JustCare

Tag: Clinical trials

  • Beware experimental Alzheimer’s drug trials

    Beware experimental Alzheimer’s drug trials

    Melody Peterson reports for the LA TImes on how pharmaceutical companies enlist Californians with Medicare to participate in a clinical trial for experimental drugs intended to stave off Alzheimer’s. Ads promote drug trials for people who are losing their memories, as a way to keep their minds sharp. But, participating in an experimental Alzheimer’s drug trial carries serious risks.

    The pharmaceutical companies see Alzheimer’s drugs as a mega-opportunity to generate outsized profits. The six million-person market is huge and only growing. There’s little limit on what pharmaceutical companies can charge for these drugs. And, if FDA-approved, Medicare must cover them when medically reasonable and necessary.

    Already, the FDA has approved Aduhelm and Leqembi, which costs $26,000 a year, even though neither drug shows significant benefits and both can have serious side effects. Now, the race is on for pharmaceutical companies to market other drugs. But, the pharmaceutical companies need nearly 60,000 individuals to participate in the clinical trials of the 140 drugs being developed that are still experimental. 

    No question that if an Alzheimer’s drug works well, it could improve and extend the lives of people with Alzheimer’s and, arguably, save the health care system money as well. But, the clinical trials are not designed to treat people, only to test a drug’s efficacy. In fact, the trials can severely harm people.

    Some believe the Leqembi trials were responsible for the death of three people, though the drug’s manufacturer claims Leqembi was not likely the cause of their deaths. Four in ten participants in the Aduhelm trials experienced brain bleeding or swelling.

    Do trial participants understand that these experimental drugs come with a risk of brain swelling or bleeding? Is there a financial conflict of interest for the trial investigators who could make big money from the experimental drugs when they recruit trial participants? Do they overpromise?

    One recruiter offers older adults free meals and health tips. Pharmaceutical companies pay for the costs of recruitment activities. Then, their agents get people who are interested in participating in a clinical trial to sign a long consent form.

    But, how can you expect people who are struggling with memory issues to understand the consent form? They’re likely unaware of what they are signing. For that reason, federal regulations forbid people’s enrollment in a clinical trial if they lack the mental ability to understand a consent form, unless someone who has the legal authority to consent on their behalf does so.

    But, the clinical trial recruitment team is not required to have an independent monitor overseeing recruitment activities. And, it is not in their interest financially to ensure that the people they recruit have the ability to understand a consent form. The recruiters generally receive between $40,000 and $75,000 for every person they recruit to participate in a trial.

    What’s equally concerning is that the FDA can approve a drug like Leqembi, even when, based on the findings, experts question whether its benefits are meaningful. When a pharmaceutical company invests in a clinical trial, it does not need to release information on the results. To hide the results when they do not appear favorable, the pharmaceutical company can simply stop the trial.

    Here’s more from Just Care:

  • Medicare won’t cover Alzheimer’s drug, except in clinical trials

    Medicare won’t cover Alzheimer’s drug, except in clinical trials

    Once in a while, the government prevails against drugmakers. Last Thursday, the Centers for Medicare and Medicaid Services (CMS) decided it would not cover the controversial Alzheimer’s drug, Aduhelm, except in clinical trials, despite the FDA’s approval of the drug. In an opinion piece for Stat News, John N. Mafi and Catherine Sarkisian, professors of medicine at UCLA, explain why it is appropriate that Medicare will only cover the drug for people participating in clinical trials.

    Physicians and scientists have applauded CMS’ decision. Aduhelm has unclear benefits and presents huge risks. But, not surprisingly, Wall Street went ballistic on hearing the decision. Biogen threatened to sue CMS. While the cost of the drug is astronomical and reason enough to question whether it should be covered, the danger to people’s health and well-being from taking the drug are real and serious.

    No one can argue that Aduhelm is either safe or effective, based on the evidence. More than four in ten people who took the drug ended up with bleeding or swelling in the brain. On top of that, one in fifty people lost their vision permanently. Other dangerous side effects are not yet known.

    In addition, clinical trials at best show a possible benefit from the drug and many trials show no improved memory. The possible benefit was determined only in retrospective analysis, where there is a high likelihood of false positives. Moreover, the clinical trials were not conducted on an ethnically or racially diverse population.

    Medicare is not allowed to factor in the cost of a drug when deciding whether to cover it. But, it should not pay for a drug that has no proven value and proven risks. The Medicare trust fund is predicted to be insolvent by 2026. At its initial launch price of $56,000, the drug would drive up costs for a Medicare population already struggling to afford needed care. It added $11 to the monthly Part B premium this year. People taking Aduhelm would spend about $6,800 a year, more than a quarter of their typical income, out of pocket.

    Those arguing for Medicare’s coverage of the drug falsely claim that it will keep other drugs from being developed. There’s too much money in drug development, and drugmakers know that CMS’ decision is the exception, not the rule. Moreover, CMS has previously opted not to cover an FDA-approved drug.

    Thank goodness CMS did not agree to cover Aduhelm at this time. That should lead to a lower Part B premium in the not too distant future.

    Here’s more from Just Care:

  • Clinical trials need to include more older adults

    Clinical trials need to include more older adults

    Older adults have historically been excluded from clinical trials that test new drug treatments, even though older adults are most likely to need these treatments. Pratibha Gopalakrishna reports for StatNews that the problem continues. Even most reported Phase 3 COVID-19 clinical trials do not include older adults.

    Treatments should be developed with the needs of older Americans in mind, both in a pandemic and more broadly. Older adults have higher disease rates than younger people. The disproportionate number of deaths of older adults during this pandemic illustrates just how hard hit older adults can be from a transmissible disease.

    When older adults are not included in a clinical trial, it is much harder to know whether a drug will work for them, how safe the drug is, what the side effects might be, or how high a dosage they need. They might react very differently to a drug than a younger person.

    In January 2019, the National Institutes of Health released the Inclusion Across the Lifespan Policy. It requires that researchers include older people as well as younger people in their trials, if they are using NIH funding, unless there is a scientific or ethical reason not to. But, at least with cardiovascular trials that have taken place since this new policy, one in three trials still had age limits.

    In addition, some cardiovascular trials studied used exclusion criteria that were not age-specific. But, these criteria excluded people with pre-existing conditions, which includes most older adults. And, most studies were not looking to see whether a treatment benefited older adults.

    Perhaps, over time, the new NIH policy will bear fruit and do more to ensure new treatments are tested with older adults in mind. But, some experts say that a lot of the research is done on participants who are much younger on average than the age of people with serious diseases.

    Of course, in some cases, it may be perfectly appropriate to exclude older people from a trial because of risks of drug interactions, as well as compliance concerns, or inability to consent to the study. On top of these challenges to including older adults in clinical trials, there are challenges with identifying and recruiting older adult participants, along with transportation challenges.

    Here’s more from Just Care:

  • Warning: Your hip replacement could kill you

    Warning: Your hip replacement could kill you

    Jeanne Lenzer writes for the New York Times about the danger of getting a hip replacement. In some cases, your hip replacement could cause serious harm. In general, as we have reported, FDA-approved medical devices may not be safe.

    Stephen Tower, an orthopedic surgeon, had a metal-on-metal hip implanted, the ASR XL, made by Johnson & Johnson. Dr. Tower specializes in complex hip replacements, but he was not aware that the hip he chose for himself had a serious defect. He ended up needing another surgery because of the pain his artificial hip was causing him.

    Dr. Tower’s artificial hip had turned the tissue around it black. The artificial hip leaked cobalt causing Dr. Tower to suffer from metallosis. Muscles, tendons and ligaments near the hip were destroyed. Worse still, Dr. Tower suffered damage to his heart and brain.

    Afterwards, Dr. Tower warned Johnson & Johnson of the serious defect in the hip but the medical device company did nothing about it. Rather, it continued to market metal-on-metal hips. It finally withdrew the ASR XL model from the market in 2010, but it sold another metal-on-metal hip, the Pinnacle, until 2013.

    Thousands of people received a Johnson & Johnson metal-on-metal hip replacement during this time. Six of them won a $247 million verdict because of the Pinnacle’s harmful side effects and because Johnson & Johnson did not warn doctors or patients about these side effects.

    Unfortunately, these metal-on-metal hips are one of many FDA-approved medical devices on the market that put patients at risk for dangerous side effects.  A provision of the Federal Food, Drug and Cosmetic Act, known as 510(k), allows medical device companies to market many new products without having to do any clinical trials. All that the medical device company need do is claim that the device is “substantially equivalent” to a medical device already on the market.

    While the FDA can recall the product if it is deemed to cause harm, it can take a long time for that recall to happen. Hundreds of thousands of people can end with the device implanted before it is recalled. And removal of the device once recalled can also jeopardize patients’ health.

    In 2016 alone, the FDA recalled 117 medical devices because of a “reasonable probability” that they would “cause serious adverse health consequences or death.”

    Medical devices that undergo clinical trials are also not guaranteed to be risk free. Indeed, the FDA may conditionally approve them even when the clinical trials show potentially harmful side effects, including a high death rate. That’s what happened with a Cyberonics device designed to treat epilepsy. The FDA did not require that patients who received this device be told about the risk of dangerous side effects.

    The FDA’s approval process appears to put profits before patients. Yes, more devices get to market more quickly. But, at what cost to human life and health?

    Here’s more from Just Care:

  • Do new cancer treatments offer meaningful benefits?

    Do new cancer treatments offer meaningful benefits?

    Stat News reports on a new study, published in BMJ, which finds that around 50 percent of the clinical trials for cancer treatments approved in Europe may not demonstrate meaningful benefits. Risk of bias in the design and reporting of clinical trials may mean that the drugs lack both therapeutic and financial value. Studies of clinical trials for cancer drugs approved in the US have similar flaws.

    For the BMJ study, researchers looked at the strength of the evidence supporting new cancer drug approvals in Europe. They analyzed 54 clinical trials for the 32 cancer drugs approved between 2014 and 2016. Of those with published studies, only one in four looked at overall survival rates. All the other trials, 29 out of 39, used “surrogate measures.” Surrogate measures cannot predict whether someone will live longer or enjoy a better quality of life. Some academics say they may undermine patient safety.

    Researchers found that just about half (49 percent) of the published trials had a high risk of bias. They found a much higher risk of bias in the trials looking at surrogate measures of patient benefit (55 percent) than in the trials measuring overall survival (20 percent). Note: Researchers found risk of bias, not actual bias.

    Only 75 percent of the drug studies (41 of them) from 2014 to 2016 involved randomized, controlled trials. Just 27 of the 32 newly approved cancer drugs had a randomized trial. Between, 2009 and 2013, 90 percent of the studies involved randomized, controlled trials.

    In addition, of the 32 drugs approved, 10 had problems identified by regulators. But, somehow, the regulators’ concerns about these drugs did not make it into the scientific literature.

    The researchers recommend that clinical research for drugs be based on randomized trials and that these trials study data on meaningful outcomes, specifically overall survival. Without this research, it is hard to know whether new cancer drugs meet patients’ needs. It’s best to have a quality assessment of the evidence as well. Bias in clinical trial design is a serious issue.

    The researchers also want more transparency from regulators. Patients should know the weaknesses of the research underlying a new drug and how these weaknesses might affect the trial results.

    Here’s more from Just Care:

  • How to ensure the drugs you take are safe and effective

    How to ensure the drugs you take are safe and effective

    Drugs recently approved by the Food and Drug Administration–within the last ten years–may turn out not to be safe or effective. How can this be? And, how can you ensure the drugs you take are safe and effective?

    To be clear, the FDA only approves drugs that it finds to be safe and effective.  But, it bases its approval on limited data. So, what might appear to be safe and effective at the drug approval stage, may turn out not to be. One in seven older adults experience harmful drug side effects.

    To get a drug approved, pharmaceutical companies must conduct clinical trials or lab tests that show the drug is safe and works better than a placebo, essentially a sugar pill or nothing. But, clinical trials are usually performed on a small cohort of people, a tiny fraction of the number of people who will end up taking the drug. Often the people in the clinical trials are not elderly or children or otherwise like the people who are prescribed the drug. As a result, in the real world, outside of the clinical trials setting, the drug may be ineffective or, worse still, dangerous for some people who take it. Drug safety is a big issue.

    Sometimes, a drug’s potentially dangerous side effects may only become evident after six months or a year of a person taking it. But, a clinical trial may last for only six months. And, about 10 percent of the time, a drug may be prescribed for off-label use. When prescribed off-label, for a different condition from which it was tested, people may experience dangerous side effects. Keep in mind, as well, that peer-reviewed papers showing the value of the drug for a particular condition, may be biased. Too often the papers’ authors have financial ties to the drug industry.

    Unfortunately, the FDA does not do the job it needs to do monitoring drugs after they are approved and publicly reporting their side effects. Indeed, because it is very hard to prove that people’s side effects stem from a particular drug, drugs with dangerous side effects may not be pulled from the market for many years. Even warnings about these side effects may not be published.

    What can you do? 

    1.  Choose your doctors carefully. Make sure that your doctors listen to you and take the time to know you.
    2. At each doctor’s visit, question whether you still need to be taking the prescription drugs your doctor has prescribed or whether it is possible to stop taking one or more of them.
    3. Check to see whether your doctor is taking money from drug companies on Dollars for Docs. If so, consider talking to your doctor about that in connection with the drugs your doctor has prescribed for you.
    4. If there’s a generic substitute for the drugs you take or a lower-cost alternative, ask your about switching to that drug.
    5. If a drug you are taking was recently approved by the FDA, ask about side effects and whether there is an older drug you could be taking instead. With an older drug, you have a better sense of the drug’s safety and usually pay less for it.

    Ironically, the FDA does not allow people to import drugs for personal use for “safety” reasons. That said, Kaiser Health News reports that 19 million Americans import drugs from abroad every year. No one has ever reported a safety issue from prescribed drugs bought from a verified pharmacy abroad. Indeed, by some counts 70 percent of the drugs we take in the US were manufactured abroad.

    Here’s more from Just Care:

  • Drug companies must now disclose most clinical trial results

    Drug companies must now disclose most clinical trial results

    For years, drug and medical device companies have been able to conduct clinical trials and then, depending upon results, determine which ones to make public. They were not required to let the public know about poor outcomes of clinical trials, even for a drug receiving FDA approval based on a different clinical trial with a beneficial outcome. Now, these companies must disclose most clinical trial results, even if they show a drug or device may not be safe or effective.

    The U.S. Department of Health and Human Services has issued a final rule expanding the conditions under which pharmaceutical companies, medical device companies and manufacturers of biologics must register clinical trials and disclose summary results information on ClinicalTrials.gov, including information about harmful side effects.  The National Institutes of Health has issued a policy that complements the HHS policy for registering and disclosing summary results information on ClinicalTrials.gov for all NIH-funded trials, including trials that are not subject to the HHS final rule.

    NIH Director Francis S. Collins, M.D. said that he wanted to make sure the public got maximum value from clinical trials, whether funded with government money or private money. “Access to more information about clinical trials is good for patients, the public and science.”

    The goal of clinical trials is to ensure that health care drugs and devices are safe and effective. They sometimes also indicate when one medical treatment is better for a specific condition or particular subpopulation (e.g., children, older adults) than another.

    These new requirements should make it easier for people to learn about clinical trials in which they might be interested in participating as well as new possible treatments for their conditions. And, more information about clinical results will enable patients and doctors to make more informed decisions about appropriate treatments. It will also help researchers design studies based on more information about clinical trial results.

    The HHS final rule requires companies to register and disclose summary results for trials of most products that the FDA regulates. However, phase 1 drug and biological products and small studies to determine the feasibility of device products are excluded from the requirement. The NIH policy extends to all NIH-funded trials, including phase 1 clinical trials of FDA-regulated products and small studies to determine the feasibility of products; it also applies to products that the FDA does not regulate, including behavioral interventions.

    Here’s more from Just Care: