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Is Novelty Killing Research Science?

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By: Aaron Rising, PhD

20180419_Essay

source: Sean MacEntee via flickr

Within the past decade or so, researchers have become aware of the prevalence of scientific studies whose results cannot be replicated, which has been dubbed the ‘reproducibility crisis.’ While the phrase may be a slight hyperbole, there is a real concern about how many published scientific studies are valid and reproducible. One of the most eye-opening studies into this issue was in the field of psychology in 2015 where 100 different experimental and correlation studies were redone in order to reproduce the conclusions of the original experiments. Overall, this study found that only 36% of the replicate experiments had significant results, despite 97% of the original set reporting significant results. Combining the two sets of studies (the original and the replicate experiments) resulted in nearly 70% significance of the two experimental sets, essentially meaning that ~25% of the original results were potentially a false positive. While the specific reproducibility percentages are debated (1, 2)  and being talked about in the media (3,4), it is worrying that a sizeable amount of published research, through no fault of the original researchers involved in the study, may turn out to be inaccurate. In a poll by Nature, 70% of researchers reported that they have failed to replicate another groups work. What’s even more troubling? More than half could not replicate their own findings.

There are multiple reasons why reproducibility of a single study can be called into question. Different labs use different mouse strains or cell lines, reagents from different companies or lot numbers can vary, or even two people can inherently perform the same experiment differently. All of these are examples could result in the exact same study ending up on either side of the significance threshold (usually set at p<0.05). And it shouldn’t be ignored that there are laboratories who use more nefarious methods to get positive results such as p-hacking, excessive removal of outliers, or just plain making up or editing data. But a more fundamental issue maybe driving this ‘crisis’, and it is one of ‘novelty.’  As humans, we love novelty. We are attracted to things that are innovative, new or never been done or seen before. It is ‘boring’ to rehash the same topic constantly. This desire or need for novelty flows into how we fund ideas and how we publish scientific results.

To get funding to do research, scientists must apply for and receive grants. In the United States roughly 40 to 50% of the science R&D funding comes from either the federal or local and state governments (5,6,7). Requirements for federally funded grants mostly rely on building on previous work and coming up with new and innovative ideas that have not been done previously. For instance, the U.S. National Institutes of Health (NIH) requires proposed projects to be unique and cannot, by law, use taxpayer money to pay for research that is already done. While not bound by law, other funding sources outside of the government such as Alzheimer’s Association, The Heart Foundation and the Leukemia and Lymphoma Society all emphasize that the research funded by their grants be ‘novel’  in concept, approach, and or strategy. Everything proposed in these grant applications, for the most part, is new, innovative and assumes all prior work is correct and can be reliably built upon.

On the other end of the research pipeline is the publication of results. Like when a researcher is trying to get funding for their work, they must show novelty and innovation to get published. As examples, two top tier journals, Cell and Nature require that the research being submitted for publication is ‘novel.’ Cell states that they are looking for papers ‘that report results that prompt new thinking about a biological problem or therapeutic challenge—work that will inspire others to want to build on it.’ Nature has two criteria points that state the work must be ‘of extreme importance to scientists in the specific field’ and ’ideally, interesting to researchers in other related disciplines.’ These criteria obviously promote and result in good, high quality papers, but such policies also box out research publications that might be important but only conformational.

There are journals such as PLOS One that just look at the quality and rigor of the science itself as criteria for publication, but these types of journals are not nearly as common. PLOS One states: ‘Judgments about the importance of any particular paper are then made after publication by the readership, who are the most qualified to determine what is of interest to them’ and that the journal accepts studies with negative results. However, when ranking journals, using the standard Impact Factor rankings as of 2017, Nature and Cell come in at 10th and 22th respectively and PLOS Medicine (a sub journal of PLOS One and highest ranked PLOS One journal) is ranked 167th. It’s easy to see where a scientist would rather publish to advance their career considering most jobs and tenure track promotions look not just at the number, but the quality (impact factor) of scientific publications.

A few groups have been attempting to solve both the funding and the publishing issues described here. The Dutch Organization for Scientific Research, an organization in the Netherlands similar to the NIH in the U.S., has begun to fund grants for replication research (8,9). Grants can either be for reanalysis of the data already collected or can be a complete repeat of the study to confirm its results. This initiative by the Dutch helps on the front end of the science pipeline by specifically allocating grant money for repeating a set of experiments already done by other groups rather than doing the proposed conformational experiments with ‘extra’ money that was intended for innovative and new work. On the publication end of the scientific pipeline, there are foundations and groups of concerned scientists that are working on publishing replication studies (10,11). In addition, the PLOS One Biology journal has recently announced that it will take ‘scooped’ work as long as it is submitted within 6 months of the original article. As a well-articulated article in The Atlantic points out, this will help the first group that publishes by allowing the ‘second place’ group to confirm their results and thus add to the reproducibility of that original study. The “second place” group still receives recognition through publication of the work they likely spent months if not years doing and does not waste the money and resources on that work that would normally not see the light of day.

While the over emphasis of novelty by the scientific community is not the only reason for the ‘reproducibility crisis,’ it is part of the underlining culture that might be contributing to it. Other factors eluded to above such as the pressure to publish in high impact journals, variable cell and mouse lines, and lab personnel differences also contribute to the problem. The Dutch initiative, PLOS One Biology and Open Science Collaborations are all examples of ongoing projects and attempts to help solve part of this ‘crisis.’ Other ideas to further this effort to increase science reproducibility in the United States would be for a policy change at the NIH funding level. With a slight tweak to current policy, the NIH could allow for one of the specific aims of a grant to specifically verify something that is pivotal or groundbreaking in the field. This explicit allowance would start to make replication studies more acceptable and perhaps make researchers more apt to perform and publicly verify or dispute previous studies. Another idea would be for other journals to take PLOS One Biology’s lead and allow for ‘scooped’ research to be published. Depending on the prestige (impact factor) of the journal, the time frame of said ‘scooped’ research could be shortened from the 6 months of PLOS One and have more stringent review requirements. An additional policy that all journals could adopt that would greatly strengthen scientific confidence in pivotal papers is to attach short communications/addendums that show peer reviewed replication attempts of that work. These addendums would add to the strength of the original paper if conformational, or suggest there is more nuance and the need for further study if they do not confirm the original paper. All found in one place to boot!

Implementation of further replication policies would take a real push by the scientific community, but would beneficial to the ongoing efforts in trying to solve the ‘reproducibility crisis.’  While it may take time before we see any tangible or measurable results from the current endeavors, we should look to other ideas and concepts that enhance science reproducibility. We can’t afford to squander the public’s great faith in the scientific community due to highly touted papers that turn out to be a false positives or simply wrong.

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Written by sciencepolicyforall

April 25, 2018 at 9:32 pm

Old Wounds and Shifting Tides: Potential Consequences of and Remedies for Health Disparities and Inequity in the United States

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By: Calais S. Prince, Ph.D.

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By Jsonin [CC-BY-4.0], via Wikimedia Commons

By the year 2060, the percentage of racial and ethnic minorities is expected to increase by 49% in the United States. As the country becomes more diverse, it will become imperative to understand the genetic/epigenetic, molecular, cellular, and environmental differences associated with increased risk for disease onset. Currently, it is still clear that certain minority groups have a greater propensity for several diseases including diabetes, stroke, heart disease, and cancer. Health disparities are preventable differences in disease manifestation that can be attributed to social, political, and environmental factors. These factors can include, but are not limited to: discrimination, poverty, access to education, and exposure to hazardous chemicals.

Segregation in health care and the potential influence on participation in biomedical research

Although commonly perceived as a relic of the past, health care segregation in the United States persists and can be attributed to the Jim Crow laws that were designed and implemented following the Civil War through the 1960s. For example, “[m]any hospitals, clinics, and doctor’s offices were totally segregated by race, and many more maintained separate wings or staff that could never intermingle under threat of law” contributing to “subpar health care standards.” A glaring, present day example is that of Boston City Hospitals and Mass. General, which is both a reflection of the “the referral system that dates back five decades” and the type of care that will be covered by insurance. Another powerful, and personally relevant, example that demonstrates the importance of understanding how environment influences the risk for disease was discussed in a recent article. In African American/Black women, the consequences of racism had a significant impact on intrauterine stress as there are higher incidences of complicated pregnancies, miscarriages, premature births, and infant deaths which correlate with self-reported experiences with racism and discrimination. Conversely, African women were reported to have similar birth rates as Caucasian/White women. However, maternal health, pregnancy, and neonatal health of the grandchildren of African immigrant women born in the United States trend towards the patterns described in African American/Black women. These disparities are believed to contribute to the low percentages of minorities that participate in clinical and biomedical research as some of the barriers to participation are “distrust, provider perceptions, and access to care.” The cyclical nature of disparities: disparate living environments, disproportionate access to education and health care, postnatal complications, wealth inequalities, accelerated aging and morbidity, warrants a multifaceted solution to a pervasive, generational problem.

Mechanism that can potentially facilitate health care integration and improve participation in research

In 2010, the redesigned National Institute on Minority Health and Health Disparities (NIMHD) was established with a vision in which “all populations will have an equal opportunity to live long, healthy, and productive lives.” To accomplish this, NIMHD raises national awareness about the prevalence and impact of health disparities and disseminates effective “individual-, community-, and population-level interventions to reduce and encourage elimination of health disparities.” This vision recognizes the need to study health disparities within a variety of different modalities ranging from biomedical to social sciences as the majority of clinical and translational studies have been conducted in Caucasians/Whites. Specifically, there are four major NIMHD sponsored programs that provide funding to address the components of health disparities, inequity, and inequality at the levels of academe (Research Endowment Program), community (Community Based Participatory Research Program, Small Business Innovation Research/Small Business Technology Transfer Program), and internationally (Minority Health and Health Disparities International Research Training Program). It is also essential to facilitate mentoring of up-and-coming scientists and clinicians from underrepresented groups. The National Research Mentoring Network is a consortium composed of biomedical and clinical professionals that provide “evidence based mentorship professional development” for undergraduates through professionals; this serves as an important way to make inroads to increasing diversity in biomedical sciences. Earlier exposure to the sciences for underprivileged youth, as well as parental and community support, could serve as valuable avenues to combat health inequity.

Concluding thoughts: Demographic changes in the United States and the impact on biomedical research

The conversations surrounding disparities can be difficult, however, they are necessary. A concerted effort to improve the lives of those that are at risk/underserved have the potential to improve the lives of the individual as well as strengthen the scientific community. The projected increase of minorities in the United States warrants improved access to life saving treatment and encouragement of participation in biomedical research, as there is mounting evidence that environmental factors can influences the cellular and physiological response to stress. We also need to examine methodologies that will build trust in the scientific community which starts by: continuing to dismantle the remnants systematic discrimination, introducing science to underrepresented minorities earlier in their didactic training, providing community support, and train future researchers and clinicians to be more sensitive and responsive to the needs of the community in which they serve.

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Written by sciencepolicyforall

April 16, 2018 at 9:57 pm

Ask your doctor: This drug might be right for you

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By: Jennifer Patterson-West, Ph.D.

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source: Mike Licht via flickr

Direct-to-consumer advertising (DTCA) of prescription drugs is currently only legal in the United States and New Zealand.  In the United States, DTC advertising is regulated by the Office of Prescription Drug Promotion (OPDP) within the Food and Drug Administration (FDA).  The stated mission of the OPDP is to “protect public health by ensuring that prescription drug information is truthful, balanced, and accurately communicated.”

From patients to consumers

The first DTCA was a print ad for Pneumovax vaccine in 1981. A couple years later, the first broadcast advertisement aired for Rufen, a prescription brand ibuprofen.  In 1985, in response to initial DTCA, the FDA published a notice claiming jurisdiction over the regulation of DTCA. The FDA’s authority would hold DCTA to the same standards as previously established for advertisements to health care providers.  These standards required that advertisement contain a “fair balance” and “brief summary” that notes every risk described on the drug’s label.  Following the release of these standards, DTC print advertisements became prevalent with annual DTCA spending rising from $12 million (1980) to $340 million (1995).

The FDA loosened standards in 1997 by replacing the requirement of a “brief summary” with a “major statement” that only requires inclusion of the major risks associated with a drug and an adequate provision for consumers to obtain additional drug information, such as a toll-free number or website.  By no longer requiring drug companies to buy enough air-time to read the fine print, these new standards removed the fiscal constraint previously restricting the use of broadcast DTCA.  In fact, by the following year, annual spending on DTCAs increased to $1.2 billion annually and peaked at $5 billion in the mid-2000s.  It has been estimated, that on average, Americans now watch 9 drug advertisements per day, which equates to approximately 16 hours per year.  This level of contact far exceeds the amount of time patients typically spend with medical professionals.

Persuasive or informative? Are DTCAs truthful, balanced, and accurate?

Surprisingly, the debate around DTCA is balanced with respect to advocates and critics with considerable evidence supporting both positions.  However, the focus of those on the two sides of the debate differ considerable.  Advocates focus on the benefits associated with DTCA, whereas critics highlight examples of DTCA that are in direct subversion of established regulations and the stated mission of OPDP.

Advocates assert that DTCA empowers consumers by informing them about different treatment options, reduces associated stigmas, prompts dialogue with health care providers, and improves patient compliance.  Improved dialogue with healthcare providers is supported by a 2004 FDA survey in which 73% of physicians reported that they thought DTC advertisements helped patients ask more thoughtful question.  In the same survey, 77% of physicians declared that DTCA improved awareness of new drugs, whereas 33% of physicians agreed that the advertisements increased patient adherence.  In addition to these advantages, proponents suggest that DTCA drives competition, thereby reducing prescription costs.  However, no verifiable evidence is available to support this claim.

In contrast, critics proclaim that DTCA misinforms patients, medicalizes natural conditions, and strains patient-physician relationships.  In the same survey mentioned above, 60% of physicians believed that DTCA did not provide sufficient information regarding risks and 58% of physicians thought DTCA inspired patients to overestimate the efficacy of a particular drug.  These sentiments indicate that advertisements did not adequately communicate a balance of risk and benefit related information.  A recent study by Klara et al. found that 13% of ads within their study section suggested off-label uses, which are prohibited under current regulations. None of the evaluated ads quantified risk.  Another major critisim, is the medicalization of normal conditions such as hormonal changes associated with menopause or variability in sexual performance.  Proponents claim that medicalization heightens patient discontent with “symptoms” ultimately promoting the over utilization of pharmaceutical interventions that consequently contributes to rising medical costs.  Manufacturing of disease states is another example of advertisement practices that are in direct opposition of the stated OCPC mission which promotes the communication of truthful and accurate information.

The argument outlined by critics is likely contributing to the overall sentiment of physicians toward DTCA despite stated benefits.  In a 2013 survey by CMI/Compas that probed the opinion of physicians with respect to the current levels of DTCA, 52.9% supported a scale back, 18.3% felt it should be eliminated, 26% indicated that it should continue as is, and only 2.9% agreed with the expansion.

Maximizing benefit, while limiting risk

The unfavorable effects of DTCA can be lessened by the strict enforcement of current regulations and a careful assessment of advertisement strategies that interfere with truthful, balanced, and accurate communication of drug infomation.  However, since 2010, there has been a sharp decline in enforcement activity by the OPDP.  This decline follows the 2011 Supreme court ruling in Sorell v. IMS Health, which established that pharmaceutical marketing is protected under the Freedom of Speech Clause of the First Amendent.

Despite extensive critisms, it is unlikely that broad restrictions will be implemented in light of this and other juridical rulings that favor increased protection of commercial speech.  Additional measures have been proposed to minimize the risks associated with DTCA and maximize the benefits of engaging and educating consumers.  These include: (1) restricting advertisement of new drugs for a set number of years following approval, (2) pre-clearance of DTCA materials by the FDA or an unbiased entity, (3) mandating that all materials be presented at an 8th grade literacy level, and (4) requiring the inclusion of quantitative information regarding both the potential benefits and risks.  However, additional guidelines that focus on restricting or controlling the messaging of DTCA are unlikely to be upheld when they are challenged in court, due to the recently set precident.

An alternative approach to restrict DTCA has been focused on increasing the associated financial burden.  In 2002, U.S. Representative Jerrord Nadler (D-NY) introduced a measured called Say No To Drug Ads Act that would eliminate the use of tax deductions by pharmaceutical companies for DTCA costs.  Ultimately, this bill was not passed.  Recently, U.S. Representative Rosa DeLauro (D-CT) introduced the Responsibility in Drug Advertisement Act with a similar aim.  Although financial restrictions of DTCA are not in opposition to the constitution or current juridical rulings, this bill is also not expected to progress due to the current political climate.

Based on established precedents within the courts and the current political climate, mitigating the risk associated with DTCA may fall to consumer advocate groups or a public education campaign that informs patients about how to properly evaluate the risks and benefits of prescription drugs.  The success of FDA’s “The real cost” campaign emphasizes the potential benefit of public health campaigns and their impact on consumer behavior.

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Written by sciencepolicyforall

March 26, 2018 at 11:20 am

Posted in Essays

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Hold the Mayo: Supreme Court Ruling Blocks Patent Protection for Important Medical Diagnostics

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By: Jon Nye, Ph.D.

Essay_20180301

source: George Hodan, via publicdomainpictures.net

In President Obama’s 2015 State of the Union Address he announced the Precision Medicine Initiative. This study will follow 1 million or more volunteers over a long period of time at a cost of $215 million. The goal of this ambitious initiative is to fundamentally change the way we diagnose and treat patients by moving from a “one-size-fits-all” approach to one that tailors disease prevention and treatment based on each individual, factoring in differences such as genetic makeup, lifestyle, and environment. As we move forward into the era of precision medicine and gain a better understanding of the complex underlying mechanisms that contribute to disease, we will require the development of diagnostic tests that allow caregivers to identify the specific causes of each individual patient’s disease, leading them to select an appropriate treatment. Although the future market for diagnostic tests looks bright, recent Supreme Court rulings that will prevent companies from obtaining patent protection threatens to hamper the development of these important tools and may adversely affect patient care.

Mayo Collaborative Services v. Prometheus Laboratories

The purpose of the patent system is to encourage research and innovation by rewarding inventors with a temporary government-granted monopoly. This system has been around since the founding of our country and stems from Article I of the Constitution in which it says, “The Congress shall have power … To promote the progress of science and useful arts, by securing for limited times to authors and inventors the exclusive right to their respective writings and discoveries”. However, in the medical diagnostics field, recent court rulings have dramatically narrowed what is considered to be patent eligible. The most notable being the 2012 Supreme Court case Mayo Collaborative Services v. Prometheus Laboratories. This case centered on a method for determining the proper amount of a specific drug to give to patients by measuring the levels of a drug metabolite in their blood. This test provided a way to individualize dosing so that doctors could maximize the drug’s effectiveness while minimizing the side effects of receiving too much. In a unanimous decision, the Supreme Court ruled that this patent was invalid based on the fact that the test stated a “law of nature”.

“Prometheus’ patents set forth laws of nature – namely, relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm.”

In other words, any patent claim based on a test that measures compounds, metabolites, or any other marker specific to disease was now patent ineligible simply because they measure processes that occur in the human body. This extremely broad definition of what can be considered a natural law led to widespread rejection of most diagnostic tests, now referred to as a Mayo rejection.

Aftermath of the Mayo Decision

A recent study has analyzed the effect that the Mayo decision has had on the medical diagnostic patent landscape in the United States. In this study, the authors looked at 31 patents that contained either diagnostic or prognostic claims and were filed in both the US and the European Union. This revealed a huge discrepancy in the two systems. Indeed, in the EU, which has no legal equivalent to the Mayo rejection, 30 out of 31 applications had either received a patent or were still pending. On the other hand, 29 of 31 applications in the US were abandoned or were still pending after receiving a Mayo rejection. This study highlights the profound and possibly unintended consequences that the Supreme Court ruling in the Mayo case has had on medical diagnostic patent eligibility.

Surprisingly, recent federal court rulings have supported the notion that in the wake of Mayo, current guidelines are too restrictive and prevent even well-deserved new diagnostics from patent approval. Most notably was the recent case Ariosa Diagnostics, Inc. v. Sequenom, Inc. This case involved a patent on a new technique for non-invasive genetic testing of a fetus. Sequenom’s diagnostic relied on two novel findings. First, their test used fetal DNA that was found to be circulating in the mother’s blood which was previously discarded as useless. Second, they developed a method to selectively amplify DNA from the fetus apart from the mother’s by focusing on the paternal DNA contributions. Although this technique was referred to as, “a paradigm shift in non-invasive prenatal diagnosis”, by the Royal Society in the United Kingdom, multiple US courts ruled that it was patent ineligible based on Mayo. In fact, these court rulings were unanimous and all of the judges remarked that based on the Supreme Court’s guidelines their hands were tied, even though some judges believed that this novel test merited a patent. Judge Linn from the Federal Circuit Court wrote:

“This case represents the consequence—perhaps unintended—of that broad language in excluding a meritorious invention from the patent protection it deserves and should have been entitled to retain.”

These lower court rulings had many people hopeful that the Sequenom case would make it to the Supreme Court and allow them to refine the broad language in Mayo. However, the case was declined later that year, signaling that the solution to this problem was unlikely come from the courts. Instead, congress would have to act.

A Path Forward

In the wake of the Sequenom case, it was clear to many that the only way to change the restrictive patent guidelines in the medical diagnostic field was to pass legislation that would supersede the Supreme Court ruling. In order to gain momentum and start a discussion about what a bill like this would entail, a conference was held at Berkeley. It was attended by leading industry experts, scholars, policymakers, and a retired jurist. From these discussions, it was agreed that the current patent guidelines were inhibiting research and development in the diagnostics field by undercutting incentives. Consequently, at least in the bioscience field, the current system is no longer fulfilling the original intent of the patent system which was, “To promote the Progress of Science and useful Arts”. The consensus was that future legislation should expand patent eligibility to include conventional applications of scientific discovery. This general framework for a bill is consistent with current guidelines in the EU and also consistent with the spirit and intent of the patent system outlined in the Constitution. With the continued focus on tailored individualized treatment of patients it will be important to promote research and development in this area. Therefore, changing current guidelines should be a priority before they negatively affect patient health.

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Written by sciencepolicyforall

March 1, 2018 at 7:45 pm

Clinical Trials Policy Revision: For Better or Worse

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By: Jenn L. Nguyen, Ph.D., M.P.H.

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source: pixabay

As the largest public funder of biomedical research in the United States, the NIH wants to ensure that conducted trials are relevant to health priorities of the US, trials are conducted efficiently and are not duplicates of previously conducted trials, and trials contribute to scientific knowledge. In an editorial in 2016, NIH leaders noted a need for quality and efficiency improvements to clinical trials. NIH has introduced several initiatives, to enhance clinical trials stewardship by addressing accountability, transparency, efficiency, and dissemination. However, along with the widely acknowledged improvements some recent changes may hinder the pursuit of scientific knowledge.

To address accountability, all investigators and staff conducting and overseeing clinical trials must take the Good Clinical Practice (GCP) training. The training is mandatory for individuals involved with the design, conduct, oversight, or management of clinical trials. While the training may not be sufficient by itself, it does provide a standard of knowledge, a base of knowledge, standards, and guidelines for all clinical trials.

The second change requires that all grant applications for clinical trials be submitted under clinical trials specific funding opportunity announcements (FOA). Investigators interested in conducting a clinical trial can no longer submit under parent funding announcements, which made identifying clinical trials more difficult in the past. The FOAs will list specific review criteria for reviewers to consider clinical trials-related information, such as focus on the rationale, design, and operational and analysis plans. This new policy will increase NIH accountability and efficiency, as it will ensure that required information is submitted with each clinical trial application, allow staff to better track clinical trial proposals and study, and allow staff to uniformly apply appropriate review criteria.

A substantial change, however, is the limited eligibility of trainees to conduct interventional social science research, Institutional training (T) awards, which provide money to institutions for workforce training, do not allow money to be given to trainees involved in clinical trials (the exception is for D43s and K12s), Fellowship (F) awards, which support individual trainees,  do not support trainees involved in independently conducted clinical trials, but trainees can propose a research experience with a sponsor/co-sponsor.  For Career Development (K) awards, applicants may apply to either FOAs that specify “clinical trials required” or FOAs that are for “no independent clinical trials.” Scientists are concerned this may limit postdocs and students to get support for their fellowships and adequate career training.

To further address efficiency and accountability, applications must be submitted using a clinical trials protocol template that consolidates information from multiple forms, has structured data fields, and will collect information at the study level. This requirement will ensure that all investigators will submit the same information. In addition, the forms will contain fields forcing investigators to be clear and concise about their analytical and dissemination plans.

Addressing efficiency, NIH now requires use of a single Institutional Review Board (IRB) to review multisite studies. Prior, each institute involved with the study required duplicate or multiple IRB reviews, which involved the redundant assembly of experts to assure that the same proposed study was in line with the rights and protections of human and animal research subjects. Multiple reviews resulted in delays and at times, conflicting reviews. Guidance to establish a single IRB on record has been published.

Finally, there are significant changes for registration and reporting of clinical trials to address accountability, transparency, and dissemination. Investigators are now required to register their clinical trial(s) in the ClinicalTrials.gov database within 21 days of enrollment of the first participant. NIH makes the argument that this effort may help reduce the number of trials that fail, as it will require scientists to disclose their results even if the studies do not support their hypotheses urthermore, all investigators must adhere to the NIH policy on Dissemination of NIH-clinical trials. There have been longstanding concerns that investigators are not reporting all results (especially negative or non-significant results, not reporting results in a timely manner, and even sometimes, deviating from their own research protocol.

Along with these initiatives, The National Institutes of Health (NIH) broadened what was considered a clinical trial: “a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.” Adaption of this updated definition did not take effect until earlier this year and has alarmed some scientists. Clinical trials have been traditionally understood as experiments or observations for/in clinical settings to answer three questions: 1) Does the proposed treatment/intervention work? 2) Is the proposed treatment or intervention more effective than other treatments? 3) Are there side effects?

Scientists critical of the new definition first and foremost recognize and appreciate the motivation for NIH to increase transparency and replicability, specifically efforts for pre-registration, data sharing, and protocol sharing of trials. Yet, many scientists who conduct basic and behavioral research disagree agree that their work and studies should now be considered clinical trials. These scientists, and even scientific associations, remarked that the new clinical trials definition is too broad and traditional criteria to evaluate a trial might be inappropriately applied to their proposal. There is also concern that these changes will increase the administrative and bureaucratic burden for many scientists, specifically for exploratory scientists. To address and alleviate concerns, NIH released a set of case studies to help scientists identify and understand what is considered a clinical trial and must adhere to all the changes in the policy. While this effort provided clarification, many scientists are calling for NIH to hold further conversation with the extramural community.

While scientists recognize the need and laud NIH’s effort to address clinical trials stewardship, many of the same scientists are worried that these benchmarks set the wrong standards for success and rigor. Scientists are also worried about the additional administrative burden these changes will bring. As NIH enforces the policies, they have promised to monitor trouble issues and work with the community to find a solution without compromise.

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Written by sciencepolicyforall

February 20, 2018 at 3:52 pm

The impact of the growing student loan burden on graduate education

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By: Rebecca McPherson, Ph.D.

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source: pixabay

Every individual has his or her reason for pursuing a graduate degree. For many, a graduate degree is a path to a specific career; for others, it is simply a personal goal; and at times, it is a requirement for job advancement. Although the benefits of a higher degree are as numerous as the types of degrees and disciplines offered, there is one unifying theme across higher education: rising and often unavoidable student loan debt. Forbes reported that in 2017, the student loan debt in the U.S. had reached an astonishing $1.3 trillion. Of the 44.2 million U.S. borrowers with some type of student loan debt, over 2 million owe at or more than 100,000 dollars. At the top of this mountain of debt are U.S. graduate students, a quarter of whom will borrow close to $100,000 to complete their education,  while a tenth will end up borrowing upwards of $150,000.

Educational debt can extend beyond the typical student loan programs. While tuition poses a major cost to the student, many may not be able to make enough money through stipends or part-time work to meet their cost of living. The Report on the Economic Well-Being of U.S. Households in 2016-May 2017 showed an increase in the rate of borrowing for educational related expenses. Although student loans remain the primary source of borrower debt, credit cards, home-equity loans, and private loans also make up a portion of the total educational debt burden.

With a climate of ever-increasing educational costs and associated debt, many current, past, and future students are left asking, what is being done to curb the impact of mounting educational debt? The Institute for College Access & Success (TICAS) is responsible for enacting and overseeing the National Agenda for the Student Debt Policy in the U.S. Currently, TICAS focuses on risk-reduction strategies for student borrowers, including developing income-driven repayment plans, increasing access to Pell grants, and streamlining student borrower application processes.

The growing concern surrounding the ever-increasing student debt load is also being tackled at the state level. In recent years, several individual states have introduced policies aimed at protecting the student borrower, especially from predatory private student loan lenders. The Private Student Loan Transparency and Improvement Act was passed in Oklahoma in 2013 and requires private and alternate student loan providers to be transparent in the lending and repayment conditions. The state of Connecticut followed by being the first state to implement a borrower’s bill of rights in 2015. Several states offer student loan forgiveness and repayment incentives to entice student loan debt holders to work in specific regions.

What does the rising burden of student debt mean, and what are the ultimate costs to the borrowers? Ultimately, the price of student debt means that many young adults will have to put off major life decisions. Among graduate student borrowers, 43 percent state difficulty in regularly meeting student debt repayment obligations, 61 percent  say they are unable to save for retirement due to debt load, and 45 percent lack the means to save for an emergency fund. The costs of tuition has substantially increased since the early 1990’s and continues to grow; this initial rise in costs was caused by a decline in state support to colleges and universities.   Although there are no exact numbers showing the impact to low income students, the pursuit of a higher degree may, for many students, be out of reach.

Although several policies at both the state and national levels exist, there are gaps in how to deal with and resolve the mounting student debt crisis, and questions remain as to the impact on future training.  TICAS has indicated several areas of the lending and repayment process in need of continued improvement, such as enhancing educational tax benefits, preventing predatory lenders, and promoting student borrower awareness.

Students pursuing advanced degrees – beyond a bachelor’s degree – shoulder the bulk of the student debt burden. At times, wage outcomes fall below borrower expectations in certain fields of study. This can have a serious economic impact for borrowers who are unable to meet loan repayment requirements. Borrowers who have completed a higher level of education at a not-for-profit institute, and consequently have a higher burden of debt (i.e., $100,000 or more) are less likely to fall behind or default on payments.  Counter to this, student borrowers who have attended a for-profit institute or did not finish their degrees are more likely to fall behind on repayments or default on their student loans.  Additionally, those seeking advanced degrees will find that they have a greater ability to borrow from the federal loan program, which often has high caps and few or no credit checks required before borrowing. This leads some to put the blame for the student debt crisis on the federal government, arguing that unchecked borrowing causes educational institutions to continually raise tuition and fees for graduate education.

As of February 2018, no new federal laws regarding the student loan debt burden have been passed. However, several initiatives have been proposed by the current administration in an effort to tackle the expanding costs of the student debt. One such recommendation is the expansion of the income-based repayment plan (IBR), which would consolidate all loans into a single repayment of 12.5 percent of income with loan forgiveness after 15 years. Other recommendations include lowering federal loan interest rates; eliminating the Public Service Loan Forgiveness (PSLF) program, which would instead give focus to the proposed IBR; and a pushing for tuition reduction by imposing educational institutes to cut administrative costs.  On the upcoming 10 year anniversary of the start of PSLF, many argue that cutting the program would dissuade many young professionals from entering into the lower paying public health service.

Ultimately, the impact of the student loan debt burden may negatively affect graduate level training. There are calls to protect borrowers from predatory lenders and proposed legislation to tackle the debt crisis. The willingness to take on large debt and possibly delay major life decisions lies with the individual. For now, the student debt debate continues.

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Written by sciencepolicyforall

February 6, 2018 at 12:13 pm

How do healthcare and health outcomes in the US compare to those of other developed countries?

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By: Vanessa Gordon-Dseagu, PhD

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source: pixabay

For much of 2017, the Trump administration engaged in numerous attempts to repeal the Affordable Care Act – legislation that was considered by many to be the first step towards the introduction of universal healthcare within the US. As the debate continues over the role of the government in the provision of healthcare, comparisons with systems abroad may reveal important shortcomings within those found in the US. There are a number of methods to assess and compare the performance of a healthcare system; this essay focuses upon the key areas set out by the Peterson-Kaiser Health System Tracker – spending and health outcomes (those amenable to health-service provision) as well as the uninsured/access. By looking at the provision of healthcare internationally, we may learn key lessons in how to improve the US system.

Cost

In 2016 the US spent around 17% of its GDP on healthcare (around $3 trillion). This is almost double the amount spent by other industrialized nations, while the amount of healthcare used per capita is similar across countries. The key reason for this appears to be cost. Patients in the US pay far more for their healthcare to be provided than their international counterparts, with one study finding hospital prices in the US to be 60% more than those in Europe. One reason for this appears to be the high cost of insurance administration within the US system caused by, oftentimes, fractured and duplicative provision. Hospitals must employ large departments to properly bill insurance companies and verify insurance coverage, costs that are passed on to the patient. In comparison, nationally or regionally organized systems, free at the point of need, do away with the need for insurance administration. The Affordable Care Act (ACA) sought to address some of the administrative waste and duplication found within US healthcare provision by employing economies of scale and streamlining the insurance procedure.

The cost of prescription drugs in the US is also an issue for concern for patients and policy-makers alike. The US spends more per capita on prescription drugs than other countries within the Organization for Economic Cooperation and Development (OECD). A 2016 JAMA study found that per capita spending on prescription drugs was $858 a year within the US, compared with $400 for 19 other industrialized countries. One factor likely influencing this is the more rapid uptake of new and, thus, more expensive prescription drugs within the US compared with other OECD countries. While an equally important factor is the price at which the drugs are sold in the US compared to other countries – drug prices in the US are substantially increased compared with other markets. The experience internationally is that policies, such as centralized pricing and universal healthcare, as well as other price controlling strategies, are effective at reducing drug costs. While the majority of developed countries enact some form of price regulation, within the US, the federal government is legally prohibited from negotiating drug prices for its widely administered Medicare program. Further to this, for each new drug the US Food and Drug Administration approves, it upholds a market exclusivity period, ranging from six months to twelve years, in which it will not approve a generic form of the same drug, limiting access to cheaper generic drugs. This, combined with US patent law protections, means that, on average, a brand-name drug manufacturer can expect their product to be on the market between 12-16 years before  the introduction of generic competitors. In comparison, across Europe 13 countries have policies which make generic drug substitution mandatory, 13 have voluntary protocols, with only five forbidding the practice.

The uninsured and access to healthcare

The World Health Organization considers universal health coverage to be a system within which 1) individuals can use the health services they need; 2) the care is of a sufficient quality to be effective; 3) individuals are not exposed to financial hardship caused by accessing the services. Of the 35 countries within the OECD, 32 have healthcare legislation that is in keeping with the WHO definition of universal healthcare. The US is now the only high-income country not to offer universal health insurance coverage.

Although the introduction of the ACA reduced the number of uninsured in the US from 44 million in 2013 to a low of 28 million in 2016, by the end of 2017 the number of uninsured had again risen by 1.3%, an estimated 3.2 million individuals. The causes of this increase may relate to the uncertainty surrounding the potential repeal of the ACA under the current administration, the repeal of the individual mandate within the Trump tax bill, the exit of several insurers from the ACA market and increasing health insurance costs.

The benefits of healthcare coverage upon health outcomes are well documented and relate to access to preventive, ambulatory, primary and secondary healthcare. Further to this, access to healthcare is particularly important for those with complex or ongoing chronic conditions. A review of the evidence related to health insurance coverage and health concluded:

“There remain many unanswered questions about U.S. health insurance policy, including how to best structure coverage to maximize health and value and how much public spending we want to devote to subsidizing coverage for people who cannot afford it. But whether enrollees benefit from that coverage is not one of the unanswered questions. Insurance coverage increases access to care and improves a wide range of health outcomes. Arguing that health insurance coverage doesn’t improve health is simply inconsistent with the evidence.”

To overcome some of these issues, members of the House of Representatives (with a parallel bill introduced in the Senate in 2017) have been developing the Expanded & Improved Medicare for All Act, colloquially known as ‘Medicare for all’. The bill seeks to take the role of government in healthcare one step further than the ACA and introduce:

“A system in which a single public or quasi-public agency organizes health care financing, but the delivery of care remains largely in private hands. Under a single-payer system, all residents of the U.S. would be covered for all medically necessary services, including doctor, hospital, preventive, long-term care, mental health, reproductive health care, dental, vision, prescription drug and medical supply costs”.

Health outcomes

In relation to access, the US system has been found to fall short, particularly in the areas of primary care, prevention and management of chronic conditions. In its comparison of healthcare systems, the Commonwealth Fund concluded that the US ranked last on access. The insufficiencies of these areas of care contribute to the lower life expectancy found within the US compared with the majority of OECD countries – in their 2016 report, the US was found to rank 26 out of the 35 OECD countries. The same investigation found that the US also fell below the OECD average in several more nuanced indicators of health (for example maternal and infant mortality). In the same study undertaken by the Commonwealth Fund, the US ranked last out of 11 comparable countries for healthcare outcomes. The report also found that the US had the highest rate of mortality considered amenable to the provision of care. Compared with the other 10 countries under investigation, the US performed better in areas such as in-hospital mortality following a cardiovascular disease related event and five-year survival for some cancers. The lack of easily available preventative services may also contribute to the high, and increasing, rates of non-communicable diseases such as diabetes, as well as other conditions such as overweight and obesity, for which the US has the highest rates within the OECD.

Despite the substantially increased costs of healthcare in the US compared with international counterparts, the population is not experiencing a corresponding improvement in health outcomes. International comparisons suggest that tighter regulation of costs, particularly those related to insurance administration and prescription drugs, may go some way to addressing this issue. The introduction of universal coverage is also likely to allay some of the deficiencies inherent to healthcare provision within the US. How the issue of the provision of healthcare is broached by this, and future, administrations will have a substantial impact upon the health of the nation.

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Written by sciencepolicyforall

February 1, 2018 at 11:42 am