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A pill to fight alcoholism causes an uproar in France

Among the issues they cited was the ANSM decision to approve baclofen before the second study was publicly available. Even before publication, the academics noted the trial sponsor — the Public Assistance Hospital in Paris — touted results in a press release. The hospital also sold study data to Ethypharm, a small company that sought regulatory approval to market the drug, although this was not disclosed in the paper. Curiously, Ethypharm also performed the analysis that was the basis for the ANSM decision. When the Bacloville study was finally published last December, the group of researchers discovered an unexplained change in the primary outcome, a practice that is frowned upon because it can suggest an attempt to achieve desired results. The researchers contend the change in outcomes made it harder to analyze what, if any, difference baclofen had on patients, leading to a bias in favor of the drug. “Biased trials lead to biased decisions, and biased decisions mean that people get treatment that doesn’t work, possibly don’t get treatment that does work, can be harmed by treatment and it costs the health care system more,” said Joel Lexchin, a professor of family and community medicine at the University of Toronto, and one of the researchers who have criticized the Bacloville study.

A brief history of medical statistics and its impact on reproducibility.

By failing to address the structurally driven deficits in scientific and statistical thinking already apparent decades earlier, and then amplifying them with professional incentives to produce more and more research (grossly mismeasured by papers published), medical research had become a scandal. Altman concluded that “We need less research, better research, and research done for the right reasons.” This is, in my opinion, the most important sentence ever written about medical research, but it fell on deaf ears. How do I know this? A decade or so later, the Lancet published a special issue on research waste, which made the case that medical research costing billions of dollars each year is wasted due to things like poor research questions, flawed study designs, erroneous statistical analyses, and clumsy research reports (15).

Senators Who Led Pharma-Friendly Patent Reform Also Prime Targets For Pharma Cash | Kaiser Health News

[…] Early last year, as lawmakers vowed to curb rising drug prices, Sen. Thom Tillis was named chairman of the Senate Judiciary Committee’s subcommittee on intellectual property rights, a committee that had not met since 2007. Explore […] As the new gatekeeper for laws and oversight of the nation’s patent system, the North Carolina Republican signaled he was determined to make it easier for American businesses to benefit from it — a welcome message to the drugmakers who already leverage patents to block competitors and keep prices high. Less than three weeks after introducing a bill that would make it harder for generic drugmakers to compete with patent-holding drugmakers, Tillis opened the subcommittee’s first meeting on Feb. 26, 2019, with his own vow. “From the United States Patent and Trademark Office to the State Department’s Office of Intellectual Property Enforcement, no department or bureau is too big or too small for this subcommittee to take interest,” he said. “And we will.” In the months that followed, tens of thousands of dollars flowed from pharmaceutical companies toward his campaign, as well as to the campaigns of other subcommittee members […]Tillis received more than $156,000 from political action committees tied to drug manufacturers in 2019, more than any other member of Congress, a new analysis of KHN’s Pharma Cash to Congress database shows.[…]

Are FDA Panel Votes on Psych Drugs Tainted by Speakers' COIs?

Members of the public who receive travel and other expenses from pharmaceutical study sponsors to attend US Food and Drug Administration (FDA) advisory panel meetings and provide testimony about the efficacy of a new psychiatric drug are highly likely to deliver a positive opinion, new research shows. Such individuals, investigators say, have the potential to skew outcomes of FDA advisory panel votes, potentially leading to psychiatric drug approvals that are not exclusively based on objective scientific evidence. "The implications of these findings are concerning since COIs have the potential to skew public speakers' testimonies at these meetings and persuade committee members to look beyond the evidence and approve a drug through the acquisition of non–evidence-based information," study investigator William Roberts, a medical student at Oklahoma State University (OSU) College of Osteopathic Medicine in Tulsa, told Medscape Medical News.

Four Reasons Drugs Are Expensive, Of Which Two Are False

Thus there is a lot of deliberate obfuscation of the real prices, net of rebates, discounts, clawbacks, budget caps, etc., that health systems actually pay. Elastic also loosens when there are barriers to trade. The European Union is a free trade zone. Therefore, if one sells pills into Greece, where prices are low, it is more profitable overall to make sure they are in Greek language-only packaging, in Greek language-only blister packs, with something obvious and Greek printed on the pills, and – if possible – in a dose that is subtly different from any dose that can be legally sold in the UK or Germany. This makes it tedious to repackage the pills, before shipping them to parts of the European Union where they compete with similar pills that the manufacturer is selling a higher price: Tedious but not impossible, as German friends taking re-exported Greek drugs recently told me.

Four Reasons Drugs Are Expensive, Of Which Two Are False

From the company’s perspective, the drug was much too cheap. Had Sanofi applied the cancer price to the multiple sclerosis dose, it would have been charging around $6,000 per year when multiple sclerosis drugs had annual prices closer to $60,000. So Sanofi withdrew Campath from commercial sale in late 2012 and re-launched it in 2013 in Europe and in 2014 in the US with a new name, Lemtrada, a new multiple sclerosis indication, and a list price rise of over one thousand – yes, one thousand – percent. The temporary withdrawal outraged neurologists who had been using Campath off-label for years, but who could not get the drug for their patients until the re-launch.

Coca-Cola Funds Scientists Who Shift Blame for Obesity Away From Bad Diets - The New York Times

“Coca-Cola’s sales are slipping, and there’s this huge political and public backlash against soda, with every major city trying to do something to curb consumption,” said Michele Simon, a public health lawyer. “This is a direct response to the ways that the company is losing. They’re desperate to stop the bleeding.” Coke has made a substantial investment in the new nonprofit. In response to requests based on state open-records laws, two universities that employ leaders of the Global Energy Balance Network disclosed that Coke had donated $1.5 million last year to start the organization.

Pharmaceutical industry sponsorship and research outcome and quality: systematic review. - PubMed - NCBI

30 studies were included. Research funded by drug companies was less likely to be published than research funded by other sources. Studies sponsored by pharmaceutical companies were more likely to have outcomes favouring the sponsor than were studies with other sponsors (odds ratio 4.05; 95% confidence interval 2.98 to 5.51; 18 comparisons). None of the 13 studies that analysed methods reported that studies funded by industry was of poorer quality.

Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins | The BMJ

The medical community strives to make decisions based on evidence, but as this case illustrates we have unfortunately arrived at a point where taking the conclusions of clinical trials at face value is apparently a sign of naivette. Conflicts of interest may play an important role in the reporting of scientific findings. The problem is not limited to just a couple of isolated cases but involves the entire culture of medicine that has developed over the past ten years. Put bluntly, the scientific machinery is broken. There is no easy fix, but surely patients deserve better.

Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins | The BMJ

However, disclosure of the relationship would not have changed the troubling end result: A researcher with a history of being funded by SSRI makers completes a 'gold-standard' federally-funded study of post stroke SSRI use, which is published in one of the most prestigious medical journals in the world, and is given a forum in the national media to tell the general public that anyone who has had a stroke, whether or not they have been diagnosed with depression, should start a prophylactic regimen of Lexapro ...even though non-medical approaches perform just as well.

No evidence of added benefit for most new drugs entering German healthcare system: International drug development processes and policies are responsible and must be reformed -- ScienceDaily

And for 125 drugs (58%), the available evidence did not prove an added benefit over standard care in the approved patient population. The situation is particularly shocking in some specialties, they add. For example, in psychiatry/neurology and diabetes, added benefit was shown in just 6% (1/18) and 17% (4/24) of assessments, respectively.

The Pharmaceutical Industry’s Role in U.S. Medical Education » in-Training, the online peer-reviewed publication for medical students

Multiple studies report a relationship between exposure to the pharmaceutical industry and positive attitudes about industry interactions. As students’ exposure to the pharmaceutical industry increases, their ability to determine industry bias decreases. In losing their ability to detect bias and analyze pharmaceutical marketing statements objectively, medical students hinder their future ability to practice evidence-based medicine.

(So does running) Ketamine reverses neural changes underlying depression-related behaviors in mice: Study sheds light on the neural mechanisms underlying remission of depression -- ScienceDaily

Researchers took high-resolution images of dendritic spines in the prefrontal cortex of mice before and after they experienced a stressor. Dendritic spines are protrusions in the part of neurons that receive communication input from other neurons. The researchers found that mice displaying behaviors related to depression had increased elimination of, and decreased formation of, dendritic spines in their prefrontal cortex compared with mice not exposed to a stressor. This finding replicates prior studies linking the emergence of behaviors related to depression in mice with dendritic spine loss. In addition to the effects on dendritic spines, stress reduced the functional connectivity and simultaneous activity of neurons in the prefrontal cortex of mice. This reduction in connectivity and activity was associated with behaviors related to depression in response to stressors. Liston's group then found that ketamine treatment rapidly restored functional connectivity and ensemble activity of neurons and eliminated behaviors related to depression

Inactive ingredients in pills and capsules may cause allergic, adverse reactions: Majority of oral medications available to consumers contain ingredients that can affect sensitive individuals -- ScienceDaily

A new study led by a team of investigators from Brigham and Women's Hospital and Massachusetts Institute of Technology has found that the vast majority of the most frequently prescribed medications in the U.S. contain at least one ingredient capable of causing an adverse reaction. Known as inactive ingredients, these components are added to improve the taste, shelf-life, absorption and other characteristics of a pill, but the authors found that more than 90 percent of all oral medications tested contained at least one ingredient that can cause allergic or gastrointestinal symptoms in sensitive individuals. Such ingredients include lactose, peanut oil, gluten and chemical dyes.

Drug Companies and Doctors Battle Over the Future of Fecal Transplants - The New York Times

Mark Smith, a microbiologist at M.I.T., was halfway through his pitch with a group of pharmaceutical executives when one of them interrupted to ask if the meeting was a prank. “I can’t believe you wasted my time with this crazy idea,” the man said, Dr. Smith later recalled. That was 2012. Later that year he helped found OpenBiome, the nonprofit stool bank that now supplies most of the fecal matter for transplants in the United States. Three years ago, he started his own drug company, Finch Therapeutics, which has raised $77 million. Over the past decade, tens of thousands of Americans with C. diff have been cured through fecal transplants, often with a single dose that can bring patients back from the brink of death. The treatment has more than an 80 percent success rate, according to several studies, and many patients feel better within hours of receiving the procedure, which is usually administered through colonoscopy or capsules containing desiccated fecal matter. The F.D.A. has not formally approved the therapy but it has suspended enforcement of its rules for patients who have failed on antibiotics while it figures out the best way to regulate a regimen that, until recently, was sometimes performed at home by desperate patients using an enema, saline and a relative’s stool. Ms. Duff, the head of the C. diff patients group, credits her own recovery from the disease to a homemade concoction her husband created with his own stool in the kitchen blender.

Side-effects not fully reported in more than 30 percent of healthcare reviews -- ScienceDaily

The new study looked at the reporting of adverse events in 187 systematic reviews published between 2017 and 2018. Systematic reviews in health research aim to summarise the results of controlled healthcare interventions and provide evidence of the effectiveness of a healthcare intervention. Research showed that 35 per cent of reviewers did not fully report the side-effects of the medical intervention under review. Dr Su Golder, from the University of York's Department of Health Sciences, said: "Despite reviewers stating in their own protocols that adverse events should be included in the review, 65 per cent fully reported the event as intended by the protocol, eight per cent entirely excluded them, and the remaining 27 per cent either partially reported or changed the adverse event outcomes." "Just over 60 per cent, however, didn't even include adverse events in their protocols, which suggests that a more proactive approach is needed to prompt reviewers to report on potential harmful side-effects in their reporting of healthcare interventions."

The cumulative effect of reporting and citation biases on the apparent efficacy of treatments: the case of depression

Figure 1 demonstrates the cumulative impact of reporting and citation biases. Of 105 antidepressant trials, 53 (50%) trials were considered positive by the FDA and 52 (50%) were considered negative or questionable (Fig. 1a). While all but one of the positive trials (98%) were published, only 25 (48%) of the negative trials were published. Hence, 77 trials were published, of which 25 (32%) were negative (Fig. 1b). Ten negative trials, however, became ‘positive’ in the published literature, by omitting unfavorable outcomes or switching the status of the primary and secondary outcomes (Fig. 1c). Without access to the FDA reviews, it would not have been possible to conclude that these trials, when analyzed according to protocol, were not positive. Among the remaining 15 (19%) negative trials, five were published with spin in the abstract (i.e. concluding that the treatment was effective). For instance, one article reported non-significant results for the primary outcome (p = 0.10), yet concluded that the trial ‘demonstrates an antidepressant effect for fluoxetine that is significantly more marked than the effect produced by placebo’ (Rickels et al., 1986). Five additional articles contained mild spin (e.g. suggesting the treatment is at least numerically better than placebo). One article lacked an abstract, but the discussion section concluded that there was a ‘trend for efficacy’. Hence, only four (5%) of 77 published trials unambiguously reported that the treatment was not more effective than placebo in that particular trial (Fig. 1d). Compounding the problem, positive trials were cited three times as frequently as negative trials (92 v. 32 citations in Web of Science, January 2016, p < 0.001, see online Supplementary material for further details) (Fig. 1e). Among negative trials, those with (mild) spin in the abstract received an average of 36 citations, while those with a clearly negative abstract received 25 citations. While this might suggest a synergistic effect between spin and citation biases, where negatively presented negative studies receive especially few citations (de Vries et al., 2016), this difference was not statistically significant (p = 0.50), likely due to the small sample size. Altogether, these results show that the effects of different biases accumulate to hide non-significant results from view.

What you don't look for can't hurt your share price...

Only nine of 185 randomized clinical trials and 23 of 259 non-randomized studies and patient reports of methylphenidate in children and adolescents with ADHD reported assessment of psychotic symptoms.

Painting a Nuanced Picture of Brain System Regulation Moods and Movements - Neuroscience News

What’s more, the group found that the serotonin neurons themselves were more complex than originally thought. Rather than just transmitting messages with serotonin, the cortical-projecting neurons also released a chemical messenger called glutamate – making them one of the few known examples of neurons in the brain that release two different chemicals. “It raises the question of whether we should even be calling these serotonin neurons because neurons are named after the neurotransmitters they release,” Ren said. Taken together, these findings indicate that the brain’s serotonin system is not made up of a homogenous population of neurons but rather many subpopulations acting in concert. Luo’s team has identified two groups, but there could be many others. In fact, Robert Malenka, a professor and associate chair of psychiatry and behavioral sciences at Stanford’s School of Medicine, and his team recently discovered a group of serotonin neurons in the dorsal raphe that project to the nucleus accumbens, the part of the brain that promotes social behaviors.

Painting a Nuanced Picture of Brain System Regulation Moods and Movements - Neuroscience News

In a series of behavioral tests, the scientists also showed that serotonin neurons from the two groups can respond differently to stimuli. For example, neurons in both groups fired in response to mice receiving rewards like sips of sugar water but they showed opposite responses to punishments like mild foot shocks. “We now understand why some scientists thought serotonin neurons are activated by punishment, while others thought it was inhibited by punishment. Both are correct – it just depends on which subtype you’re looking at,” Luo said.

Antidepressants don't work, or depression doesn't exist (as a meaningful category)

The real truth isn't found within the published paper but rather within a busy table on page 142 of the online appendix. It is here where the authors report what we want: the actual difference between drugs and placebo, before and after treatment, on the depression rating scales. Here we see that the Cohen's d standardized mean difference effect sizes range from a low of 0.19 to a high of 0.62 with amitriptyline. Thus, amitriptyline exceeds the clinically meaningful threshold of 0.50, with a traditional meta-analytic method. No other drug does so, with the closest second place being fluvoxamine, with a Cohen's d value of 0.44. Looking at all of the agents, 10 drugs have Cohen's d values less than 0.30, which is very small and clinically meaningless, whereas four have effect sizes from 0.30 to 0.34. Thus, 74% (14/19) of antidepressants clearly have little or no clinically important benefit in this analysis (for some reason, no data are provided in this table with two of the drugs). Four drugs have effect sizes of 0.37-0.44, and as noted, one agent exceeds the 0.50 threshold (amitriptyline). Perhaps a clearer conclusion than anything else is the well-proven fact that the tricyclic antidepressants are more effective than newer agents (there were no monoamine oxidase inhibitors in this meta-analysis).

Nonprescription use of Ritalin linked to adverse side effects, UB study finds - University at Buffalo

“We saw changes in the brain chemistry in ways that are known to have an impact on the reward pathway, locomotor activity, and other behaviors, as well as effects on body weight,” Thanos says. “These changes in brain chemistry were associated with serious concerns such as risk-taking behaviors, disruptions in the sleep/wake cycle and problematic weight loss, as well as resulting in increased activity and anti-anxiety and antidepressive effects.” Further research indicated that female subjects were more sensitive to the behavioral effects of methylphenidate than the males. Thanos hopes that studying the effects of methylphenidate on those without ADHD may lead to a greater understanding of how the drug works on the brain and behavior, and can help researchers understand the impact of the drug on young people throughout development. “Understanding more about the effects of methylphenidate is also important as people with ADHD show greater risk to be diagnosed with a drug dependency problem,” Thanos says. “In addition, this study highlights the potential long-range risks college students take in using Ritalin for a quick study boost.”

Cash interests taint drug advice | Nature

Only one author declared a conflict of interest, but further checks by the CSPI revealed that four other authors had failed to disclose research funding from relevant drug companies. The problem could be even worse in guidelines that don't contain conflict-of-interest declarations, warns Merrill Goozner, director of the CSPI's Integrity in Science project. “It is usually the journals and supplements that rely heavily on industry advertising that are least likely to have good disclosure policies.”

Drug Companies & Doctors: A Story of Corruption | by Marcia Angell | The New York Review of Books

It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of TheNew England Journal of Medicine.

The Selling of Attention Deficit Disorder - The New York Times

In an interview last month, Dr. Dodson said he makes a new diagnosis in about 300 patients a year and, because he disagrees with studies showing that many A.D.H.D. children are not impaired as adults, always recommends their taking stimulants for the rest of their lives. He said that concern about abuse and side effects is “incredibly overblown,” and that his longtime work for drug companies does not influence his opinions. He said he received about $2,000 for the 2002 talk for Shire. He earned $45,500 in speaking fees from pharmaceutical companies in 2010 to 2011, according to ProPublica, which tracks such payments. “If people want help, my job is to make sure they get it,” Dr. Dodson said. Regarding people concerned about prescribing physicians being paid by drug companies, he added: “They like a good conspiracy theory. I don’t let it slow me down.”

Pharma’s broken business model — Part 2: Scraping the barrel in drug discovery – Endpoints News

Ac­cord­ing to the Human Pro­tein Atlas, there are 19,613 pro­teins en­coded by the human genome.  Of these, 14,545 (74%) have no known link or re­la­tion­ship with dis­ease, which rules them out as po­ten­tial new drug tar­gets be­cause they fail to meet cri­te­rion 1 above.  Per­haps these pro­teins are non-es­sen­tial, as any de­fi­cien­cies can be com­pen­sated by other pro­teins or path­ways; or per­haps they are es­sen­tial, how­ever any de­fi­cien­cies are lethal be­fore birth so they never have the chance to cause any dis­ease.  In any case, we have no rea­son to be­lieve that tar­get­ing these pro­teins will do any­thing for any known human dis­ease. Now of the 5,068 pro­teins that have any link to dis­ease, 3,131 (16% of all human pro­teins) are con­sid­ered to be “un­drug­gable”, ei­ther be­cause they have no ob­vi­ous pocket ca­pa­ble of bind­ing small mol­e­cule drugs, or be­cause they are in­tra­cel­lu­lar and thus in­ac­ces­si­ble to large pro­teins that can­not pen­e­trate the cell mem­brane.  We must rule out these pro­teins as po­ten­tial new drug tar­gets be­cause we cur­rently have no way to tar­get them, so they fail to meet cri­te­rion 2 above.