BMJ Investigation Increases Concerns About Ticagrelor Trials
An investigation by The BMJ is raising fresh concerns about the clinical studies that supported the approval of the antiplatelet drug ticagrelor (Brilinta, AstraZeneca), almost 15 years after the medication was first approved and as generic versions are set to hit the market.
Peter Doshi, PhD, a senior editor at The BMJ , previously reported inconsistencies and omissions in data reporting from the 2009 PLATO study, published in The New England Journal of Medicine , which showed ticagrelor was superior to clopidogrel in treating acute coronary syndrome.
Now a follow-up investigation of two supporting studies published in Circulation , ONSET/OFFSET and RESPOND, has revealed primary endpoints were reported inaccurately, data were missing from the submission to the US Food and Drug Administration (FDA), and study centers may not have received adequate training.
Doshi said the results of his investigations call into question the drug's approval and suggested that it should be revisited.
'The FDA's approval in 2011 went against the evidence according to its reviewers, and now, my investigations into PLATO, ONSET/OFFSET, and RESPOND, suggest that even the data presented to the FDA and reported in The New England Journal of Medicine and Circulation , is not trustworthy,' he told Medscape Medical News.
The investigation identified several problems with data integrity in the two trials. The original primary endpoint results for RESPOND, which aimed to test whether ticagrelor could convert nonresponders to clopidogrel into responders, were statistically nonsignificant ( P = .157) but were subsequently reported in Circulation as significant ( P = .005) because of an undeclared change in its primary endpoint definition.
For ONSET/OFFSET, which reported ticagrelor provided faster and greater inhibition of platelets than clopidogrel, the investigators now claim several patients were excluded from the analysis. However, those who remained were identified as the 'intention-to-treat' population, implying all patients were included. Implausible data points were also included in the analysis of the primary endpoint but were first transformed through an unpublished data analysis, Doshi claimed.
Doshi also gained access to readouts from some of the platelet function test machines used in the trial. He found more than 60 of 282 readings were not present in the datasets submitted to the FDA, and the levels of platelet activity in those readings were significantly higher than those reported in Circulation .
Victor Serebruany, MD, from Johns Hopkins University in Baltimore, and one of the more high-profile critics of ticagrelor, told The BMJ the missing readings show 'there are episodes of skyrocketing rebound and profound platelet inhibition after ticagrelor, making patients prone to thrombosis or bleeding. If doctors had known what happened in these trials, they would never have started using ticagrelor.'
The investigation also revealed oddities around the authorship of the publications. One active trial investigator was never identified as a study author, while one author told The BMJ he was not involved in the trial.
The BMJ states that AstraZeneca, the journal Circulation , and many of the original investigators either declined to comment on the new claims or were unreachable.
Ticagrelor has been under fire since the beginning. The drug failed in its first bid for FDA approval and was the subject of an investigation by the US Department of Justice in 2013 at the urging of Serebruany. That investigation was closed in 2014 with no further action.
A review of several major trials of ticagrelor by Eric Bates, MD, professor of internal medicine at the University of Michigan in Ann Arbor, Michigan, and a co-author of the US guidelines that recommend ticagrelor, concluded 'the clinical conventional wisdom and clinical trial guideline support for…ticagrelor compared with clopidogrel may be overemphasized.' Bates is now calling for a review of ticagrelor's recommendation in guidelines, according to the earlier The BMJ report.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
CNN
an hour ago
- CNN
I tossed my expensive makeup to get rid of my acne. Here are the noncomedogenic products I use now
Noncomedogenic makeup quick picks Skin tint: Make Beauty Diffusion Dew Radiant Skin Tint Highlighter: Haus Labs by Lady Gaga Bio-Radiant Gel-Powder Illuminating Highlighter Setting powder: RMS Beauty Un Powder Brow gel: Kimiko The Brow Sensei In my mid-twenties, I was hit with a wave of stubborn cystic acne that covered my face seemingly overnight. After trying countless products, the real shift came when I switched to Clearstem — a noncomedogenic (aka non-pore-clogging) skin care line designed to tackle breakouts and wrinkles. While my skin finally started to clear, I still couldn't shake some breakouts — until I realized my makeup products might be the culprit. It turns out even beauty products can clog pores! So, I did something dramatic and expensive: I cross-checked my makeup ingredients using Clearstem's Pore-Clogging Ingredients Checker, tossed everything I owned and started fresh. After lots of trial and error, I finally found the best noncomedogenic makeup, from Charlotte Tilbury to Rare Beauty and more. Merit Great Skin Instant Glow Serum There's a reason this serum has 'glow' in its name. Worn with makeup or by itself, it leaves my skin looking lit from within, thanks to ingredients like hyaluronic acid and niacinamide. Make Beauty Diffusion Dew Radiant Skin Tint This lightweight foundation features skin-mimicking pigments that blur, smooth and brighten. It's sheer yet buildable, making it perfect for a second-skin or full-coverage glam look. Rare Beauty Warm Wishes Effortless Cream Bronzer Stick You may have seen this bronzing stick all over TikTok, and I can confirm it's worth the hype! It glides on effortlessly and melts into my skin for the most natural, sun-kissed glow. Huda Beauty Easy Blur Primer My colleague, associate testing writer Carolina Gazal, also has acne-prone skin and said she's "extremely careful when it comes to [her] makeup choices." She swears by this silicone-free, noncomedogenic primer. "I love this jelly-like, antioxidant-rich formula that blurs pores instantly," she said. "It's also made with glycerin to control oil, making foundation last longer without that dreaded T-zone shine." Haus Labs by Lady Gaga Bio-Radiant Gel-Powder Illuminating Highlighter Leave it to Lady Gaga to create the best highlighter on the market. This pressed-powder formula is packed with glow-boosting ingredients that make my cheekbones truly shine. Priia Lip Butter Balm Summer Fridays, who? This under-$10, buildable vegan lip butter balm is infused with acne-safe botanicals and leaves my lips looking and feeling hydrated and plump. Charlotte Tilbury Airbrush Flawless Setting Spray Good news: Not all Charlotte Tilbury products include pore-clogging ingredients! That includes the brand's ultra-viral setting spray, which locks in makeup all day long. RMS Beauty Un Powder Formulated with silica, this nontoxic setting powder instantly absorbs oil and minimizes the appearance of pores. Best of all, it's never drying, so it's great for all skin types. Kimiko The Brow Sensei Not only does this clear gel style and keep my brows in place but it's made with growth- and hair-enhancing peptides. I swear, my brows have never looked fuller! Olio E Osso Tinted Balm Associate deals editor Elena Matarazzo said she stocks up on these sensitive skin-friendly multisticks for friends and family. They're made with natural oils and waxes but none that are flagged as pore cloggers. "The clear one is great for chapped hands, cheeks and other areas that need a bit of hydration, while the tinted version doubles as a lip balm and blush," she said. Know how pore cloggers work Your first step to putting your best face forward? Staying up to date on what might actually be clogging your pores in the first place. Danielle Gronich, co-founder and CEO of Clearstem, suggests 'thinking of pore cloggers as ingredients that create a sticky, occlusive film on your skin. This film traps dead skin cells, oil and bacteria inside your pores, leading to congestion, blackheads, whiteheads and, ultimately, pimples.' Look for the right products When sourcing the right noncomedogenic products for your skin, it helps to know which ingredients are worth prioritizing. 'We want ingredients that are both skin-loving and noncomedogenic,' Gronich said. 'Look for hyaluronic acid, niacinamide, zinc oxide, green tea extract and kaolin clay.' While sourcing the best noncomedogenic ingredients is a solid place to start, it's only part of the equation. Consider steering clear of what our experts deem pore-clogging ingredients as well. 'Some ingredients that may be considered pore clogging include cocoa butter, isopropyl myristate, coconut oil and ethylhexyl palmitate,' Dr. Marisa Garshick, a board-certified dermatologist at MDCS Dermatology, said. Learn more about your own skin What works for one person's skin might yield a breakout in another, so it helps to track patterns in your own skin or book a consultation with a skin specialist or dermatologist to gain tangible insights into what might fare best for you. 'Just because ingredients may be pore clogging, it doesn't mean everyone who uses them will necessarily experience breakouts,' Garshick said. The following FAQs have been answered by Dr. Marisa Garshick and Clearstem co-founder and CEO Danielle Gronich. What is noncomedogenic makeup? What is noncomedogenic makeup? 'Noncomedogenic makeup is formulated without the heavy, occlusive ingredients that are known to clog pores,' Gronich said. 'It allows your skin to 'breathe' and function properly, helping minimize the risk of breakouts. It's designed to be gentler and more compatible with acne-prone skin.' However, Gronich also said that just because 'noncomedogenic' is on the label, that doesn't guarantee that a product is truly acne-safe. 'The term isn't tightly regulated, so some products may still contain ingredients that can clog pores — especially for those with sensitive or acne-prone skin,' she said. 'Always check the full ingredient list for pore cloggers. What works for one person may trigger breakouts in another, so being your own skin detective is key!' How do I check for pore-clogging ingredients in makeup? How do I check for pore-clogging ingredients in makeup? 'I always tell people to check the ingredient list,' Gronich said. 'We created an online resource, Clearstem's Pore-Clogging Ingredients Checker, where you can input your products and see if they have pore cloggers.' In addition to checking new products you want to try, Garshick said to check for pore-clogging ingredients every time you repurchase a product too. 'Brands can change their formulations for a variety of reasons at any time, so it's always best to double-check,' she said. Besides impacting acne-prone skin, how else do pore-clogging ingredients negatively affect skin? Besides impacting acne-prone skin, how else do pore-clogging ingredients negatively affect skin? 'In some cases, pore-clogging ingredients may lead to milia formation, even in those who are not acne-prone,' Garshick said. 'Some ingredients may also be irritating on the skin, which should be considered for those with sensitive skin.' The dermatologist also said that pore-clogging ingredients may even create a barrier on the skin, which can make other products less effective since they won't penetrate as well. For this article, we consulted the following experts to gain their professional insights. Dr. Marisa Garshick, board-certified dermatologist at MDCS Dermatology in New York and New Jersey Danielle Gronich, co-founder and CEO of Clearstem Here at CNN Underscored, we make it our job to stay up to date on all the latest products, but we don't just find them; we also rigorously test products from hundreds of brands to make sure every product we recommend is worthy of your money. In addition to hands-on testing many of the products we feature, we also consult top experts to understand what qualities, benefits and possible downsides each item offers. We also seek out important considerations and advice from our experts to help give you the information you need to make smarter shopping decisions. For this article, our director of social, Stephanie Griffin, shared her favorite noncomedogenic makeup and tips for finding products that won't clog your pores.
Yahoo
an hour ago
- Yahoo
With 59% institutional ownership, eHealth, Inc. (NASDAQ:EHTH) is a favorite amongst the big guns
Institutions' substantial holdings in eHealth implies that they have significant influence over the company's share price The top 17 shareholders own 51% of the company Insiders have been buying lately AI is about to change healthcare. These 20 stocks are working on everything from early diagnostics to drug discovery. The best part - they are all under $10bn in marketcap - there is still time to get in early. Every investor in eHealth, Inc. (NASDAQ:EHTH) should be aware of the most powerful shareholder groups. The group holding the most number of shares in the company, around 59% to be precise, is institutions. That is, the group stands to benefit the most if the stock rises (or lose the most if there is a downturn). Since institutional have access to huge amounts of capital, their market moves tend to receive a lot of scrutiny by retail or individual investors. Therefore, a good portion of institutional money invested in the company is usually a huge vote of confidence on its future. In the chart below, we zoom in on the different ownership groups of eHealth. Check out our latest analysis for eHealth Institutional investors commonly compare their own returns to the returns of a commonly followed index. So they generally do consider buying larger companies that are included in the relevant benchmark index. We can see that eHealth does have institutional investors; and they hold a good portion of the company's stock. This can indicate that the company has a certain degree of credibility in the investment community. However, it is best to be wary of relying on the supposed validation that comes with institutional investors. They too, get it wrong sometimes. It is not uncommon to see a big share price drop if two large institutional investors try to sell out of a stock at the same time. So it is worth checking the past earnings trajectory of eHealth, (below). Of course, keep in mind that there are other factors to consider, too. Since institutional investors own more than half the issued stock, the board will likely have to pay attention to their preferences. It looks like hedge funds own 14% of eHealth shares. That worth noting, since hedge funds are often quite active investors, who may try to influence management. Many want to see value creation (and a higher share price) in the short term or medium term. Our data shows that 8 Knots Management, LLC is the largest shareholder with 8.1% of shares outstanding. For context, the second largest shareholder holds about 5.6% of the shares outstanding, followed by an ownership of 4.4% by the third-largest shareholder. In addition, we found that Francis Soistman, the CEO has 2.3% of the shares allocated to their name. After doing some more digging, we found that the top 17 have the combined ownership of 51% in the company, suggesting that no single shareholder has significant control over the company. Researching institutional ownership is a good way to gauge and filter a stock's expected performance. The same can be achieved by studying analyst sentiments. There are plenty of analysts covering the stock, so it might be worth seeing what they are forecasting, too. While the precise definition of an insider can be subjective, almost everyone considers board members to be insiders. Management ultimately answers to the board. However, it is not uncommon for managers to be executive board members, especially if they are a founder or the CEO. Insider ownership is positive when it signals leadership are thinking like the true owners of the company. However, high insider ownership can also give immense power to a small group within the company. This can be negative in some circumstances. We can report that insiders do own shares in eHealth, Inc.. As individuals, the insiders collectively own US$7.4m worth of the US$123m company. It is good to see some investment by insiders, but we usually like to see higher insider holdings. It might be worth checking if those insiders have been buying. With a 21% ownership, the general public, mostly comprising of individual investors, have some degree of sway over eHealth. While this size of ownership may not be enough to sway a policy decision in their favour, they can still make a collective impact on company policies. It's always worth thinking about the different groups who own shares in a company. But to understand eHealth better, we need to consider many other factors. Take risks for example - eHealth has 2 warning signs we think you should be aware of. If you are like me, you may want to think about whether this company will grow or shrink. Luckily, you can check this free report showing analyst forecasts for its future. NB: Figures in this article are calculated using data from the last twelve months, which refer to the 12-month period ending on the last date of the month the financial statement is dated. This may not be consistent with full year annual report figures. Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team (at) article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
an hour ago
- Yahoo
Media Alert: House of Good Presents the Well+Good Shop
Self-Care Studio to Help Shoppers Find Their New Self-Care Regimen VENICE, Calif., June 20, 2025 (GLOBE NEWSWIRE) -- Join Well+Good IRL at House of Good to shop feel-good products across home, beauty, fitness, tech, and more all month. WHAT: Escape the hustle of Abbot Kinney and enter into a feel-good emporium—curated with Well+Good editor recommendations. June's Self-Care Studio at the Well+Good Shop is where all forms of self-care converge, blending movement, beauty, and recovery into one immersive, shoppable space. All month long, visit to find the best wellness buys and test & shop your favorite brands, including: Active&Fit Blueair California Walnuts ThirdLove Auratherapy Aviron Canopy Cariuma Hyperice KORRES Lifepro Fitness NordicTrack NOYZ HigherDOSE Homecourt Public Goods Wildling WHO: This event is free and open to the public. WHEN: June 20 - 29, 2025, open Thursdays - Sundays, 12 p.m. - 7 p.m. Visit for aura photography presented by Auratherapy throughout the month. Additional special activations include: Friday, June 20: Greek Yogurt Sampling Bar presented by KORRES Saturday, June 21: Breathwork Session with The Breathing Room Saturday, June 21: Gua Sha Demonstration with Wildling Saturday, June 28: Meditation Session with Grace Whitlock Saturday, June 28 and Sunday, June 29: Trail Mix Sampling Bar presented by California Walnuts. WHERE: House of Good: 1511 Abbot Kinney Blvd, Los Angeles, CA 90291 To learn more, visit About Well+GoodWell+Good is a health and wellness media brand, known for its journalistic integrity, expert-led editorial, and ahead-of-the-curve trend-spotting. Founded in 2010, Well+Good delivers inclusive content that makes the path to feeling good feel good—for everyone. By amplifying different perspectives, experiences, and stories, Well+Good helps people decide on the lifestyle changes that work for them. The female-founded company has been recognized as a vertical media leader and creates high-quality consumer events at House of Good, its real-life home in Venice, CA. About World of Good BrandsWorld of Good Brands is a leader in experiential media and commerce operating premium lifestyle brands including Well+Good, OnlyInYourState, and House of Good. World of Good Brands creates consumer experiences that blend physical and virtual – allowing audiences to access them from wherever they are, and taking a piece of them wherever they go. While traditional media companies broadcast, World of Good Brands narrowcasts: the brands close the aperture on the communities, conversations, and connections that bring color and meaning to our worlds. The World of Good Brands niche digital properties have deep connections with their consumers, and can be amplified through a collection of 50+ digital properties representing consumers across lifestyles and life stages: offering premium reach and powerful audience extension opportunities for partners. Formerly known as Leaf Group Media, World of Good Brands is a Graham Holdings Company (NYSE: GHC) subsidiary. To learn more, visit Media ContactSusan TurnerSenior Director, in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
