Science Policy For All

Because science policy affects everyone.

Posts Tagged ‘FDA

How the COVID-19 pandemic response fits into a national security framework

leave a comment »

By Lynda Truong, PhD

Image by fernando zhiminaicela from Pixabay 

What began as mysterious cases of pneumonia in Wuhan, China in late December escalated into a global pandemic in a matter of just a few months. By the end of January, cases had been reported in 18 countries and the disease was declared a Public Health Emergency of International Concern by the World Health Organization (WHO). In March, the WHO officially raised COVID-19 to pandemic status. By this time, there were already more than 118,000 cases and over 4,000 deaths reported worldwide. At the time of writing this article, there have been over 1.4 million confirmed cases of COVID-19. Countries across the world are experiencing unprecedented disruptions in their health, social, and economic systems. Italy has seen its hospitals completely overwhelmed. China and several other countries have implemented strict quarantine protocols. US stock markets have plummeted 20% and over 17 million Americans have filed for unemployment. To date, there have been over 14,000 COVID-19 related deaths across the US, over 6,000 of which were in the state of New York alone. When compared to the 2,977 deaths following the attacks on 9/11, the urgent need for action becomes quickly evident. Given the rapid spread of the virus and its far-reaching negative effects, addressing pandemics as a matter of national security can provide an effective model for preparation, prevention, and mitigation.

In response to the 2001 anthrax attacks, President George W. Bush passed Homeland Security Directive 10: Biodefense for the 21st century in 2004. While the focus of his directive was the prevention of biological weapons attacks, biodefense strategy has since been expanded to include natural outbreaks of disease. The connection between global heath and national security was initially proposed in 2005 to raise awareness for the HIV/AIDS pandemic, and helped provide much needed funding and resources to combat the spread of the disease. The global health / security connection became apparent again during the Ebola epidemic in West Africa in late 2014, when President Barack Obama deployed 2,800 military personnel and allocated over $2.3 billion in aid. At that time, cases had already spread to Dallas and New York City. However, as a result of the administration’s quick action and the international cooperation of several countries, the transmission of the disease was contained in West Africa by January 2015 and transmissions had slowly decreased to zero by the end of the year. 

While President Donald Trump has received much criticism for restructuring the Global Health and Security Biodefense team, global health and pandemic preparedness has remained a recognized issue within the National Security Council (NSC) under the current administration. In 2018, the NSC established the National Biodefense Strategy, which outlines several objectives for preparing and responding to naturally occurring or deliberate biological threats. These include, but are not limited to: promoting domestic and international biosurveillance to aid in the prevention and rapid detection of new threats, strengthening global health security to prevent local incidents from becoming epidemics, and ensuring a strong public health infrastructure. While the document clearly addresses the need for pandemic preparedness, it does not delineate specific responsibilities amongst various federal agencies and the plan for implementation was still under development when the COVID-19 outbreak began. 

Due to growing trends in globalization, an epidemic in a distant area of the world can have severe consequences within the US if left unchecked. The spread of infectious disease domestically has a direct impact on the health and well-being of citizens and can overburden existing healthcare systems. A growing population of sick or panicked citizens can result in disruptions in local and national supply chains for essential medical supplies, food, or other basic necessities. As the pandemic escalates, these effects will impact businesses, leading to unemployment and pushing the economy toward a recession. The recent spread of COVID-19 exemplifies many of these consequences, and the rapid development of events provides little room for error or hesitation when implementing counteractive policies. 

The current administration has enacted policies intended to aid or accelerate the development of medical and pharmaceutical supplies. While these are direct and effective solutions, they require time. Although several companies are racing to develop a vaccine for COVID-19, the creation of a safe and effective vaccine for public use is likely at least a year away, even with the support of federal agencies to expedite clinical trials. Until a vaccine is available, public/private partnerships can focus on the development and manufacture of diagnostic tests, medical devices, and personal protective equipment (PPE). Singapore, Hong Kong, and other east Asian countries have managed to control the spread of COVID-19 by implementing early diagnostic testing, while a reliable test is still not widely available in the US. The Strategic National Stockpile, the country’s largest reserve of medical supplies for use in public health emergencies, is nearly depleted less than three months after the US reported its first case of COVID-19. President Trump has already invoked the Defense Production Act, directing several companies to manufacture ventilators and N95 medical masks to address current shortages. Until medical and pharmaceutical solutions are more readily accessible, there are also a number of mitigation strategies available. Border screening and quarantine are effective methods for delaying the spread of the coronavirus to prevent inundating the healthcare infrastructure. Countries, such as China, have slowed the spread of new cases by implementing a mandatory national lockdown. Throughout the US, many states have been closing all nonessential businesses and strongly encouraging, if not mandating, social distancing. 

As with any national crisis, it is essential to have clear and strong leadership during a pandemic. The past few weeks have seen a disjointed and inconsistent adoption of policies throughout the US. While all states have now declared a state of emergency, the implementation of policies such as nonessential business closures and mandated quarantine have varied widely by state. A centralized effort between federal and state governments would mitigate viral spread more thoroughly than disunited policies and avoids unnecessary confusion during a turbulent period. Effective communication and transparency are also paramount to establishing public trust and facilitating compliance with local and federal guidance. President Trump is now warning of the severity of the spread of COVID-19, but still tempers that message with the desire to reopen businesses soon. Such mixed signaling risks inciting more confusion in an already turbulent time. In the modern age of social media, the accidental or deliberate spread of misinformation can endanger public health, and the dissemination of scientific, evidence-based facts by government and medical authorities is especially critical. 

Despite the national security implications of pandemics, framing global health as a matter of defense and security should be approached with caution. Pandemics will always be an issue of public health, and as such require expertise from epidemiologists and infectious disease experts as much as it requires input from defense strategists. Additionally, drastic measures such as mandatory lockdown and border control may prove necessary in extreme circumstances, but institutionalizing such methods risk infringing on civil liberties. In response to COVID-19, Hungary’s parliament has introduced a set of measures that allow prime minister Viktor Orbán to rule by decree for an indefinite period. In the Philippines, President Rodrigo Duterte has been granted an extension of emergency powers and has ordered military officials to shoot violators of the national lockdown. In contrast, many countries such as Singapore, South Korea, and Taiwan have successfully implemented aggressive and targeted quarantine measures, in combination with a number of other policies, without overreaching government authority or threatening human rights. In the face of crisis, the necessity of public health can and must be appropriately balanced with a commitment to human rights. 

Pandemics also present a number of national security risks on an international stage. Disease can have direct impacts on the health of diplomats, foreign officers, and military personnel, potentially jeopardizing any standing plans or activities abroad. If not contained, widespread disease and fatalities can also lead to international unrest and instability in vulnerable nation states. If the US is unable to manage the spread of the disease domestically, it will not have the resources to aid allies or other nations, which can negatively affect US influence abroad. During the Ebola epidemic, the US actively provided expertise, supplies, and leadership in a time of crisis. In contrast, China was at the front of the COVID-19 pandemic and has seemingly now been able to contain the spread of the disease. It has sent supplies and experts abroad to 120 countries, as many other countries continue to grapple with increasing cases of COVID-19. Furthermore, US influence is already experiencing resistance as the administration is coming under increasing pressure to lift sanctions against Iran in the wake of COVID-19. In fact, a number of EU countries have already taken steps to bypass these sanctions in order to deliver critical medical supplies to Iran

In order to adequately address the national security risks posed by pandemics, international frameworks and collaborations must be established. Biosurveillance is a key approach in preventing the spread of infectious disease. Data sharing is imperative, and misleading information can cause governments to develop inadequate, or even harmful, public health strategies. China’s early suppression of information surrounding COVID-19 cost valuable time. If countries battling epidemics are reluctant to solicit aid or provide data, diplomatic international pressure may suffice to elicit a response. Failing this, intelligence communities could offer valuable information, and it may be prudent to provide technical training or expert input to help intelligence officers accurately interpret medical data. Still, the best resolution of an epidemic is to contain it at the source, and this requires international cooperation. The costs of a global pandemic far outweigh the cost of international aid if the epidemic can be contained. The US is estimated to have spent approximately $2.3 billion in fighting the Ebola epidemic in West Africa, which is three orders of magnitude less expensive than the critical $2.2 trillion stimulus package recently passed in Congress.

Modern trends in globalization, urbanization, and population growth make epidemics more difficult to contain and a pressing threat to national and global security. Recent events surrounding the international spread of COVID-19 provide a glimpse of the severe impact a pandemic can have and a useful case study for how a national security framework can be used to help prevent or mitigate future pandemics. Within the US, pandemic preparedness has remained a keystone of the national biodefense strategy. Some priorities, such as the focus on developing and delivering pharmaceutical solutions are well recognized. However, the spread of COVID-19 highlights a need for a more centralized and cohesive response within the US and a more collaborative and faster response abroad. A detailed implementation plan addressing these gaps would serve to better inform future decisions and leadership and help protect national security.

Written by sciencepolicyforall

April 10, 2020 at 3:18 pm

Evolution of FDA Diagnostic Testing Policies in the Changing Landscape of the COVID-19 Pandemic

leave a comment »

By Emily Phung, PhD

Image by Gerd Altmann from Pixabay

In the United States, the Food and Drug Administration (FDA) regulates the development and marketing of commercial tests. In vitro diagnostics (IVD) inform healthcare workers how to help cure, treat, or prevent diseases. These devices go through an extensive submission process which can take several months for approval. During this timeframe, the tests are evaluated for their safety, effectiveness and risk level based on their intended use.

If there are no available alternatives, unapproved medical products (including diagnostic kits and personal protective equipment) can be rapidly approved by the FDA through an Emergency Use Authorization (EUA) to diagnose, treat or prevent life-threatening conditions in times of chemical, biological or nuclear threats. However, an EUA is not a pathway to permanent marketing. Companies that wish to sell their device or diagnostic must file a premarket submission in order to legally market their product after termination of the EUA. For example, in response to the Zika virus in 2016, the FDA authorized 15 diagnostic tests for Zika. After termination of the EUA, three of those tests underwent premarket submission and gained full FDA clearance.

When posed with an emerging health threat, the Centers for Disease Control and Prevention (CDC) is the first to develop a diagnostic test in the United States. COVID-19 is an infectious disease that infects the respiratory tract. Therefore, diagnostic kits use the reverse transcription polymerase chain reaction (RT-PCR) technique to detect the presence of the SARS-CoV-2 virus (the infectious agent the causes COVID-19) in upper and lower respiratory specimens (such as nasopharyngeal swabs, bronchoalveolar lavage and lower respiratory or nasal aspirates) collected from the patient. With the high transmission rate of SARS-CoV-2, it is crucial to make diagnostic kits widely available to contain the spread of the virus. 

In light of the COVID-19 pandemic, the FDA has justified the emergency use of IVDs for the detection and diagnosis of COVID-19 through an EUA. The FDA issued several new policies for COVID-19 diagnostic tests in order to rapidly expand to availability of testing kits in the United States. The first policy was issued on February 4th, 2020 and expanded the use of the CDC’s RT-PCR test to CDC-qualified labs. This policy was the first step to expedite the availability of diagnostic kits to labs outside of the CDC. On February 29th, 2020, the FDA issued a second policy, which granted more flexibility around the development of diagnostic tests. Specifically, this allows facilities certified under the Clinical Laboratory Improvement Amendments (such as most hospital labs) to develop and use their own COVID-19 tests based on FDA guidelines. However, labs that wish to develop their own diagnostic are still required to fill out an EUA and must validate their tests by sending five positive and five negative samples to a qualified lab for confirmation.

On March 16th, the FDA began allowing state laboratories to set up their own systems of authorizing diagnostic tests. Because state laboratories will be engaging directly with state authorities instead of the FDA, they do not need to submit an EUA. Furthermore, an extension of the February 29th policy allows manufacturers that have internally validated their COVID-19 diagnostic tests to immediately start distributing their tests to other laboratories, as long as they provide clear instructions for use and share data of the test’s performance characteristics on their website. The manufacturers are still required to submit an EUA within 15 days of validating their diagnostic test. 

Finally, the latest update provided guidelines on the development of serological tests for COVID-19. Serological tests can measure the level of antibodies, which are proteins in the blood produced in response to an infection. Because it takes about two weeks for the immune system to start producing antibodies after a first exposure to a pathogen, serological tests cannot distinguish between a recent or past infection and are not meant to diagnose or inform COVID-19 infection status. However, serological tests can differentiate whether or not individuals have had a history of exposure to SARS-CoV-2 and determine how long immunity will last. These results are essential to inform long-term decisions about lifting stay-at-home orders and reopening schools and businesses.

As of March 31st, 2020, the FDA issued 22 in vitro diagnostic EUAs for SARS-CoV-2 testing. These FDA policies will expand testing capabilities in laboratories across the United States and increase surveillance. The guidance for serological tests offers a solution to determine how society can return to normalcy after the pandemic is over. Together, these efforts can bolster the public health response and help inform the development of upcoming policies regarding SARS-CoV-2 in the United States.

Written by sciencepolicyforall

April 3, 2020 at 3:01 pm

Posted in Essays

Tagged with , , , ,

Targeting the spread of unregulated Stem Cell and regenerative therapies

leave a comment »

By: Kellsye Fabian, PhD

Image by Darko Stojanovic from Pixabay

Advances in regenerative medicine research have generated significant public interest in therapies that have the potential to restore the normal function of cells, tissues and organs that have been damaged by age, disease, or trauma. Investment and enthusiasm in this field have propelled the development of regenerative therapies such as cell therapy, bioengineered tissue products, and gene therapy. While several hundreds of these treatments have progressed to clinical trials, the Food and Drug Administration (FDA) has approved only a few regenerative therapies. Of these, most are stem cell-based products derived from umbilical cord blood used to treat blood cancers and immune disorders, and three are gene therapies to treat cancer or blindness. 

Alarmingly, an increasing number of businesses and for-profit clinics have been marketing regenerative therapies, mostly stem cell products, that have not been reviewed by the FDA. In 2016, there were 351 stem cell businesses offering interventions that could be administered in 570 clinics. That number was estimated to have doubled in 2018. Most of these establishments tout that their products can treat or cure serious illnesses and/or provide a wide range of benefits. These claims are often unsubstantiated. Moreover, these unapproved interventions pose a great danger to patients and have resulted in serious complications including blindness, infections, cardiovascular complications, cancer and death.

 Some patients remain willing to take the risks, especially those with serious diseases who have exhausted all possible conventional treatment or those that may be searching for alternative therapies. These individuals often fall prey to the overly optimistic portrayals of stem cell products in the media advertisements from stem cell companies. 

For years, these unscrupulous businesses have avoided heavy regulations. Physicians, researchers and ethicists, have urged for stricter monitoring of regenerative therapies as the commercial activity related to these interventions expanded. In response, the FDA has increased its oversight of the field and has issued guidance relating to the regulation of human cells, tissues and cellular or tissue-based products (HCT/Ps) to ensure that commercialized regenerative therapies are safe and are founded on scientific evidence.

FDA increased oversight 

Since 2017, the FDA has increased oversight and enforcement of regulations against unscrupulous providers of stem cell products. In 2018, the FDA sought permanent injunctions against two stem cell clinics, California Stem Cell Treatment Center Inc and Florida-based US Stem Cell Clinic LLC, for selling unapproved stem cell products and for significantly deviating from current good manufacturing practice requirements that ensure the sterility of biological products. 

The case against California Stem Cell Treatment Centers began in August 2017, when the US Marshals Service, on behalf of the FDA, seized five vials of smallpox virus vaccine from a clinic affiliated with California Stem Cell Treatment Centers. The vaccine was provided by a company called StemImmune and was being combined with stromal vascular fraction (SVF), which are cells derived from patient adipose (fat) tissues that consists of a variety of cells, including a small number of mesenchymal stem cells. This combined product was then administered to cancer patients in California Stem Cell Treatment Centers intravenously or through direct injection into patients’ tumors. 

Cancer patients have potentially compromised immune systems and the use of a vaccine in this manner could pose great risks, such as inflammation and swelling of the heart and surrounding tissues, to the patients. In addition, California Stem Cell Treatment Center provided unapproved treatments to patients with arthritis, stroke, ALS, multiple sclerosis, macular degeneration, Parkinson’s disease, COPD, and diabetes. The injunction case against California Stem Cell Treatment Center is still pending.

US Stem Cell Clinic also marketed SVF to patients seeking for treatment for conditions such as Parkinson’s disease, amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), heart disease and pulmonary fibrosis. Three women with macular degeneration, an eye disease that causes vision loss, went blind after receiving eye injections of SVF products from US Stem Cell Clinic. Following these events, in June 2019 a Florida judge ruled that the FDA is entitled to an injunction against US Stem Cell Clinic, meaning that the FDA has the authority to regulate them and stop them from providing potentially harmful products.

While this decision strengthened the position of the FDA as a regulatory body for regenerative medicine, businesses have found different tactics to continue selling unapproved products. After the court ruling, US Stem Cell Clinic stopped selling the fat-based procedure. However, it said that it would continue to offer other stem cell treatments. Instead of stem cells derived from fat, which was the topic of the injunction, the company would now harvest cells from patients’ bone marrow and other tissues to “treat” different conditions. Another company, Liveyon, was given a warning by the FDA in December of 2019 for selling unapproved umbilical-cord blood-based products that were tied to life-threatening bacterial infections. Liveyon has since halted the distribution of its products in the US but has opened a clinic in Cancun, Mexico where it has continues “treating” patients outside the scope of the FDA. Other companies have changed their terminology and marketing language to escape the FDA crackdown against stem cell clinics. Instead of using the phrase “stem cells” in their websites and advertising, they now use “cellular therapy” and “allografts.”

The FDA’s Regulatory Framework for Regenerative Medicine

The warnings and injunctions filed by the FDA against the aforementioned stem cell businesses were in conjunction with the comprehensive policy framework for regenerative medicine that the agency announced in November 2017. The policy framework aims to clarify which medical products are subject to the agency’s approval requirements and to streamline the review process for new regenerative therapies. 

In the case of cellular and tissue products/procedure, there is often a gray area concerning what should be considered medical products, which are under FDA oversight, and what should be considered an individualized treatment being performed by a doctor within their medical practice, which is not regulated by the FDA. Stem cell clinics have often used this ambiguity as justification to sell products without FDA approval. According to the new guidelines, for cells and tissue to be exempt from FDA regulation, several criteria should be met: 1) they must be taken from and given back to the same individual during the same surgery, 2) they must not undergo significant manufacturing (minimal manipulation), 3) they must perform the same basic function (homologous use) when re-introduced to the patient, 4) they must not be combined with another drug or device, and 5) the benefits and risks must be well understood. If any of these criteria are not met, the cell or tissue is considered a drug or biologic and is subject to pre-market review of the FDA. Some ambiguities still persist in the current form of the policy, such as what constitutes “minimal manipulation” and how to address nonhomologous use (i.e. the cells or tissues are used in ways other than its original function). The guidelines are an important starting point in determining which therapies are under the FDA’s purview and continued dialogue between the FDA and stakeholders involved in product development will provide more clarity about how products will be classified.

The policy framework also addresses how the FDA aims to implement the regenerative medicine provisions of the 21st Century Cures Act. Signed into law in 2016, the Cures Act is designed to expedite the development and review of innovative medical products. One of the new programs under this law is the Regenerative Medicine Advanced Therapy (RMAT) designation. A product is only eligible for RMAT designation if 1) it is a cell therapy, therapeutic tissue-engineering product, HCT/P, gene therapy, or combination product using any such therapy; 2) it is intended to treat, modify, reverse, or cure a serious condition; and 3) preliminary clinical evidence indicates that the therapy has the potential to address unmet medical needs for such condition. Stakeholders involved in product development strongly support the creation of this expedited review program. Meanwhile, others are concerned that the RMAT designation will lead to the approval of therapies based on fewer or smaller studies and, hence, treatment-related adverse events would emerge only after a product is on the market. But since RMAT therapies are intended to treat serious conditions, the risks may be acceptable and may be outweighed by the benefits to the patients. Nevertheless, postmarket studies would be essential and must be required to ensure the safety and efficacy of RMAT therapies. 

The establishment of these policy frameworks are definitely a step towards better regulation of the unbridled regenerative therapies. The increased enforcement of these new guidelines will hopefully dissuade unscrupulous businesses from taking shortcuts while encouraging legitimate companies to develop novel treatments. This will ensure that regenerative medicine will continue to be an exciting field that has the potential to provide innovative treatments that will improve human health. 

Have an interesting science policy link? Share it in the comments!

Written by sciencepolicyforall

January 24, 2020 at 7:36 pm

Science Policy Around the Web December 20th, 2019

leave a comment »

By Mohor Sengupta, PhD

Image by Eveline de Bruin from Pixabay 

Trump Administration Takes First Step to Allow Drug Imports From Canada

“For the first time in history, H.H.S. and the F.D.A. are open to importation as a means to lower drug prices,” Alex M. Azar II, secretary of HHS said recently. In a step unusual for the Trump administration, it has announced that import of drugs from Canada would be made possible. Despite vehement opposition from the pharmaceutical industry, and previously from even the FDA, the government is set to implement importing of drugs from outside the U.S., once the states have come up with individual proposals for approval by the federal government. 

The proposed implementation is still a long way off. The pharmaceutical industry’s main lobbying group, the Pharmaceutical Research and Manufacturers of America, are not happy with the recent turn of events. “At a time when there are pragmatic policy solutions being considered to lower costs for seniors at the pharmacy counter and increase competition in the market, it is disappointing the administration once again put politics over patients,” the group’s president and chief executive, Stephen J. Ubl, said in a statement.

Because a proposal such as this has never been implemented before, the Trump administration is unsure of the costs it would incur. Until the states submit their individual plans of how to go about implementing these imports, estimates of consumer or taxpayer savings cannot be made. However, it is amply clear that consumers of highly priced drugs will be happy with the move. In recent years, public outrage over high prices of prescription drugs has mounted steadily and lowering drug prices by importing them would meet a key campaign promise of the administration.

A 2003 law sets limits on the types of drugs that can be imported, and by that law, most of the expensive drugs, including insulin, biologics and injectable drugs, are excluded from this proposal.  

(By Katie Thomas, New York Times)

Written by sciencepolicyforall

December 20, 2019 at 3:57 pm

Science Policy Around the Web December 17th, 2019

leave a comment »

By Mary Weston, PhD

Source: Wikimedia

E-cigarettes linked to lung problems, first long-term study on vaping finds

The first study evaluating long-term health effects of electronic cigarettes (e-cigarettes) has found that vaping increases the risk of developing a chronic lung disease. 

Researchers tracked the smoking habits and health of over 32000 U.S. adults who, at the beginning of the study, showed no signs of lung disease. After monitoring for only three years (2013-2016), they found that those who used e-cigarettes were more likely to develop a chronic lung disease compared to non-users. These respiratory diseases include asthma, bronchitis, emphysema, and chronic obstructive pulmonary disease (COPD). 

Adults who smoke combustible cigarettes had a higher chance of developing lung diseases compared to e-cigarettes, but many adults tend to use both forms of tobacco, an activity which compounds disease threat. “The risks of e-cigarettes and cigarettes are independent of each other, and so if you’re a dual user — meaning you’re smoking and using e-cigarettes at the same time — you have the risks of smoking multiplied by the risks of e-cigarette use,” said one of the study’s authors Stanton Glantz

Specifically, the odds of an e-cigarette user acquiring a respiratory disease increased by a factor of 1.3, combustible smokers saw an increase in 1.6, and dual users were 3.3 times more likely to develop a disease.  

In this study, the surveyed participants self-reported their habits and health conditions, which may lead to recall bias and could have influenced the researchers’ results/conclusions. However, this paper contributes to increasing evidence that vaping can cause physical harm, including lung tissue chemical burns and clogs from the carrier oil vitamin E acetate. Further, this research did not include a separate form of vaping-related illnesses, EVALI (e-cigarette or vaping associated lung injury), an outbreak that is still not completely understood, but has affected more than 2400 people and caused 52 deaths as reported by the CDC

(Ericka Edwards, NBC News)

Written by sciencepolicyforall

December 17, 2019 at 9:49 am

Science Policy Around the Web December 10th, 2019

leave a comment »

By Kellsye Fabian MS, PhD

Image by allinonemovie from Pixabay 

Two New Drugs Help Relieve Sickle-Cell Disease. But Who Will Pay?

The FDA recently approved two new treatments for sickle-cell disease — Adakveo and Oxbryta. Sickle-cell disease is caused by a gene mutation that results in abnormal hemoglobin and sickle-shaped red blood cells. These cells clump together, restricting the flow in blood vessels and limiting oxygen delivery to the body’s tissues. This leads to severe pain and organ damage. Adakveo, made by Novartis, can prevent occurrence of bouts of severe pain caused by misshapen blood cells getting stuck in blood vessels. Oxbryta, made by Global Blood Therapeutics, can prevent disease-induced anemia that can result in permanent damage to the brain and other organs. For a disease that has been historically overlooked, the availability of these new cutting-edge medicines may represent new hope for people with sickle-cell disease. However, the new drugs might not be accessible to all ~100,000 Americans with the disease. Each treatment must be taken for life and is priced at $100,000 a year, which is double the median family income in the US.

Novartis and Global Blood Therapeutics have been in negotiation with insurance providers about covering the new drugs. Both companies are optimistic that most insurers will pay for the new treatments. The companies argue that without these drugs, the management of sickle-cell disease is expensive. Treating sickle-cell disease complications such as pain, stroke, and organ damage costs about $10,000 a year for children and about $30,000 for adults. Not included in that amount is the economic burden on adults who cannot work due to debilitating disabilities associated with sickle-cell disease and on family members who often wind up as caregivers.

Despite this, some experts and patient advocacy groups question the drug makers’ justification for the treatments’ hefty price tags. Actual development costs and taxpayer support must be considered when setting the price for these treatments. 

More affordable options are available for sickle-cell disease patients. Hydroxyurea, which was approved in 1998 and can reduce the frequency of pain crises and stroke, costs about $1,000 a year. While some patients on public insurance programs have $0 co-pays for Hydroxyurea, only 30% of sickle-cell patients take it. Therefore, insurers may possibly require sickle-cell disease patients to be treated with hydroxyurea before moving on to the more expensive Adakveo or Oxbryta.

Medicaid covers about 50% of sickle-cell disease patients while Medicare covers another 15%. It remains unclear how these programs can afford to pay for all who might need the new drugs. 

(Gina Kolota, New York Times

FDA warns Liveyon about selling unapproved stem-cell products that pose a risk to consumers

The FDA has issued a warning to Liveyon Labs and Liveyon LLC of Yorba Linda, California for making and selling unapproved umbilical cord blood products. The agency also issued a warning for significant deviations from safety practices that create serious risks for patients that receive the stem cell therapy.

In 2018, Liveyon LLC distributed contaminated non-FDA-approved umbilical cord blood products processed by the San Diego-based company, Genetech, Inc. The products were linked to the hospitalization of twelve patients who received the injections or infusions. Liveyon conducted a voluntary recall and began making its own products called Pure and Pure Pro through Liveyon Labs. These products are marketed mainly as a treatment for patients with back, knee, and other joint problems. 

An FDA inspection conducted in May revealed that Liveyon Labs and Liveyon LLC were manufacturing and distributing products that are considered drugs although they did not have the approval to do so. An approved biologics license application is needed to lawfully market a drug and an approved investigational new drug application (IND) is required for a drug to be used in humans during the development stage. No such licenses or INDs exist for Pure and Pure Pro. The inspection also documented that the companies did not meet safety standards, including failing to screen donors’ relevant medical records for communicable disease, inadequate aseptic practices to prevent contamination, and deficient environmental monitoring, such as failing to establish a system for cleaning and disinfection the processing room and equipment. According to the FDA, Liveyon took some corrective actions after the inspection. However, Liveyon has yet to provide “proof of updated policies and procedures” and it did not address its lack of required approvals. 

The FDA requested a response from the companies within 15 working days that details how the issues will be corrected. Failure to correct the problems could lead to seizure, injunction or prosecution. Liveyon said it would cooperate with the FDA. 

(Laurie McGinley, The Washington Post

Written by sciencepolicyforall

December 10, 2019 at 10:57 am

Science Policy Around the Web November 29th, 2019

leave a comment »

By Maria Disotuar, PhD

Source: Pixneo

To Drive Down Insulin Prices, W.H.O. Will Certify Generic Versions

Without insulin, a person with type 1 diabetes cannot survive, and the cost and accessibility to insulin continues to be a problem for individuals suffering from this incurable autoimmune disease. Diabetes mellitus is a chronic metabolic disease characterized by high blood glucose levels. There are two types of diabetes, Type 1 diabetes results from the loss of pancreatic β-cell function, resulting in an inability to produce insulin, a peptide-based hormone. On the other hand, Type 2 diabetes patients are resistant to insulin. Those suffering from Type 1 diabetes require daily insulin therapy to stay alive, and patients with type 2 diabetes require insulin therapy to maintain a healthy lifestyle. Currently, more than 400 million people worldwide have diabetes and this number is expected to increase in the coming years. The main problem being that there are no generic forms of insulin and the price for current insulin analogs has gone from approximately $20 per vial to $250 per vial depending on the type of insulin. This price increase over the past 20 years has made insulin unaffordable for many individuals particularly for younger generations of Americans struggling to pay student loans. For these individuals, seeing the price of insulin jump from $4.34 to $12. 92 per milliliter has meant rationing the lifesaving drug to the bare minimum – a deadly decision for some.

As a response to the growing demand for insulin and skyrocketing prices, the World Health Organization (WHO) has proposed a two year prequalification pilot project, which will allow pharmaceutical companies to produce generic insulin to be evaluated by WHO for efficacy and affordability. These types of pilot projects have been previously deployed to improve the accessibility of life saving drugs for malaria, HIV, and tuberculosis. These efforts have led to an increase in production and market competition leading to reduced costs for individuals.

Currently, the major producers of insulin, Eli Lilly, Novo Nordisk, and Sanofi have welcomed the prequalification program, vowing to be a part of the solution not the problem. According to WHO, companies in several countries, including China and India, have already expressed interest in the pilot project. This shift in insulin production would allow companies producing insulin domestically to enter the global market. As WHO-certified suppliers, these new competitors could dramatically drive down the price of insulin and improve accessibility on a global scale. Despite this positive global outlook, there are still some hurdles to cross for Americans to obtain these generic insulin products. The main one being that the pharmaceutical market is regulated by the FDA and the review process can be expensive for smaller companies. Nonetheless, Americans are fighting back to reduce the cost of insulin and other life savingdrugs, prompting lawmakers, presidential candidates, and the President to prioritize reduced drug prices for Americans. These mounting pressures will hopefully lead to a faster solution for this life or death situation.

(Donald G. McNeil Jr., The New York Times)

Will Microneedle Patches Be the Future of Birth Control?

In 2018, the The Lancet reported that between 2010 and 2014 44% of all pregnancies in the world were unplanned. Despite medical advances in sexual and reproductive health, new contraceptive methods are needed to expand accessibility and improve reliability for women. In the United States, the establishment of the Affordable Care Act (ACA) and health policies such as the Federal Contraceptive Coverage Guarantee, which requires private health plans to include coverage for contraceptives and sexual health services, has improved family planning for women of reproductive age. Despite the social and economic benefits of improved family planning and enhanced accessibility, conservatives continue to challenge these beneficial health policies. Unfavorable changes to these policies could result in major barriers for women to access some of the most effective, yet pricier forms of contraceptives such as intrauterine devices (IUDs) and implants. Studies show these long-acting forms of birth control are up to 20 times more effective in preventing unintended pregnancies than shorter-acting methods such as the pill or ring. Thus, new long-term contraceptives with reduced cost barriers would be essential in reducing unintended pregnancies and enhancing economic benefits on a global scale.

To address this issue, researchers at the Georgia Institute of Technology and University of Michigan in partnership with Family Health International (FHI) – a non profit human development organization, have developed a long-acting contraceptive administered by a patch containing biodegradable microneedles. The patch is placed on the surface of the skin and the microneedles painlessly come into contact withinterstitial fluid resulting in the formation of carbon dioxide bubbles, which allow the microneedles to detach from the patch within 1 minute of application. The needles themselves do not introduce a new contraceptive hormone, rather they provide levonorgestrel (LNG), which is regularly used in IUDs and has been deemed as safe and efficacious. After dissociation from the patch the needles slowly release LNG into the bloodstream. 

Thus far, the pharmacokinetics of the patches has been tested on rats and a placebo version has been tested in humans to test the separation process between the patch and the needles. The in vivo animal studies indicate the patch is able to maintain LNG concentrations at acceptable levels for more than one month and the placebo patch was well tolerated among study participants with only 10% reporting transient pain or redness at the site of patch application. Lastly, the researchers analyzed conceptions and acceptability of this new contraceptive method among American, Indian, and Nigerian women compared to oral contraceptives and monthly contraceptive injections administered by a physician. The results indicate women overwhelmingly preferred the microneedle patch method over the daily pill (90%) or monthly injections (100%). The researchers expect the patch to be simple to mass produce and a low-cost contraceptive option, which will reduce cost barriers and improve accessibility for women. Although the results of the study are promising, additional studies will have to be completed to address some of its limitations. Future studies will have to increase the number of animals used in the study and the number of human participants. Additionally, the release profile for LNG will likely need to be extended beyond 1-month to truly address the need for new long-acting forms of contraceptives. Finally, clinical trials will have to be completed to test the efficacy and general reliability of this method at reducing unintended pregnancies. If the microneedle patch is approved, it would be the first self-administered long-term birth control to enter the market, which could ultimately lead to enhanced accessibility for women with limited access to health care.

(Claire Bugos, Smisothian) 

Science Policy Around the Web September 20th, 2019

leave a comment »

By Allison Cross, PhD

Image from Flickr

Hunt for Cause of Vaping Illness Suggests Multiple Mechanisms of Damage

A vaping-related respiratory illness has affected nearly 500 individuals across 3 dozen states and has been linked to 6 deaths since the first case was reported back in April. Experts, however, are still uncertain about what is causing the nationwide outbreak and even what the condition is exactly.  

report earlier this month from the FDA suggested they may have identified the source of the problem, vitamin E acetate,  a common contaminate in vaping products.  However, more recent information indicates that no single contaminate was identified in all product samples tested from sick individuals. To date, the only thing found in common among the nearly 500 individuals who have fallen ill is that they recently vaped in the US or its territories.  

On September 16th, the U.S. Centers for Disease Control and Prevention activated its Emergency Operations Center (EOC) to help to enhance operations and provide additional support to CDC staff working to identify the cause of the disease.  The CDC advices those concerned about the outbreak to refrain from using e-cigarettes or vaping products.

E-cigarettes and other vaping products have recently been under scrutiny by those concerned about the recent increase in popularity of vaping among adolescents.  Many have been pushing for a ban on flavored e-cigarettes as these products are believed to be deliberately targeting youth.  The recent outbreak has led to renewed calls for a total ban on these and other vaping products.  In response to the outbreak, regulators in New York approved a ban on the sale of flavored e-cigarettes on Tuesday the 17thand Michigan followed suit on Wednesday.   The health and human services secretary, Alex M. Azar II, also announced that the FDA is outlining a plan for removing flavored e-cigarettes and nicotine pods from the market, though finalizing this ban will take several weeks. 

(Emily Willingham, Scientific American)

Trump’s decision to block California vehicle emissions rules could have a wide impact

California has long struggled to reduce smog in its cities and for almost 4 decades, as a part of the federal Clean Air Act, they have been granted special permission by the EPA to set their own air pollution standards.  This may soon change however as President Trump announced that the administration plans to revoke California’s authority to set its own automotive emissions standards. The Trump administration, instead, aims to set a single national standard for automotive emissions. Many are concerned, however, about the more lenient national standard proposed by the Trump administration. 

Although California is only 1 of 49 states, the implications of revoking California’s authority to set its own emission standard are far reaching.  The Clean Air Act currently allows others states to adopt the standards set by California and, as of today, thirteen other states and Washington DC abide by California’s stricter standards. 

The plan currently proposed by the Trump administration aims to freeze fuel-efficiency standards for all vehicles after 2020.  Experts estimate that this new standard would increase average greenhouse gas emissions from new vehicles by 20% in 2025 compared to the level projected under the current rules.  

California leaders have pledged to challenge the decision by the Trump administration in court.  It is likely that other states and environmental groups will join in support of California and it is possible that the lawsuit makes its way all the way to the supreme court. 

 (Jeff Tollefson, Nature

Written by sciencepolicyforall

September 20, 2019 at 5:44 pm

Recent trends and emerging alternatives for combating antibiotic resistance

leave a comment »

By: Soumya Ranganathan, M.S.

Image by Arek Socha from Pixabay 

Antibiotic resistance is an ongoing and rising global threat. While there is a tendency for bacteria and other microbes to develop resistance to antibiotics and antimicrobials slowly over time, the overuse and abuse of antibiotics has accelerated this effect and has led to the current crisis. The new Global Antimicrobial Surveillance System (GLASS), developed by the World Health Organization (WHO), reveals antibiotic resistance is found in 500,000 people with suspected infections across 22 countries. A study supported by the UK government and the Wellcome Trust estimates that antimicrobial resistance (AMR) could lead to an annual death toll of about 10 million by 2050. It is also predicted to have a huge economic impact and could cost 100 trillion USD between 2017 and 2050

Factors underlying the non-targeted use of antibiotics

Prescribing the right antibiotic for an infection takes about a week due to the process of identifying the infectious agent. To avoid the spread of infection, physicians are forced to make a prognosis prior to agent identification, and typically prescribe a broad-spectrum antibiotic. Since the broad-spectrum antibiotics act against a wide range of bacterial strains, their rampant use has led to the emergence of bacterial strains which are resistant to even the most potent antibiotics available. This trend has caused difficulty in treating previously curable hospital acquired infections and other benign infections. Not only is the discovery of new antibiotics is complicated (only one new class of antibiotics has been developed in the past three decades), the development of antibiotics, from discovery to medicine,  also in general takes about 1 to 2 decades. Here we will explore certain alternative strategies scientists all around the world are pursuing in their fight against antibiotic resistance. 

Antibiotic Susceptibility Test  

Reducing the time between a patient becoming ill and receiving treatment is critical for containing and effectively treating the infection. A part of this process that is currently required entails making improvements to the antibiotic susceptibility testing (AST) system, which typically has two steps: (i) Identifying the infectious agent and (ii) Identifying the most effective antibiotic to treat the infection.

Conceptually, new and rapid AST systems have been proposed and developed thanks to advancements in phenotyping methods, digital imaging and genomic approaches. But a plethora of factors act as roadblocks for implementing rigorous and standardized AST systems worldwide. A recently published consensus statement explores the major roadblocks for the development and effective implementation of these technologies while also suggesting ways to move past this stalemate. The major points of the statement are summarized below. 

  • Regulation– Since different regions and countries have their own requirements for marketing and validating a diagnostic method, the onus is on the developers to meet various demands. This also requires harmonization and cooperation among policy makers to formulate and agree on a standard set of rules.
  • Collection and dissemination of information regarding various strains and antibiotics– Antibiograms are a summary of antimicrobial susceptibility rates for selected pathogens to a variety of antimicrobial drugs, provide comprehensive information about the local antibiotic resistance. The challenge here lies in making the data available in real time and in developing a “smart antibiogram”.This is necessary to perform quicker analysis of samples and to reduce the time to treat which eventually translates to increase in lives saved. 
  • Cost involved in developing new, sensitive, and faster diagnostics– Though current diagnostics are cheap they are slow in identifying pathogenic bacteria. The transition to more advanced and sensitive diagnostics has been slow since their developmenttake time and incur more cost. However, this scenario is likely to change soon with the rising levels of antibiotic resistance that are making existing diagnostics obsolete, effectuating more investment in this sector. 

Antivirulence therapy

Small molecules are gaining prominence as an alternative or as adjuvants to antibiotic treatments. Recently, researchers from Case Western University have developed two small molecules F19 and F12 that show promise in the treatment of methicillin resistant Staphylococcus aureus(MRSA) infection in mouse models. The small molecules bind to a Staph. aureustranscription factor called AgrA, deterring it from making toxic proteins and rendering the bacteria harmless. Treatment with F19 on its own resulted in 100% survival rate in a murine MRSA bacteremia/sepsis model while only 30% of untreated mice survived. This kind of antivirulence therapy allows the immune system to clear the pathogens (since the bacteria are essentially harmless) without increasing pressure to develop resistance. When used as an adjuvant with antibiotic, F19 resulted in 10X times lesser bacteria in the mouse bloodstream than treatment with antibiotic alone. This kind of combination therapy can be used on immunocompromised patients. It has also been effective against other bacterial species such as Staph. epidermidis, Strep. pyogenes, and Strep. pneumoniaeand may act as arsenal for a broad variety of gram-positive bacterial infections. Overall the small molecule approach could also bring many of the previously shelved antibiotics back to use as they provide means to improve their efficacy in treating bacterial infections. Another class of engineered proteins called Centyrins show promise to treat Staph. aureusinfection using a similar mechanism, as they bind to the bacterial toxins and prevent them from disrupting the immune system. 

Molecular Boosters

Stanford University chemists (study published in Journal of the American Chemical Society) have developed a booster molecule called r8 which when used in combination with vancomycin (first line antibiotic used for MRSA infections), helps the antibiotic penetrate the biofilm and remain for a long time, enabling it to attack pathogens once they resurge from their dormant stage. This small molecule booster approach could be pursued further to provide existing antibiotics with additional abilities in sieging the pathogens and arresting the spread of infections.

Photobleaching

A recent collaborative effort by scientists from Purdue University and Boston University has resulted in an innovative light-based approach called photobleaching (using light to alter the activity of molecules) to treat certain bacterial infections. Photobleaching of MRSA using low-level blue (460nm) light has been found to lead to the breakdown of STX, an antioxidant (pigment) found in the membrane of bacteria. Since STX protects the bacteria against neutrophils (a class of white blood cells involved in body’s immune mechanism), prior attempts have been made using medication to eliminate the STX but those efforts have been futile. Photolysis of STX leads to transient increase in the permeability of bacterial membrane, rendering them more susceptible to even mild antiseptics like hydrogen peroxide and other reactive oxygen species. Since pigmentation is a “hallmark of multiple pathogenic microbes” this technology could be extended for use in other microbes to tackle resistance. In addition to advantages such as ease of use and development, photobleaching could also be used with minimal or no adverse side effects. 

Antisense Therapy

One of the consequences of the non-targeted use of antibiotics to treat infections has been the occurrence of C.difficileinfection in the colon. This condition is due to the elimination of useful bacteria along with the harmful bacteria in the gut. To tackle this infection, Dr. Stewart’s team from the University of Arizona has developed an antisense therapy which act by silencing genes responsible for the survival of pathogenic bacteria while sparing other useful bacteria in the gut. This strategy involves using molecules with two components – an antisense oligonucleotide moiety that targets the genetic material in C.diffand a carrier compound to transport the genetic material into the bacterium. Though this treatment approach shows potential in providing a targeted, less-toxic, nimble and cost-effective alternative against existing and evolving pathogens, clinical trials must be undertaken to see its effects in practice.

Future perspectives

In addition to the aforementioned strategies, the scientific community is pursuing immune modulation therapy, host-directed therapy, and probiotics to deal with the current AMR crisis. The problem with developing new antibiotics is that microbes will eventually develop resistance to them. Though time will reveal the approaches that are truly effective in evading antibiotic resistance, the looming threat must be dealt with prudently. A holistic approach to restrict and channel the targeted use of antibiotics while pursuing alternative therapies must be adopted by the clinicians, researchers, companies, global health experts, public and policy makers to curb the resistance emergency.

Have an interesting science policy link? Share it in the comments!

Written by sciencepolicyforall

April 26, 2019 at 4:35 pm

Posted in Essays

Tagged with , , ,

The need for regulation of artificial intelligence

leave a comment »

By: Jayasai Rajagopal, Ph.D.


Source: Wikimedia

The development and improvement of artificial intelligence (AI) portends change and revolution in many fields. A quick glance at the Wikipedia article on applications of artificial intelligence highlights the breadth of fields that have already been affected by these developments: healthcare, marketing, finance, music and may others. As these algorithms increase their complexity and grow in their ability to solve more diverse problems, the need to define rules by which AI is developed becomes more and more important.

            Before explaining the potential pitfalls of AI, a brief explanation of the technology is required. Attempting to define artificial intelligence begs the question of what is meant by intelligence in the first place. Poole, Mackworth and Goebel clarify that for an agent to be considered intelligent, they must adapt to their surrounding circumstances, learn from changes in those circumstances, and apply that experience in pursuit of a particular goal. A machine that is able to adapt to changing parameters, adjust its programming, and continue to pursue a specified directive is an example of artificial intelligence. While such simulacra are found throughout science fiction, dating back to Mary Shelly’s Frankenstein, they are a more recent phenomenon in the real world. 

            Development of AI technology has taken off within the last few decades, as computer processing power has increased. Computers began successfully competing against humans in chess as early as 1997 with DeepBlue’s victory over Garry Kasparov. In recent years, computers have started to earn victories in even more complex games such as Go and even video games such as Dota 2. Artificial intelligence programs have become common place for many companies which use them to monitor their products and improve the performance of their services. A report in 2017 found that one in five companies employed some form of AI in their workings. Such applications are only going to become more commonplace in the future.

In the healthcare field, the prominence of AI is readily visible. A report by BGV predicted a total of $6.6 billion invested into AI within healthcare by the year of 2021. Accenture found that this could lead to saving of up to $150 billion by 2026. With the recent push towards personalized and precision medicine, AI can greatly improve the treatment and quality of care. 

However, there are pitfalls associated with AI. At the forefront, AI poses a potential risk for abuse by bad actors. Companies and websites are frequently reported in the news for being hacked and losing customer’s personal information. The 2017 WannaCry attack crippled the UK’s healthcare system, as regular operations at many institutions were halted due to their compromised data infrastructures. While cyberdefenses will evolve with the use of AI, there is a legitimate fear that bad actors could just as easily utilize AI in their attacks. Regulation of use and development of AI can limit the number of such actors that could access those technologies.

Another concern with AI is the privacy question associated with the amount of data required. Neural networks, which seek to imitate the neurological processing of the human brain, require large amounts of data to reliably generate their conclusions. Such large amounts of data need to be curated carefully to make sure that identifying information that could compromise the privacy of citizens is not easily divulged. Additionally, data mining and other AI algorithms could information that individuals may not want revealed. In 2012, a coupon suggestion algorithm used by Target was able to discern the probability that some of their shoppers were pregnant. This proved problematic for one teenager, whose father wanted to know why Target was sending his daughter coupons for maternity clothes and baby cribs. As with the cyberwarfare concern, regulation is a critical component in protecting the privacy of citizens.

Finally, in some fields including healthcare, there is an ever present concern that artificial intelligence may replace some operations entirely. For example, in radiology, there is a fear that improvements in image analysis and computer-aided diagnosis by the use of neural networks could replace clinicians. For the healthcare field in particular, this raises several important ethical questions. What if the diagnosis of an algorithm disagrees with a clinician? As the knowledge an algorithm has is limited by the information it is exposed to, how will it react when a unique case is presented? From this perspective, regulation of AI is important not only to address practical concerns, but also pre-emptively answer ethical questions.

While regulation as strict as the Asmiov’s Three Laws may not be required, a more uniform set of rules governing AI is required. At the international level, there is much debate among the members of the United Nations as to how to address the issue of cyber security. Other organizations, such as the European Union, have made more progress. A document recently released by the EU highlights some ethical guidelines which may serve as the foundation for future regulations. At the domestic level, there has been a push from scientists and leaders in the field towards harnessing the development of artificial intelligence for the good of all. In particular, significant headway has been made in the regulation of self-driving cars. Laws passed in California restrict how the cars can be tested and by 2014, four states already had legislation applying to these kinds of cars. 

Moreover, the FDA recently released a statement expressing their approach to the regulation of artificial intelligence in the context of medical devices. At the time of this writing, there is a discussion paper that is open for commentary describing the proposed approach that the FDA may take. They note that the conventional methods of acquiring pre-market clearance for devices may not apply to artificial intelligence. The newly proposed framework adapts existing practices to the context of software improvements.  

Regulation must also be handled with care. Over-limitation of the use and research in artificial intelligence could lead to stifling of development. Laws must be made with knowledge of the potential benefits of new technological advancements could cause. As noted by Gurkaynak, Yilmaz, and Haksever, lawmakers must strike a balance between preserving the interests of humanity and the benefits of technological improvement. Indeed, artificial intelligence poses many challenges for legal scholars.

In the end, artificial intelligence is an exciting technological development that can change the way we go about our daily business. With proper regulation, legislation, and research focus, this technology can be harnessed in a way that benefits the human experience while preserving development and the security of persons.

Have an interesting science policy link? Share it in the comments!

Written by sciencepolicyforall

April 18, 2019 at 2:25 pm