and vaccines to fight the pandemic — in which 80 percent of American deaths have occurred in people over age 65 — a substantial proportion of studies may be excluding older subjects, purposely or inadvertently.

“A year from now, when these trials are published, I don’t want to see that there’s no one in them over 75,” she said. “If they create a drug that works really well in healthy 50- and 60-year-olds, they’ve missed the boat.”

She and her team have reviewed 241 interventional Covid-19 studies undertaken in the United States and listed on clinicaltrials.gov, a site maintained by a division of the National Institutes of Health.

They found that 37 of these trials — testing drugs, vaccines and devices — set specific age limits and would not enroll participants older than 75, 80 or 85. A few even excluded those over 65.

Another group of 27 trials set no maximum age but used study designs that could nevertheless disqualify many older adults.

Some excluded people with illnesses common among the older population, like hypertension or diabetes, even if participants controlled the disease through medication. “Surrogates for age exclusion,” Dr. Inouye said.

In other cases, broad exclusion criteria gave the investigator inordinate discretion. Dr. Inouye pointed to one trial barring subjects with “any physical examination findings, and/or history of any illness, concomitant medications or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the participant.”

That allows investigators to exclude people for reasons ranging from legitimate safety issues to the researchers’ own convenience. One scenario that worried Dr. Inouye: “If you have an older adult who appears hard of hearing, and it takes twice as long to explain the study and obtain consent, the investigator just won’t do it.”

Other studies, relying on digital technology, might rule out people who lack smartphones or the ability to use email.

Overall, when Dr. Inouye compiled preliminary results, which have not yet been published, she found that about one-quarter of interventional trials in the United States could exclude or underrepresent older adults.

“To have them be this gravely impacted and not include them is immoral,” said Dr. Louise Aronson, the author of the best-selling book “Elderhood” and a geriatrician at the University of California, San Francisco. “It seems crazy.”

In response to similar concerns, the N.I.H. began last year to require the studies it funds to include “individuals across the life span,” unless investigators provide an “acceptable justification” for exclusion. If they cannot, N.I.H. won’t award the grants.

“It’s a pretty visible guidepost, reflecting national standards,” Dr. Aronson said. But most clinical trials are privately funded and need not follow N.I.H. policy.

Although Dr. Inouye systematically reviewed only American trials, her team also noticed age limits in Covid-19 studies in France, Italy, China, Colombia and other countries, some set as low as age 60.

Whether such trials will actually exclude many older subjects probably will not be clear for some time. Several investigators, asked about the number of enrolled participants over age 80, said they were only starting recruitment or could not yet provide data.

Some investigators might make accommodations. A study at the University of California, San Francisco, for example, examining the use of the antibiotic azithromycin, drew Dr. Inouye’s attention because participants had to submit questionnaires online. But Catherine Oldenburg, a co-principal investigator, explained in an email that researchers would also allow participants to complete interviews by phone or have a proxy submit the online forms.

Still, the rush to learn more about the deadly coronavirus could exacerbate the problem, because including older people can make research slower, more complicated and more expensive.

The Coronavirus Outbreak

• Frequently Asked Questions and Advice

  Updated June 16, 2020

  • I’ve heard about a treatment called dexamethasone. Does it work?

    The steroid, dexamethasone, is the first treatment shown to reduce mortality in severely ill patients, according to scientists in Britain. The drug appears to reduce inflammation caused by the immune system, protecting the tissues. In the study, dexamethasone reduced deaths of patients on ventilators by one-third, and deaths of patients on oxygen by one-fifth.

  • What is pandemic paid leave?

    The coronavirus emergency relief package gives many American workers paid leave if they need to take time off because of the virus. It gives qualified workers two weeks of paid sick leave if they are ill, quarantined or seeking diagnosis or preventive care for coronavirus, or if they are caring for sick family members. It gives 12 weeks of paid leave to people caring for children whose schools are closed or whose child care provider is unavailable because of the coronavirus. It is the first time the United States has had widespread federally mandated paid leave, and includes people who don’t typically get such benefits, like part-time and gig economy workers. But the measure excludes at least half of private-sector workers, including those at the country’s largest employers, and gives small employers significant leeway to deny leave.

  • Does asymptomatic transmission of Covid-19 happen?

    So far, the evidence seems to show it does. A widely cited paper published in April suggests that people are most infectious about two days before the onset of coronavirus symptoms and estimated that 44 percent of new infections were a result of transmission from people who were not yet showing symptoms. Recently, a top expert at the World Health Organization stated that transmission of the coronavirus by people who did not have symptoms was “very rare,” but she later walked back that statement.

  • What’s the risk of catching coronavirus from a surface?

    Touching contaminated objects and then infecting ourselves with the germs is not typically how the virus spreads. But it can happen. A number of studies of flu, rhinovirus, coronavirus and other microbes have shown that respiratory illnesses, including the new coronavirus, can spread by touching contaminated surfaces, particularly in places like day care centers, offices and hospitals. But a long chain of events has to happen for the disease to spread that way. The best way to protect yourself from coronavirus — whether it’s surface transmission or close human contact — is still social distancing, washing your hands, not touching your face and wearing masks.

  • How does blood type influence coronavirus?

    A study by European scientists is the first to document a strong statistical link between genetic variations and Covid-19, the illness caused by the coronavirus. Having Type A blood was linked to a 50 percent increase in the likelihood that a patient would need to get oxygen or to go on a ventilator, according to the new study.

  • How many people have lost their jobs due to coronavirus in the U.S.?

    The unemployment rate fell to 13.3 percent in May, the Labor Department said on June 5, an unexpected improvement in the nation’s job market as hiring rebounded faster than economists expected. Economists had forecast the unemployment rate to increase to as much as 20 percent, after it hit 14.7 percent in April, which was the highest since the government began keeping official statistics after World War II. But the unemployment rate dipped instead, with employers adding 2.5 million jobs, after more than 20 million jobs were lost in April.

  • Will protests set off a second viral wave of coronavirus?

    Mass protests against police brutality that have brought thousands of people onto the streets in cities across America are raising the specter of new coronavirus outbreaks, prompting political leaders, physicians and public health experts to warn that the crowds could cause a surge in cases. While many political leaders affirmed the right of protesters to express themselves, they urged the demonstrators to wear face masks and maintain social distancing, both to protect themselves and to prevent further community spread of the virus. Some infectious disease experts were reassured by the fact that the protests were held outdoors, saying the open air settings could mitigate the risk of transmission.

  • My state is reopening. Is it safe to go out?

    States are reopening bit by bit. This means that more public spaces are available for use and more and more businesses are being allowed to open again. The federal government is largely leaving the decision up to states, and some state leaders are leaving the decision up to local authorities. Even if you aren’t being told to stay at home, it’s still a good idea to limit trips outside and your interaction with other people.

  • What are the symptoms of coronavirus?

    Common symptoms include fever, a dry cough, fatigue and difficulty breathing or shortness of breath. Some of these symptoms overlap with those of the flu, making detection difficult, but runny noses and stuffy sinuses are less common. The C.D.C. has also added chills, muscle pain, sore throat, headache and a new loss of the sense of taste or smell as symptoms to look out for. Most people fall ill five to seven days after exposure, but symptoms may appear in as few as two days or as many as 14 days.

  • How can I protect myself while flying?

    If air travel is unavoidable, there are some steps you can take to protect yourself. Most important: Wash your hands often, and stop touching your face. If possible, choose a window seat. A study from Emory University found that during flu season, the safest place to sit on a plane is by a window, as people sitting in window seats had less contact with potentially sick people. Disinfect hard surfaces. When you get to your seat and your hands are clean, use disinfecting wipes to clean the hard surfaces at your seat like the head and arm rest, the seatbelt buckle, the remote, screen, seat back pocket and the tray table. If the seat is hard and nonporous or leather or pleather, you can wipe that down, too. (Using wipes on upholstered seats could lead to a wet seat and spreading of germs rather than killing them.)

  • How do I take my temperature?

    Taking one’s temperature to look for signs of fever is not as easy as it sounds, as “normal” temperature numbers can vary, but generally, keep an eye out for a temperature of 100.5 degrees Fahrenheit or higher. If you don’t have a thermometer (they can be pricey these days), there are other ways to figure out if you have a fever, or are at risk of Covid-19 complications.

  • Should I wear a mask?

    The C.D.C. has recommended that all Americans wear cloth masks if they go out in public. This is a shift in federal guidance reflecting new concerns that the coronavirus is being spread by infected people who have no symptoms. Until now, the C.D.C., like the W.H.O., has advised that ordinary people don’t need to wear masks unless they are sick and coughing. Part of the reason was to preserve medical-grade masks for health care workers who desperately need them at a time when they are in continuously short supply. Masks don’t replace hand washing and social distancing.

  • What should I do if I feel sick?

    If you’ve been exposed to the coronavirus or think you have, and have a fever or symptoms like a cough or difficulty breathing, call a doctor. They should give you advice on whether you should be tested, how to get tested, and how to seek medical treatment without potentially infecting or exposing others.

  • How do I get tested?

    If you’re sick and you think you’ve been exposed to the new coronavirus, the C.D.C. recommends that you call your healthcare provider and explain your symptoms and fears. They will decide if you need to be tested. Keep in mind that there’s a chance — because of a lack of testing kits or because you’re asymptomatic, for instance — you won’t be able to get tested.

---

In clinical trials, “you want to control as many factors as possible,” Dr. Aronson said. Most older adults have other illnesses and take multiple medications, so-called confounding variables that make it difficult to distinguish the effects of the drug or vaccine being studied.

Older people also suffer more side effects. “Nearly all drugs are less toxic when given to younger, healthier people,” Dr. Sloan said in an email. Focusing on them produces fewer adverse effects that must be reported, “and thereby improves chances for F.D.A. approval.”

Physical disabilities, which make it harder for seniors to reach study sites, or hearing and vision impairments requiring large-print forms or audio amplification, can further decrease participation. Investigators may need to take the extra step of obtaining family consent if a patient is incapacitated.

“The same things that put you at higher risk for Covid make it harder to study you,” Dr. Aronson said.

But that shouldn’t prevent researchers from incorporating the population most at risk from the coronavirus. “If that’s the real-world scenario, you’ve got to deal with it,” said Susan Peschin, the president of the nonprofit Alliance for Aging Research.

The Alliance wants the F.D.A., which is now preparing guidance for including older adults in cancer research, to issue guidelines covering all medical products for conditions that primarily impact the elderly.

The F.D.A. has issued this kind of guidance as far back as 1993, and it released additional guidelines in 2012 and again last year, said Dr. Harpreet Singh, a division director at the agency’s Oncology Center of Excellence — although such guidance is not legally binding or enforceable.

Dr. Singh, a geriatrician and oncologist, acknowledged in an interview that the agency could do more to promote the inclusion of seniors. And when there is reason to suspect that trials are overlooking them, “it should be called out and examined.”

That’s what Dr. Inouye has undertaken, although she worries that she may be too late. Covid-19 studies already underway can still revamp their criteria to include older participants — there are reliable strategies to achieve that — but investigators are working at an accelerated pace, under great pressure to produce results.

For researchers, the professional and financial stakes are high. But they are even higher for older Americans.

“These are the people getting very ill from Covid and dying from it,” Dr. Inouye said. “If people are genuinely committed to inclusion, let’s do what we need to do.”

Let's block ads! (Why?)

"may" - Google News
June 19, 2020 at 09:23PM
https://ift.tt/3dfxvYR

Too Many Vaccine Trials May Exclude Older Adults - The New York Times
"may" - Google News
https://ift.tt/3foH8qu
https://ift.tt/2zNW3tO

Bagikan Berita Ini