Parents’ exposure to chemicals prior to conception linked to child’s health problems

Life-Long Implications of Developmental Exposure to Environmental Stressors

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A couple’s exposure to endocrine-disrupting chemicals, psychological stress, malnutrition, and other environmental stressors prior to conceiving a child may alter the child’s genetic structure and development, leading to increased risk of health issues later in life, according to a study led by Philippe Grandjean, adjunct professor of environmental health at Harvard T.H. Chan School of Public Health and professor of environmental medicine at the University of Southern Denmark.

Parents’ Preconception Exposure to Environmental Stressors Can Disrupt Early Developmental Processes, Endocrine Society, August 04, 2015.

Even before a child is conceived, the parents’ exposure to environmental stressors can alter the way genes are expressed and ultimately harm the child’s health when those genes are passed down to the next generation, according to a new article published in the Endocrine Society’s journal Endocrinology.

Exposure to environmental stressors such as endocrine-disrupting chemicals, psychological stress and malnutrition may result in disadvantageous epigenetic “reprogramming” that can echo through multiple generations.  When these stressors disrupt early developmental processes, they may cause changes in cellular gene expression, cell numbers or locations of cells that persist and lead to increased risk of cognitive disorders, obesity, diabetes and metabolic diseases later in life.

The article summarizes key insights from the 4th Conference on Prenatal Programming and Toxicity (PPTOX IV). More than 300 people attended the event in Boston, MA in October 2014. The meeting featured more than 60 oral and 130 poster presentations discussing the impact of chemical, physical and biological environmental stressors on the interconnected relationships of endocrine, immune and nervous systems.

Previous research on environmental stressors focused primarily on exposures during pregnancy and early childhood and their effects on the health of the offspring across the lifespan. However, presentations at PPTOX IV emphasized that the preconception period in both females and males is also a sensitive developmental window.

In regard to environmental stressors, a good start lasts a lifetime,” said Philippe Grandjean, MD, PhD, Professor of Environmental Medicine at the University of Southern Denmark and Adjunct Professor of Environmental Health at the Harvard T.H.Chan School of Public Health and an author of the article. “Unfortunately, current testing paradigms do not properly assess the impact of risk factors during vulnerable exposure windows. Without new policies and guidelines, we cannot have a universal healthy start for children.”

Researchers note that regulatory agencies currently may not appropriately take into account the potential for non-linear effects of certain environmental chemicals, meaning that exposure to low levels of a chemical can have different adverse effects than what could be experienced at exposure to higher levels of the same chemical.

The conference also highlighted the importance of placental function and the need to understand how changes in placental status may affect fetal development, as well as the importance of mixed stress exposures.

More information
  • Developmental Origins of Health and Disease: Integrating Environmental Influences, endocrine, August 04, 2015.
  • Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives, endocrine, August 04, 2015.
  • List of Endocrine Disrupting Chemicals articles by The Endocrine Society.

 

Leading medical journals editors call for greater data sharing on clinical trials

The ICMJE plans to adopt data-sharing requirements after considering feedback received to the proposals made

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Editors from leading medical journals proposed expansive new data-sharing requirements for authors writing about clinical experiments.

Sharing Clinical Trial Data: A Proposal From the International Committee of Medical Journal Editors, Annals of Internal Medicine, 20 January 2016.

The International Committee of Medical Journal Editors (ICMJE) believes that there is an ethical obligation to responsibly share data generated by interventional clinical trials because participants have put themselves at risk. In a growing consensus, many funders around the world—foundations, government agencies, and industry—now mandate data sharing. Here we outline ICMJE’s proposed requirements to help meet this obligation. We encourage feedback on the proposed requirements. Anyone can provide feedback at icmje.org by 18 April 2016.

The ICMJE defines a clinical trial as any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the cause-and-effect relationship between a health-related intervention and a health outcome. Further details may be found in the Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals at www.icmje.org.

As a condition of consideration for publication of a clinical trial report in our member journals, the ICMJE proposes to require authors to share with others the deidentified individual-patient data (IPD) underlying the results presented in the article (including tables, figures, and appendices or supplementary material) no later than 6 months after publication. The data underlying the results are defined as the IPD required to reproduce the article’s findings, including necessary metadata. This requirement will go into effect for clinical trials that begin to enroll participants beginning 1 year after the ICMJE adopts its data-sharing requirements. (The ICMJE plans to adopt data-sharing requirements after considering feedback received to the proposals made.)

Enabling responsible data sharing is a major endeavor that will affect the fabric of how clinical trials are planned and conducted and how their data are used. By changing the requirements of the manuscripts we will consider for publication in our journals, editors can help foster this endeavor. As editors, our direct influence is logically, and practically, limited to those data underpinning the results and analyses we publish in our journals.

The ICMJE also proposes to require that authors include a plan for data sharing as a component of clinical trial registration. This plan must include where the researchers will house the data and, if not in a public repository, the mechanism by which they will provide others access to the data, as well as other data-sharing plan elements outlined in the 2015 Institute of Medicine Report (e.g., whether data will be freely available to anyone upon request or only after application to and approval by a learned intermediary, whether a data use agreement will be required) (1). ClinicalTrials.gov has added an element to its registration platform to collect data-sharing plans. We encourage other trial registries to similarly incorporate mechanisms for the registration of data-sharing plans. Trialists who want to publish in ICMJE member journals (or nonmember journals that choose to follow these recommendations) should choose a registry that includes a data-sharing plan element as a specified registry item or allows for its entry as a free-text statement in a miscellaneous registry field. As a condition of consideration for publication in our member journals, authors will be required to include a description of the data-sharing plan in the submitted manuscript. Authors may choose to share the deidentified IPD underlying the results presented in the article under less restrictive, but not more restrictive, conditions than were indicated in the registered data-sharing plan.

ICMJE already requires the prospective registration of all clinical trials prior to enrollment of the first participant. This requirement aims, in part, to prevent selective publication and selective reporting of research outcomes, and to prevent unnecessary duplication of research effort. Including a commitment to a data-sharing plan is a logical addition to trial registration that will further each of these goals. Prospective trial registration currently includes documenting the planned primary and major secondary end points to be assessed, which enables identification of incomplete reporting as well as post hoc analyses. Declaring the plan for sharing data prior to their collection will further enhance transparency in the conduct and reporting of clinical trials by exposing when data availability following trial completion differs from prior commitments.

Sharing clinical trial data, including deidentified IPD, requires planning to ensure appropriate ethics committee or institutional review board approval and the informed consent of study participants. Accordingly, we will defer these requirements for 1 year to allow investigators, trial sponsors, and regulatory bodies time to plan for their implementation.

Just as the confidentiality of trial participants must be protected (through the deidentification of IPD), and the needs of those reasonably requesting data met (through the provision of useable data), the reasonable rights of investigators and trial sponsors must also be protected. ICMJE proposes the following to safeguard these rights. First, ICMJE editors will not consider the deposition of data in a registry to constitute prior publication. Second, authors of secondary analyses using these shared data must attest that their use was in accordance with the terms (if any) agreed to upon their receipt. Third, they must reference the source of the data using a unique identifier of a clinical trial’s data set to provide appropriate credit to those who generated it and allow searching for the studies it has supported. Fourth, authors of secondary analyses must explain completely how theirs differ from previous analyses. In addition, those who generate and then share clinical trial data sets deserve substantial credit for their efforts. Those using data collected by others should seek collaboration with those who collected the data. However, because collaboration will not always be possible, practical, or desired, an alternative means of providing appropriate credit needs to be developed and recognized in the academic community. We welcome ideas about how to provide such credit.

Data sharing is a shared responsibility. Editors of individual journals can help foster data sharing by changing the requirements of the manuscripts they will consider for publication in their journals. Funders and sponsors of clinical trials are in a position to support and ensure adherence to IPD sharing obligations. If journal editors become aware that IPD sharing obligations are not being met, they may choose to request additional information; to publish an expression of concern; to notify the sponsors, funders, or institutions; or in certain cases, to retract the publication.

In the rare situation in which compliance with these requirements is impossible, editors may consider authors’ requests for exceptions. If an exception is made, the reason(s) must be explained in the publication.

Sharing data will increase confidence and trust in the conclusions drawn from clinical trials. It will enable the independent confirmation of results, an essential tenet of the scientific process. It will foster the development and testing of new hypotheses. Done well, sharing clinical trial data should also make progress more efficient by making the most of what may be learned from each trial and by avoiding unwarranted repetition. It will help to fulfill our moral obligation to study participants, and we believe it will benefit patients, investigators, sponsors, and society.

Related news: Medical journal editors call for greater data sharing on clinical trials, statnews, 20 January 2016.

Meds money: the sky-high price of many prescription drugs

Why do some med drugs cost so much while others don’t?

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Experts say greed is a big reason for the sky-high price of some prescription pills. But it’s not the only reason says Jamie Reno.

Doctors want lower medicine drug prices, too…

Prescription drug prices in America are through the roof, and they’re still going up.

Consumers spent $374 billion on medicine in 2014, according to the IMS Institute for Healthcare. That’s 13 percent more than the previous year.

Hepatitis C drugs alone accounted for more than $11 billion in new spending last year. Perhaps that is no surprise, as the drugs Sovaldi and Harvoni both cost more than $1,000 per pill.

Scientific American reports that the average price of a new cancer drug now exceeds $100,000 a year. Even a cancer patient with insurance could spend $25,000 out of pocket.

And then there are people like Turing Pharmaceuticals’ Chief Executive Officer Martin Shkreli — aka “Pharma Bro” — whose apparent greed in raising the price of a lifesaving drug by 5,000 percent has infuriated the public. Shkreli was arrested Thursday morning on security fraud charges stemming from when he was a hedge fund manager and overseeing the biopharmaceutical company Retrophin.

Even generics are getting pricey…

With all of this going on, you may ask: Why are drug prices so high?

The answer isn’t as simple as you might think. Is corporate greed a factor? Yes, but experts say it’s a bit more complicated than that “…

… continue reading Why some drugs cost so huch and others don’t, on healthline, by Jamie Reno, 17 December 2015.

RANBP1 Gene may link to Autism and other Neuro Disorders

The finding could open new research opportunities for treatment for multiple neurological diseases

image of autism disorders
Autism is the best known a large group of heritable neuropsychiatric conditions associated with identifiable genetic disorders in which patients have impaired social interaction and communication.

Newly Identified RANBP1 Gene may be important in autism disorders, other neuropsychiatric syndromes

Scientists have identified a gene that appears to play a significant role in raising a person’s risk of having more severe subtypes of autism that co-occur with other genetic diseases, such as the chromosomal disorder 22q11.2 deletion syndrome. Variations in this gene, RANBP1, may disrupt brain signaling in different neuropsychiatric conditions—a finding that could open new research opportunities for treatment for multiple neurological diseases.

Abstract

While abnormal signaling mediated through metabotropic glutamate receptor 5 (mGluR5) is involved in the pathophysiology of Autism Spectrum Disorder (ASD), Fragile X Syndrome and Tuberous Sclerosis, the role of other mGluRs and their associated signaling network genes in syndromic ASD is unknown. This study sought to determine whether mGluR Copy Number Variants (CNV’s) were overrepresented in children with syndromic ASD and if mGluR “second hit” confers additional risk for ASD in 22q11.2 Deletion Syndrome (22q11DS). To determine whether mGluR network CNV’S are enriched in syndromic ASD, we examined microarrays from children with ASD (n = 539). Patient categorization (syndromic vs nonsyndromic) was done via blinded medical chart review in mGluR positive and randomly selected mGluR negative cases. 11.5% of ASD had mGluR CNV’s vs. 3.2% in controls (p < 0.001). Syndromic ASD was more prevalent in children with mGluR CNVs (74% vs 16%, p < 0.001). A comparison cohort with 22q11DS (n = 25 with ASD, n = 50 without ASD), all haploinsufficient for mGluR network gene RANBP1, were evaluated for “second mGluR hits”. 20% with 22q11.2DS + ASD had “second hits” in mGluR network genes vs 2% in 22q11.2DS-ASD (p < 0.014). We propose that altered RANBP1 expression may provide a mechanistic link for several seemingly unrelated genetic and environmental forms of ASD.

Sources and more information

  • The Role of mGluR Copy Number Variation in Genetic and Environmental Forms of Syndromic Autism Spectrum Disorder, nature, 19 January 2016.
  • Gene may be important in autism disorders, other neuropsychiatric syndromes, medicalxpress, 19 January 2016.
  • Newly Identified Gene May Link to Autism and Other Neuro Disorders, genengnews, 20 January 2016.
  • RANBP1 gene may increase risk for severe ASD subtypes, healio, January 22, 2016.

Can clinical trials funding source be associated with favorable published outcomes?

Outcome Reporting Among Drug Trials Registered in ClinicalTrials.gov

image of casino-roulette
Medical science is being undermined when researchers do not publish all their findings, or are changing the things they are measuring after looking at the data… Matt Buck.

Abstract

Through increased awareness of misreported outcomes, individual accountability, and feedback for specific journals, could we improve the quantity and quality of the medical data released to the general public?

Background
Clinical trial registries are in widespread use to promote transparency around trials and their results.

Objective
To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes.

Design
An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006.

Setting
ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999.

Measurements
Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations.

Results
Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization–funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization–funded trials without industry contributions (P = 0.005 across groups).

Limitations
The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting.

Conclusion
In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources.

Sources and more information
  • Outcome Reporting Among Drug Trials Registered in ClinicalTrials.gov, NCBI PMCID: PMC3374868, 2012 Jun 14.
  • How Scientists Are Doing A Bait-And-Switch With Medical Data, BuzzFeed, Jan. 22, 2016.
  • The COMPare (CEBM Outcome Monitoring Project) website and blog.

Specific genetic pattern in womb might predict whether or not IVF treatment is likely to be successful

Fertility experts identify genetic pattern in womb linked to IVF failure

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Fertility experts in Southampton and the Netherlands have identified a specific genetic pattern in the womb that could predict whether or not IVF treatment is likely to be successful.

Abstract

The discovery should help clinicians understand why IVF fails repeatedly in some women.

The primary limiting factor for effective IVF treatment is successful embryo implantation. Recurrent implantation failure (RIF) is a condition whereby couples fail to achieve pregnancy despite consecutive embryo transfers. Here we describe the collection of gene expression profiles from mid-luteal phase endometrial biopsies (n = 115) from women experiencing RIF and healthy controls. Using a signature discovery set (n = 81) we identify a signature containing 303 genes predictive of RIF. Independent validation in 34 samples shows that the gene signature predicts RIF with 100% positive predictive value (PPV). The strength of the RIF associated expression signature also stratifies RIF patients into distinct groups with different subsequent implantation success rates. Exploration of the expression changes suggests that RIF is primarily associated with reduced cellular proliferation. The gene signature will be of value in counselling and guiding further treatment of women who fail to conceive upon IVF and suggests new avenues for developing intervention.

Sources and more information
  • An endometrial gene expression signature accurately predicts recurrent implantation failure after IVF, nature, 22 January 2016.
  • Fertility experts identify genetic pattern in womb linked to IVF failure, University of Southampton, 22 January 2016.

Pharmaceutical, Biotechnology and Diagnostics Industries Declaration on Combating Antimicrobial Resistance

More than 80 pharmaceutical companies have called on governments to develop new ways of paying them to develop antibiotics

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On January 21, 2016, the Declaration by the Pharmaceutical, Biotechnology and Diagnostics Industries on Combating Antimicrobial Resistance was launched at an event at the World Economic Forum in Davos, Switzerland.

More than 80 leading international pharmaceutical, generics, diagnostics and biotechnology companies, as well as key industry bodies, have come together to call on governments and industry to work in parallel in taking comprehensive action against drug-resistant infections – socalled ‘superbugs’ – with a joint declaration launched today at the World Economic Forum in Davos, Switzerland. The statement sets out for the first time how governments and industry need to work together to support sustained investment in the new products needed to beat the challenges of rising drug resistance.

The Declaration by the Pharmaceutical, Biotechnology and Diagnostics Industries on Combating Antimicrobial Resistance – drafted and signed by 85 companies and nine industry associations across 18 countries – represents a major milestone in the global response to these challenges, with commercial drug and diagnostic developers for the first time agreeing on a common set of principles for global action to support antibiotic conservation and the development of new drugs, diagnostics, and vaccines. The industry is calling on governments around the world to now go beyond existing statements of intent and take concrete action, in collaboration with companies, to support investment in the development of antibiotics, diagnostics, vaccines, and other products vital for the prevention and treatment of drug-resistant infections.

In particular, the Declaration supports a continuation of efforts towards improved conservation of antibiotics, including a call for improved uptake of rapid point-of-care diagnostics to improve how antibiotics are prescribed, and changes to incentive structures within health systems that directly reward doctors, pharmacists and veterinarians for prescribing antibiotics in greater volumes.

In what the Review on Antimicrobial Resistance recognises to be a notable step for the industry, the signatory companies call on governments to work with them to develop new and alternative market structures that provide more dependable and sustainable market models for antibiotics, and to commit the funds needed to implement them. These mechanisms are needed to provide appropriate incentives (coupled with safeguards to support antibiotic conservation) for companies to invest in R&D to overcome the formidable technical and scientific challenges of antibiotic discovery and development. These include mechanisms to ensure that, where appropriate, the pricing of antibiotics more adequately reflects the benefits they bring; and novel payment models that reduce the link between the profitability of an antibiotic and the volume sold. An integral part of these models is a reduced need for promotional activity by companies.

As well as calling for continued progress by governments on these fronts, the Declaration sets out a commitment to further action on drug resistance by its signatories, which the Review warmly welcomes. These span across three broad areas:

  • Reducing the development of drug resistance
    The companies commit to encouraging better and more appropriate use of new and existing antibiotics, including through work that supports the antibiotic stewardship principles set out by the World Health Organization (WHO) Global Action Plan on antimicrobial resistance (AMR), and via improved education of clinicians. This support extends to promoting more judicious use of antibiotics in livestock, as part of a ‘one health’ approach.
  • Increasing investment in R&D that meets global public health needs
    Recognising the need to increase research into new antibiotics, diagnostics, vaccines and other alternative treatments, the companies commit to a continuation and extension of collaborative initiatives between industry, academia and public bodies to improve how R&D in the field is done and provide greater opportunities for the scientific barriers to antibiotic discovery to be overcome.
  • Improve access to high-quality antibiotics for all
    In light of the gaps that remain in global access to our existing antibiotics and vaccines, and the importance of ensuring that new generations of products are available to all those who need them, the signatories commit to supporting initiatives aimed at ensuring affordable access to antibiotics in all parts of the world, at all levels of income.

By bringing together such a wide range of companies in this unprecedented way, the Declaration provides a valuable roadmap to guide further collaborative efforts between industry, governments and NGOs in the global fightback against AMR. The Review will continue to work to drive progress towards a series of key international milestones in 2016 – including likely discussions on AMR at the UN General Assembly and as part of China’s G20 programme in the autumn – and in support of progress against the WHO Global Action Plan on AMR.

The Declaration will be updated every two years, to take account of the evolving global landscape of AMR and changing challenges and priorities. It remains open to accept new signatory companies and bodies at any time, with a complete list maintained on the Review on AMR’s website.

Read press notice and quotes

Can clinical trials be designed for marketing purpose?

Are clinical drug trials more marketing than science?

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A new research found that 1 in 5 trials were more likely to be designed for marketing purposes when compared to those that were not.

Abstract

What factors influence the design of a clinical trial?

Background
Analysis of trial documentation has revealed that some industry-funded trials may be done more for marketing purposes than scientific endeavour. We aimed to define characteristics of drug trials that appear to be influenced by marketing considerations and estimate their prevalence.

Methods
We examined reports of randomised controlled trials of drugs published in six general medical journals in 2011. Six investigators independently reviewed all publications, characterising them as YES/MAYBE/NO suspected marketing trials, and then met to reach consensus. Blinded researchers then extracted key trial characteristics. We used blinded cluster analysis to determine if key variables could characterise the categories of trials (YES/MAYBE/NO).

Clinicians who are involved in a company-sponsored clinical trial significantly increase their prescribing preferences for the sponsor’s drug, irrespective of international guidelines…

Results
41/194 (21 %) trials were categorised as YES, 14 (7 %) as MAYBE, 139 (72 %) as NO. All YES and MAYBE trials were funded by the manufacturer, compared with 37 % of NO trials (p < 0.001). A higher proportion of YES trials had authors or contributors from the manufacturer involved in study design (83 % vs. 19 %), data analysis (85 % vs.15 %) and reporting (81 % vs. 15 %) than NO trials (p < 0.001). There was no significant difference between groups in the median number of participants screened (p = 0.49), but the median number of centres recruiting participants was higher for YES compared with NO trials (171 vs. 13, p < 0.001). YES trials were not more likely to use a surrogate (42 % vs. 30 %; p = 0.38) or composite primary outcome measure (34 % vs. 19 %; p = 0.14) than NO trials. YES trials were often better reported in terms of blinding, safety outcomes and adverse events than NO trials. YES trials more frequently included speculation that might encourage clinicians to use the intervention outside of the study population compared to NO trials (59 % vs.37 %, p = 0.03). Cluster analysis based on study characteristics did not identify a clear variable structure that accurately characterised YES/MAYBE/NO trials.

Conclusions
We reached consensus that a fifth of drug trials published in the highest impact general medical journals in 2011 had features that were suggestive of being designed for marketing purposes. Each of the marketing trials appeared to have a unique combination of features reported in the journal publications.

Sources, full study, more information

  • Characterisation of trials where marketing purposes have been influential in study design: a descriptive study, trials journal, doi:10.1186/s13063-015-1107-1, 21 January 2016.
  • Are clinical drug trials more marketing than science?, biomed central blog, 21 Jan 2016.

World Cancer Day 2016 Key Messages

What can YOU do – as an individual – to help prevent and fight cancer?

Just as cancer affects everyone in different ways, all people have the power to take various actions to reduce the impact that cancer has on individuals, families and communities.

World Cancer Day is a chance to reflect on what you can do, make a pledge and take action. Whatever you choose to do ‘We can. I can.’ make a difference to the fight against cancer.

More information

USA: some insurers pay women to get frequent mammograms

Instead, employers and health plans should offer incentives that reward the use of evidence-based decision aids

image of Woman-and-Mammogram
How widespread is the practice of incentivizing mammograms? Image Jon Krause.
  • A 53-year-old woman on Medicaid in Washington State who has never had a mammogram elects to get one in return for a $15 gift card.
  • A 35-year-old woman in Florida chooses to get her first mammogram because her insurer, Aetna, offers a $50 payroll check.
  • In Iowa, a 46-year-old woman who has been getting mammograms every other year opts to get them annually because Wellmark Blue Cross Blue Shield will pay her $50 to do so.

All three of these women have average risk profiles, and none have family members with breast cancer. Who made the right choice?

It’s a trick question. The real question is whether employers and health plans should really be offering incentives to women to get frequent mammograms.

… continue reading:  Insurer Rewards Push Women Toward MammogramsNY Times, JAN. 18, 2016.