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Posts Tagged ‘clinical trials

Science Policy Around the Web April 30th, 2020

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By Ken Farabaugh, PhD

Image by MiroslavaChrienova from Pixabay

We’re repeating one of the worst mistakes of the Ebola outbreak in the hunt for a coronavirus cure

In 2014, Dr. Kent Brantly was the first American infected with Ebola. He was also the first American to recover from Ebola, after treatment with the experimental drug ZMapp. He was the face of “The Ebola Fighters,” Time Magazine’s person of the year. Four years and a second Ebola outbreak later, controlled drug trials demonstrated that ZMapp was not an effective treatment for the disease. A major issue that delayed this finding was that many prominent researchers, including advisors of the WHO and Doctors Without Borders, were against trials in which some patients would not be given the standard of care or the “secret serum” ZMapp. By the time scientists around the world had come up with a strategy to plan clinical trials to treat Ebola, the pandemic had waned and there were fewer and fewer patients to enroll in the studies. 

Although there are over 200 ongoing clinical trials around the world for drugs to treat COVID-19 (remdesivir, hydroxychloroquine, etc), few studies are being conducted with enough scientific rigor. Although randomized, well-controlled trials can take months to set up properly, it is still the best way to obtain high-quality data. Studies that do not follow these guidelines often produce low-quality data that cannot be replicated or conflicts with other findings. Only about 20% of current coronavirus drug trials (according to Ann Meeker-O’Connell, VP of Vertex Pharmaceuticals) have enough patients to statistically power the study, have a control group being administered a placebo, and are blinded to both patients and doctors. 

Despite possible problems in study design, some benefits from the numerous drug trials currently being undertaken include increased collaboration between government agencies, non-profits, and big pharma companies. Databases are also being constructed with health records and demographic information of all COVID-19 patients. The challenge in the coming years will be sifting through all the data from the drug trials being performed, both good and bad, to determine if the drugs actually worked.

(Andrew Dunn, Business Insider)

The world wants answers on Gilead’s Covid-19 drug. Experts worry next studies may increase uncertainty

The drug company Gilead has sponsored two trials in the US to test the effectiveness of their antiviral drug remdesivir against COVID-19. In the first trial, a summary of which was released April 29th, the drug alone was given to patients for 5 or 10 days to evaluate safety and efficacy; no difference was observed in the treated groups, although the efficacy of the drug was not measured as there was no control group treated with a placebo. Gilead has suggested that the benefits of remdesivir are expected to only modestly affect patient recovery, rather than a silver bullet cure.

Results from a separate study in China leaked by the WHO last week and published April 29th suggested that remdesivir had no statistically beneficial effect on survival of severely ill patients compared to a control group, though there was potential reduction in time to clinical improvement. However, the study also reported that 12% of patients on remdesivir halted treatment due to adverse effects compared to 5% of patients on the placebo.

The most clarity will come from a NIAID-run trial, data from which is not expected until late May. Preliminary data released April 29th suggests that remdesivir led to a 31% decrease in recovery time (11 days from 15 days) and a 8% mortality rate (survival benefit from the placebo group at 11.6% mortality). Although this data is promising, it is important to note that these results are preliminary, that this treatment is not a replacement for a vaccine, and that Gilead has already mentioned production issues in rationalizing the design of their own studies.

(Matthew Herper and Adam Feuerstein, STAT)

Written by sciencepolicyforall

April 30, 2020 at 4:48 pm

Science Policy Around the Web February 20th, 2020

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By Somayeh Hooshmand, PhD

Image by skeeze from Pixabay 

Researchers Identify States Where Improved Sun Protection Could Prevent the Most Melanomas

Rates of new cancer diagnoses continue to increase in the US, and skin cancer is one of the most common. Although many skin cancer cases can be prevented, it greatly affects quality of life, making it a major public health concern. According to a recent study, 91% of all melanomas in the US are caused by too much exposure to ultraviolet (UV) radiation from the sun. However, the rates vary among populations, and are as high as 94% among non-Hispanic whites. This study focused on the non-Hispanic white population at the state level that exhibit higher levels of melanoma and suggested sun protection measures across the states.

While incidence rates for melanoma as a result of exposure to the UV radiation was noticeably high in all states, the District of Columbia had the lowest proportion of melanoma among non‐Hispanic whites —87.6% of all cases and Hawaii had the highest, with 97.3%  of all cases. 

How to protect yourself from UV radiation:

The risk of skin damage increases when you stay in the sun for a long time, especially with a high UV Index and without sufficient sun protection. Dr. Farhad Islami, MD, PhD, said that “The amount of UV exposure you get depends on both the strength of the sun’s rays—measured by the UV Index—and the length of the time your skin is exposed to it”. He said “You can’t change the UV Index, but you can change how long you’re outside and how you protect your skin”. 

You should use sunscreen with a sun protection factor (SPF) of 15 or higher and limit the amount of time you’re in the sun, avoid peak sunlight, wear sunglasses and try to reduce indoor tanning. The authors hope that state- and community-level cancer control programs will result in school-based programs and indoor tanning regulations based on this research findings.

(Amy Maxmem, Nature)

‘Ghost’ DNA In West Africans Complicates Story of Human Origins

The genetic history of people in present-day West Africa indicates an earlier episode of breeding between different groups, leading to introgression of genetic material into modern humans. 

The recent research in human genetics by Sankararaman et al. found “ghost DNA” by analyzing the genomes of 405 West Africans, and suggests that about 50,000 years ago, ancient human procreated with another group of ancient humans or unknown ancestors that scientists so far did not know existed. The understanding so far has been that Homo sapiens, our own species lived alongside other groups that split off at different times from the same genetic family tree. There exists abundant evidence from other parts of the world that early humans had sex with other groups, like Neanderthals (found in people of European and Asian descent today) and Denisovans (found in people from Oceania). They state that the found unusual DNA came from a yet-to-be-discovered group, as it isn’t associated with either Neanderthals or Denisovans. The lack of knowledge about this group led the researchers to term it ‘ghost’ DNA. They think that this occurred due to interbreeding (single event or over an extended period of time) around the same time when Neanderthals were breeding with modern humans elsewhere in the world.

Their findings appear in the journal Science Advances, but there are still many questions about  ‘Ghost’ DNA that remain unanswered. As Sankararaman says, “Are they just randomly floating in our genomes? Do they have any kind of adaptive benefits? Do they have deleterious consequences? Those are all questions which would be fantastic to start thinking about.”

(Merrit Kennedy, NPR)

Written by sciencepolicyforall

February 20, 2020 at 4:28 pm

Science Policy Around the Web February 18th, 2020

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By Silvia Preite, PhD

Image by Konstantin Kolosov from Pixabay 

How science is fighting the new Coronavirus disease 2019 (COVID-19)

The increase in new infections of the novel coronavirus, recently named SARS-CoV-2, COVID-19), is being tightly monitored by the WHO (World Health Organization). Currently there are 71,429 confirmed world-wide cases, and 1772 deaths in China. Scientists around the world are making extensive efforts to fight COVID-19 in multiple ways: 1) utilizing epidemiology to understand how and why the virus is spreading; 2) studying the genetic composition of the virus to learn how it works, survives and spreads across species; 3) conducing biomedical research to find and test effective therapeutics. The development of novel drugs is generally a slow process, usually taking several years to be completed. Therefore, with the urgency of the current epidemic, specific vaccine development and identification and production of viral neutralizing antibodies do not seem useful immediate solutions. 

The scientific community is mainly directing its attention toward the exploration of already developed drugs, such as antivirals, stem cells, and Chinese traditional medicines. Examples of these drugs are an HIV-drug cocktail (lopinavir and ritonavir) and an experimental antiviral called remdesivir. Both options have shown initial promise in animal models infected by related strains of coronaviruses. Other tested treatment includes a malaria drug (chloroquine) and steroids, respectively aimed at killing the virus and reducing inflammation.

Overall, China is currently launching more than 80 clinical trials to test treatments for this coronavirus. To ensure high quality and public trust in the outcomes of these trials, the WHO is working closely with Chinese scientists and authorities to set standards to design, execute, and analyze these studies properly. 

Failing to control the infection could result in the virus becoming endemic, like seasonal influenza infection. Sharing of research results at global levels and adequately designed clinical trials are two essential elements that the medical and scientific community is currently adopting to properly fight the infection. Meanwhile, basic and translational research all over the world is moving forward to search for new drugs that would be useful in the future to combat multiple coronaviruses, including the ones that we haven’t faced yet. 

Written by sciencepolicyforall

February 18, 2020 at 3:57 pm

Science Policy Around the Web February 4th, 2020

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By Maria Disotuar PhD

Source: Flickr

Embryo Research To Reduce Need For In Vitro Fertilization Raises Ethical Concerns 

The year 2019 ended with the publishing of a controversial and potentially unethical study completed in Mexico in which  81 women were paid approximately ~$1400 to be injected with synthetic hormones, artificially inseminated, and have their embryos flushed out of their bodies (a procedure known as uterine lavage) to test them genetically and analyze their morphology. A subset of 20 out of the 81 women followed the procedure by a cycle of in vitro fertilization (IVF)  to compare the embryos produced in the lab versus the embryos produced via uterine lavage. In the study, scientists were able to recover 42% of the flushed embryos and 70% of these embryos were of good quality. The scientists noted the embryos recovered via this method had better morphology than those recovered via IVF and the chromosomal variations were similar between the two methods. 

Currently, IVF is the most common type of assisted reproductive technology(ART) but it can cost over $20,000 per cycle, and according to the Society for Assisted Technology (SART) the rate of single births per IVF cycle can vary from 4% to 41% depending on a woman’s age. Dr. Santiago Munne, the principal investigator of the study, hopes the new method could one day replace IVF. He hopes this new alternative, once perfected, will increase birth rates since the procedure is completed in vivo, lead to a reduction in chromosomal abnormalities, reduce costs, and provide an alternative method for couples struggling to conceive.

Yet, some bioethicists and scientists across the globe have described the study as troublesome, unethical, and dangerous. They worry the women were used as “petri dishes” for a procedure normally reserved for individuals experiencing infertility problems. More worrisome is that some of the women underwent chemical or surgical abortions after some of the embryos were not successfully removed during the procedure. Despite these concerns, Dr. Munne notes the study was approved by the Ministry of Health of the State of Nayarit, in Mexico, and the Western Institutional Review Board in the United States. Additionally, some scientists acknowledge the study was well done and could have a positive impact on reproductive research and may help couples conceive at a lower cost in the future. Finally, the study has helped couples struggling with infertility as some embryos have been used to produce healthy babies. The remaining embryos have been frozen for future use by other couples. 

Rob Stein, NPR 

FDA and NIH let clinical trial sponsors keep results secret and break the law

The federal government mandates research institutions report all clinical trial results so that doctors and patients can make informed decisions about disease treatment plans. In January 2018, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) established a “final rule” to clarify the expectations, rules, and penalties for not disclosing the results from clinical trials. Based on this mandate clinical trial sponsors must submit data and results within 1 year after the completion of a clinical trial.  Now, two years after the establishment of the mandate, a Science investigation shows that clinical trial sponsors are not obeying the law and very little is being done by the federal government to address the issue. 

The investigation looked at more than 4700 trials registered on and found that while reporting rates for some pharmaceutical companies and universities had increased since the establishment of the rule, 31.6% of sponsors had not reported their results to the website and 23.7% had reported their results past the 1 year time frame. In the months leading to the establishment of the rule the FDA and the NIH promised stiff penalties for violators – including fines of up to $12,000 a day and cutting grant funds for not reporting the results of the trials on time. This was promised as a measure to enforce the mandate and maintain compliance within the research community. Yet, the findings of this investigation clearly show that neither the NIH nor the FDA are fulfilling their promises, and sponsors are not being penalized for withholding vital information from the public. 

(Charles Piller, Science) 

Written by sciencepolicyforall

February 4, 2020 at 9:16 am

Expedited Drug Approvals: When Speeding Saves Lives

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By: Maria Disotaur, PhD


Changes in laws and regulations have accelerated the drug approval process for rare and fatal diseases. Yet, some experts worry the process is now moving too fast, while others argue that slowing down the process could cost patients their lives. 

The first case of acquired immunodeficiency syndrome (AIDS) in the United States was reported in 1981. Ten years later, more than 250,000 Americans were living with the disease or had died from the epidemic. During this time, activist groups believed the drug approval process was unacceptably slow and possibly leading to the deaths of thousands of Americans. They demanded drugs be proven safe and effective at a faster rate because prior to 1992, the Food and Drug Administration’s (FDA) drug approval process could take two and a half to 8 years due to poor staffing and lack of resources within the agency. Protests at the FDA headquarters, led to the establishment of streamlined policies and regulations designed to speed the approval process for life-saving drugs for serious and often fatal diseases. 

In 1992, a series of complex regulations and processes were established to place life-saving drugs in the hands of patients as expeditiously as possible. Beginning with the Prescription Drug User Fee Act (PDUFA), the agency could charge pharmaceutical companies a $200,000 reviewer fee for a new drug approval application (NDA). This new policy increased agency funds, personnel, and reduced the amount of time to approve a new drug to approximately eighteen months. To further expedite the process the agency introduced accelerated approval and priority review. The former allowed the FDA to use a surrogate endpoint to approve a new drug for a serious medical condition with an unmet medical need. Priority review, required the FDA to review a drug within six months compared to the standard ten months, if the drug showed evidence of significant improvement in treatment, diagnosis, or prevention. These were followed by fast track designation in 1998 and breakthrough therapy designation in 2012, which were designed to expedite the development and review of life-saving drugs that, respectively, fulfilled an unmet need or were better than current market drugs. 

Since their introduction, these regulations have garnered two opposing groups: those that think the drug approval process is moving too fast and those that think it is not moving fast enough. Pharmaceutical companies, health professionals, and patient advocacy groups have argued that millions of Americans are suffering from rare and orphan diseases that require new or enhanced therapies. On the other hand, experts argue that the pathway to expedite drug approvals does not change the fundamental principles of testing the efficacy of a new drug through extensive preclinical research and clinical trials. A recent study published in the Journal of the American Medical Association (JAMA) points to some of the downfalls associated with the FDA’s accelerated approval process. The study looked at 93 cancer drugs approved by the FDA from 1992 to 2017 through the accelerated approval pathway and analyzed the results of confirmatory trials, which are phase 4 post-marketing trials required by the FDA to confirm the clinical benefit of a drug. The study showed that out of the 93 cancer drugs approved only 19 drugs had confirmatory trials that reported an improvement in the overall survival of patients. The study authors concluded that “it is important to recognize the clinical and scientific trade-offs of this approach” particularly since “the clinical community will have less information about the risks and benefits of drugs approved via the accelerated approval program” until confirmatory trials are completed to analyze the clinical benefit and survival for patients. Furthermore, others like Dr. Michael Carome, a physician and a director at the consumer advocacy group Public Citizen, have raised concerns about the medical value and cost of drugs that have limited scientific data. Particularly, the burden placed on families and patients for drugs that in some instances, or in the case of the article published by JAMA, 80% of instances, never prove effective and do not improve patient survival. This was the case for Eli Lilly’s drug Lartruvo, as reported by the Wall Street Journal last summer. In 2016, Lartruvo became the first drug approved by the FDA for soft-tissue sarcoma since the 1970’s. The drug was approved via the accelerated approval pathway after Elli Lilly completed a study with 133 patients showing that Lartruvo with chemotherapy treatment extended the median patient survival by 11.8 months compared to patients using chemotherapy alone. By April 2019, Elli Lilly announced it was removing Lartruvo from the market because in Phase 3 clinical trials, it did not show improvement in patient survival. The removal of Lartruvo from the market left patients dismayed and questioning the long-term effects of the treatment. Prior to Lartruvo’s approval, Dr. James Liebman, an oncologist from Beverly Hospital, and Dr. Hussein Tawbi, an associate professor at MD Anderson Cancer Center expressed concerns about the limited sample size and confounding results for Lartruvo and recommended the FDA delay the approval until other trials were conducted. At the time, the FDA acknowledged their concerns but also acknowledged that the treatments for advanced sarcoma were limited and that the drug could have a clinical benefit on the market. 

These critical decisions are becoming more routine as the FDA tries to meet the demands of doctors, patients, and lawmakers to approve drugs for fatal diseases at a faster rate. In 2009, only 10 drugs were approved through an expedited pathway – either fast-track, priority review, accelerated approval, or breakthrough therapy. Last year, this number increased to 43 drugs out of the 59 novel drugs approved. This jump can be partially accredited to the 21st Century Cures Act, which is designed to expedite the development of new devices and drugs and in some instances, the act allows the FDA to review anecdotal evidence such as patients’ perspectives when reviewing a new drug. Additionally, the increase can be attributed to new biological and diagnostic tools. For example, the use of flow cytometry and next generation DNA sequencing, which allows scientists to detect one cancer cell in a million healthy cells as reported by Scientific American last month. This new measure is called minimal residual disease (MRD) and scientists hope it can be used to accelerate clinical trials and the development of novel drugs. Currently, studies looking at B-cell acute lymphoblastic leukemia indicate MRD-positive patients are more likely to relapse and patients with more than 1 residual cancer cell in 10,000 cells lived approximately six months without relapse, while those that had less than 1 residual cancer cell in 10,000 lived an average of two years without relapse. Scientists hope this method can be used as a future surrogate endpoint and some patient advocacy groups believe that for some cancers like multiple myeloma there is enough evidence to use the method today. A study published in JAMA showed that multiple myeloma patients who were MRD-negative had reduced remission rates and had a 50% longer survival outcomes than those who were MRD-positive. The predictors of MRD indicate that for certain cancers scientists could use this as an alternative surrogate endpoint – it could speed up clinical trials compared to those that look at tumor shrinkage and overall survival. These types of new tools and diagnostics have been prompting patients and doctors to demand faster drug approvals, particularly for rare and life-threatening diseases. Furthermore, they have also compelled FDA officials and leaders like Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, to acknowledge that new scientific tools and advancements will continue to speed up the drug approval process. Concurrently, the agency understands the demands of patients living with life-threatening illnesses and is preparing to enhance its best practices. In a recent-press release, the FDA announced it would begin the “reorganization of the office of new drugs with corresponding changes to the office of translational sciences and the office of pharmaceutical quality.” This strategic move aims to “create offices that align interrelated disease areas and divisions with clearer and more focused areas of expertise”. The goal is to enhance efficiency and provide FDA scientists with a better understanding of diseases that may require future FDA drug approval. These types of changes within the FDA infrastructure, along with biological advancements, will continue to impact the speed at which the FDA approves new drugs. Some individuals will argue that accelerating the process is reckless and a danger to vulnerable patients; however, for some of these patients accelerating the process can be the difference between life and death. For these patients, the question of expediting access to new treatments is not “Are we moving too fast?” it is “Can we afford not to?”

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Written by sciencepolicyforall

January 17, 2020 at 6:48 pm

Science Policy Around the Web November 15th, 2019

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By Mohor Sengupta PhD

Image by David Mark from Pixabay

Rollout of Johnson & Johnson Ebola vaccine begins in Congo

To the African countries reeling with the second deadliest Ebola outbreak in history, two back-to-back launches of new vaccines may be a beacon of hope. On Tuesday this week, Merck’s vaccine Ervebo was pre-qualified by the WHO, meaning that it was declared safe for use. This occurred merely 48 hours after the European Commission granted conditional marketing authorization for the vaccine. The speed of this decision-making sheds light on the gravity of the situation at hand. 

The current outbreak in the Democratic Republic of Congo has killed more than 2,200 people. The previous Ebola outbreak, and the deadliest in living memory, rocked West Africa in 2013-16, claiming 11,300 lives. 

In addition to Ervebo, a new vaccine produced by Johnson & Johnson was approved yesterday. It passed several clinical trials, however it will now be tested for the first time in a real world setting in the village of Goma, on the Rwandan border with DRC. It will be administered to 50,000 people. 

The new vaccine by Johnson & Johnson is aimed at complementing Ervebo. While the later requires a single shot, the Johnson & Johnson vaccine will require two shots spaced at 8 weeks. Ervebo is being used as “ring-vaccination”, a strategy in which close contacts of Ebola-infected individuals will be vaccinated.  

(Reporting by Fiston Mahamba; Writing by Hereward Holland; Editing by Anna Pujol-Mazzini and Mark PotterReuters)

Written by sciencepolicyforall

November 15, 2019 at 4:35 pm

Science Policy Around the Web September 30th, 2019

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By Allison Dennis B.S.

Image by Gerd Altmann from Pixabay 

23andMe, moving beyond consumer DNA tests, is building a clinical trial recruitment business

Clinical trials are often criticized for poor patient recruitment that inadequately represents patients from minorities, e.g., women of reproductive age, racial minorities, underserved patient populations and people with rare genetic diseases. To fight this, 23andMe feels that its vast database of patients comfortable enough to trade their genetic information and a small bit of spit to learn more about their genetic predisposition to disease and heritage could be a much-needed recruiting tool for those enrolling patients in clinical trials, and one they would be willing to pay for. 

23andMe can mine the database of their 8 million potential research participants to identify which customers fit the needed demographics and genetic profiles relevant for studying a particular drug. For example, 23andMe found about 7,500 carriers of a rare mutation in the gene LRRK2, a potential target being pursued by GlaxoSmithKline to prevent the progression of Parkinson’s disease. In patient populations, this mutation is only found in one in a thousand people, meaning it would take years to identify enough participants to enroll in a trial. With enough potential participants to choose from trial managers are hoping to to recruit local patients, allowing them to overcome the costs of paying for patient travel and ease the stress patients experience by spending extended time away from home.

To augment the diversity of their database, 23andMe has launched programs to provide free genetic analysis to people whose four grandparents were born in the same country. The Global Genetics Project focuses on underrepresented countries like Mali, Tajikistan, and Paraguay, while the African Genetics Project focuses on the ethnic and tribal groups of countries such as Cameroon, Ghana, Libera, and Senegal. By starting with the genomes of people with clearly known ancestry to better define the genetic differences common to them, 23andMe is hoping it will be able to improve its unravelling of more complicated genetic lineages. A greater diversity of enrollees is sure to appeal to clinical trial recruiters, who are trying to meet FDA guidelines designed to enhance the diversity of clinical trial populations.

It remains to be seen how receptive 23andMe customers will be to being targeted for participation in clinical trials. Many of the 8 million may not have fully realized that consenting to genetic research would potentially extend to drug companies paying for their data. However, for many people, the possibility of playing a role in the discovery of cures for genetic diseases may outweigh privacy concerns and any initial discomfort from being singled-out. 

(Rebecca Robbins, STAT News)

NIH reveals its formula for tracking foreign influences

NIH’s extramural research program is struggling to find the balance between curbing inappropriate information sharing, fostering the international collaboration recognized as necessary for the global pursuit of science and maintaining some level of ease in the grant application process. The grants that are distributed by NIH are won following review by a panel of experts, composed of about 27,000 reviewers recruited to serve on committees by NIH each year. It is believed that some reviewers have violated NIH policy by sharing the confidential contents of grant applications with international colleagues. The data and research approaches described in grant applications is proprietary and often has the potential to result in patents in addition to publications. 

A more complicated scheme concerning officials involves international researchers setting up labs in parallel, one in the US to win grant money, and one in a foreign country where the grant winner wishes to benefit from any emerging intellectual properties stemming from the funded research. Such an arrangement allows US funded discoveries to be transferred to another country without any oversight from the US government. 

It is difficult to clearly spot scientists unfairly leveraging their role in NIH grant giving activities. While grant reviewers are not supposed to share any parts of the application, it is common for researchers to share grants with trainees in their lab, sometimes seeking relief from the burden of review by having junior researchers take the first look, other times viewing it as a needed opportunity for future grant-seekers to become familiar with the process. Grant applicants routinely have joint appointments with international institutions. This is acceptable if clearly disclosed when they seek funding from NIH. 

In the past the issue has been treated as a regulatory hot potato, NIH requires grant seeking institutions certify the grantee listed on the application, institutions rely on the assumption that foreign scientists would be denied visas by the US Department of state if they were thought to have improper ties to their home countries. Of course, citizens that are US citizens are at risk of behaving improperly as well. NIH is taking the next sixth months to develop a risk-based approach to flag potential conflicts with reviewers. As a first step they are considering moving grant reviews to a read-only online portal to prevent any untracked distribution of downloaded applications. 

 (Jeffrey Mervis, Science)

Written by sciencepolicyforall

October 1, 2019 at 11:32 am