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Archive for the ‘Law and Medicine Conflicts’ Category


US Responses to Coronavirus Outbreak Expose Many Flaws in Our Medical System

Curator: Stephen J. Williams, Ph.D.

The  coronavirus pandemic has affected almost every country in every continent however, after months of the novel advent of novel COVID-19 cases, it has become apparent that the varied clinical responses in this epidemic (and outcomes) have laid bare some of the strong and weak aspects in, both our worldwide capabilities to respond to infectious outbreaks in a global coordinated response and in individual countries’ response to their localized epidemics.

 

Some nations, like Israel, have initiated a coordinated government-private-health system wide action plan and have shown success in limiting both new cases and COVID-19 related deaths.  After the initial Wuhan China outbreak, China closed borders and the government initiated health related procedures including the building of new hospitals. As of writing today, Wuhan has experienced no new cases of COVID-19 for two straight days.

 

However, the response in the US has been perplexing and has highlighted some glaring problems that have been augmented in this crisis, in the view of this writer.    In my view, which has been formulated after social discussion with members in the field ,these issues can be centered on three major areas of deficiencies in the United States that have hindered a rapid and successful response to this current crisis and potential future crises of this nature.

 

 

  1. The mistrust or misunderstanding of science in the United States
  2. Lack of communication and connection between patients and those involved in the healthcare industry
  3. Socio-geographical inequalities within the US healthcare system

 

1. The mistrust or misunderstanding of science in the United States

 

For the past decade, anyone involved in science, whether directly as active bench scientists, regulatory scientists, scientists involved in science and health policy, or environmental scientists can attest to the constant pressure to not only defend their profession but also to defend the entire scientific process and community from an onslaught of misinformation, mistrust and anxiety toward the field of science.  This can be seen in many of the editorials in scientific publications including the journal Science and Scientific American (as shown below)

 

Stepping Away from Microscopes, Thousands Protest War on Science

Boston rally coincides with annual American Association for the Advancement of Science (AAAS) conference and is a precursor to the March for Science in Washington, D.C.

byLauren McCauley, staff writer

Responding to the troubling suppression of science under the Trump administration, thousands of scientists, allies, and frontline communities are holding a rally in Boston’s Copley Square on Sunday.

#standupforscience Tweets

 

“Science serves the common good,” reads the call to action. “It protects the health of our communities, the safety of our families, the education of our children, the foundation of our economy and jobs, and the future we all want to live in and preserve for coming generations.”

It continues: 

But it’s under attack—both science itself, and the unalienable rights that scientists help uphold and protect. 

From the muzzling of scientists and government agencies, to the immigration ban, the deletion of scientific data, and the de-funding of public science, the erosion of our institutions of science is a dangerous direction for our country. Real people and communities bear the brunt of these actions.

The rally was planned to coincide with the annual American Association for the Advancement of Science (AAAS) conference, which draws thousands of science professionals, and is a precursor to the March for Science in Washington, D.C. and in cities around the world on April 22.

 

Source: https://www.commondreams.org/news/2017/02/19/stepping-away-microscopes-thousands-protest-war-science

https://images.app.goo.gl/UXizCsX4g5wZjVtz9

 

https://www.washingtonpost.com/video/c/embed/85438fbe-278d-11e7-928e-3624539060e8

 

 

The American Association for Cancer Research (AACR) also had marches for public awareness of science and meaningful science policy at their annual conference in Washington, D.C. in 2017 (see here for free recordings of some talks including Joe Biden’s announcement of the Cancer Moonshot program) and also sponsored events such as the Rally for Medical Research.  This patient advocacy effort is led by the cancer clinicians and scientific researchers to rally public support for cancer research for the benefit of those affected by the disease.

Source: https://leadingdiscoveries.aacr.org/cancer-patients-front-and-center/

 

 

     However, some feel that scientists are being too sensitive and that science policy and science-based decision making may not be under that much of a threat in this country. Yet even as some people think that there is no actual war on science and on scientists they realize that the public is not engaged in science and may not be sympathetic to the scientific process or trust scientists’ opinions. 

 

   

From Scientific American: Is There Really a War on Science? People who oppose vaccines, GMOs and climate change evidence may be more anxious than antagonistic

 

Certainly, opponents of genetically modified crops, vaccinations that are required for children and climate science have become louder and more organized in recent times. But opponents typically live in separate camps and protest single issues, not science as a whole, said science historian and philosopher Roberta Millstein of the University of California, Davis. She spoke at a standing-room only panel session at the American Association for the Advancement of Science’s annual meeting, held in Washington, D.C. All the speakers advocated for a scientifically informed citizenry and public policy, and most discouraged broadly applied battle-themed rhetoric.

 

Source: https://www.scientificamerican.com/article/is-there-really-a-war-on-science/

 

      In general, it appears to be a major misunderstanding by the public of the scientific process, and principles of scientific discovery, which may be the fault of miscommunication by scientists or agendas which have the goals of subverting or misdirecting public policy decisions from scientific discourse and investigation.

 

This can lead to an information vacuum, which, in this age of rapid social media communication,

can quickly perpetuate misinformation.

 

This perpetuation of misinformation was very evident in a Twitter feed discussion with Dr. Eric Topol, M.D. (cardiologist and Founder and Director of the Scripps Research Translational  Institute) on the US President’s tweet on the use of the antimalarial drug hydroxychloroquine based on President Trump referencing a single study in the International Journal of Antimicrobial Agents.  The Twitter thread became a sort of “scientific journal club” with input from international scientists discussing and critiquing the results in the paper.  

 

Please note that when we scientists CRITIQUE a paper it does not mean CRITICIZE it.  A critique is merely an in depth analysis of the results and conclusions with an open discussion on the paper.  This is part of the normal peer review process.

 

Below is the original Tweet by Dr. Eric Topol as well as the ensuing tweet thread

 

https://twitter.com/EricTopol/status/1241442247133900801?s=20

 

Within the tweet thread it was discussed some of the limitations or study design flaws of the referenced paper leading the scientists in this impromptu discussion that the study could not reasonably conclude that hydroxychloroquine was not a reliable therapeutic for this coronavirus strain.

 

The lesson: The public has to realize CRITIQUE does not mean CRITICISM.

 

Scientific discourse has to occur to allow for the proper critique of results.  When this is allowed science becomes better, more robust, and we protect ourselves from maybe heading down an incorrect path, which may have major impacts on a clinical outcome, in this case.

 

 

2.  Lack of communication and connection between patients and those involved in the healthcare industry

 

In normal times, it is imperative for the patient-physician relationship to be intact in order for the physician to be able to communicate proper information to their patient during and after therapy/care.  In these critical times, this relationship and good communication skills becomes even more important.

 

Recently, I have had multiple communications, either through Twitter, Facebook, and other social media outlets with cancer patients, cancer advocacy groups, and cancer survivorship forums concerning their risks of getting infected with the coronavirus and how they should handle various aspects of their therapy, whether they were currently undergoing therapy or just about to start chemotherapy.  This made me realize that there were a huge subset of patients who were not receiving all the information and support they needed; namely patients who are immunocompromised.

 

These are patients represent

  1. cancer patient undergoing/or about to start chemotherapy
  2. Patients taking immunosuppressive drugs: organ transplant recipients, patients with autoimmune diseases, multiple sclerosis patients
  3. Patients with immunodeficiency disorders

 

These concerns prompted me to write a posting curating the guidance from National Cancer Institute (NCI) designated cancer centers to cancer patients concerning their risk to COVID19 (which can be found here).

 

Surprisingly, there were only 14 of the 51 US NCI Cancer Centers which had posted guidance (either there own or from organizations like NCI or the National Cancer Coalition Network (NCCN).  Most of the guidance to patients had stemmed from a paper written by Dr. Markham of the Fred Hutchinson Cancer Center in Seattle Washington, the first major US city which was impacted by COVID19.

 

Also I was surprised at the reactions to this posting, with patients and oncologists enthusiastic to discuss concerns around the coronavirus problem.  This led to having additional contact with patients and oncologists who, as I was surprised, are not having these conversations with each other or are totally confused on courses of action during this pandemic.  There was a true need for each party, both patients/caregivers and physicians/oncologists to be able to communicate with each other and disseminate good information.

 

Last night there was a Tweet conversation on Twitter #OTChat sponsored by @OncologyTimes.  A few tweets are included below

https://twitter.com/OncologyTimes/status/1242611841613864960?s=20

https://twitter.com/OncologyTimes/status/1242616756658753538?s=20

https://twitter.com/OncologyTimes/status/1242615906846547978?s=20

 

The Lesson:  Rapid Communication of Vital Information in times of stress is crucial in maintaining a good patient/physician relationship and preventing Misinformation.

 

3.  Socio-geographical Inequalities in the US Healthcare System

It has become very clear that the US healthcare system is fractioned and multiple inequalities (based on race, sex, geography, socio-economic status, age) exist across the whole healthcare system.  These inequalities are exacerbated in times of stress, especially when access to care is limited.

 

An example:

 

On May 12, 2015, an Amtrak Northeast Regional train from Washington, D.C. bound for New York City derailed and wrecked on the Northeast Corridor in the Port Richmond neighborhood of Philadelphia, Pennsylvania. Of 238 passengers and 5 crew on board, 8 were killed and over 200 injured, 11 critically. The train was traveling at 102 mph (164 km/h) in a 50 mph (80 km/h) zone of curved tracks when it derailed.[3]

Some of the passengers had to be extricated from the wrecked cars. Many of the passengers and local residents helped first responders during the rescue operation. Five local hospitals treated the injured. The derailment disrupted train service for several days. 

(Source Wikipedia https://en.wikipedia.org/wiki/2015_Philadelphia_train_derailment)

What was not reported was the difficulties that first responders, namely paramedics had in finding an emergency room capable of taking on the massive load of patients.  In the years prior to this accident, several hospitals, due to monetary reasons, had to close their emergency rooms or reduce them in size. In addition only two in Philadelphia were capable of accepting gun shot victims (Temple University Hospital was the closest to the derailment but one of the emergency rooms which would accept gun shot victims. This was important as Temple University ER, being in North Philadelphia, is usually very busy on any given night.  The stress to the local health system revealed how one disaster could easily overburden many hospitals.

 

Over the past decade many hospitals, especially rural hospitals, have been shuttered or consolidated into bigger health systems.  The graphic below shows this

From Bloomberg: US Hospital Closings Leave Patients with Nowhere to go

 

 

https://images.app.goo.gl/JdZ6UtaG3Ra3EA3J8

 

Note the huge swath of hospital closures in the midwest, especially in rural areas.  This has become an ongoing problem as the health care system deals with rising costs.

 

Lesson:  Epidemic Stresses an already stressed out US healthcare system

 

Please see our Coronavirus Portal at

https://pharmaceuticalintelligence.com/coronavirus-portal/

 

for more up-to-date scientific, clinical information as well as persona stories, videos, interviews and economic impact analyses

and @pharma_BI

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What drug interfered with the performance of Sharapova?

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Meldonium — The Drug That Brought Down Sharapova

Gayle Nicholas Scott, PharmD

When tennis player Maria Sharapova recently revealed that she had tested positive for the banned drug meldonium, the reaction of most healthcare providers was, “What is it?”

Meldonium is manufactured and sold as Mildronate by the pharmaceutical company Grindeks in the Baltic nation of Latvia. Meldonium is not available in the United States or elsewhere in the European Union (it was grandfathered in Latvia) other than via purchase on the Internet.

The World Anti-Doping Agency classifies meldonium as a “metabolic modulator” and moved the drug from its watch list to its list of banned substances in January 2016.

Other “metabolic modulators” are insulin and trimetazidine, an anti-ischemic metabolic agent that increases myocardial glucose utilization through inhibition of fatty acid metabolism.[1,2] Trimetazidine is approved in the European Union for the treatment of angina, but it is not approved in the United States.

The chemical name for meldonium is trimethylhydrazinium propionate. Meldonium works by decreasing the availability of levocarnitine (L-carnitine). L-carnitine is found naturally in milk and meats, and also can be synthesized by the body from lysine and methionine with the help of gamma-butyrobetaine hydroxylase. L-carnitine helps move long-chain fatty acids into the mitochondria for oxidation and energy production in the muscles.

Ironically, L-carnitine, which meldonium inhibits, is taken as a dietary supplement alone and as an ingredient in energy drinks to increase athletic performance. (L-carnitine is available in the United States as the prescription drug Carnitor®, which is indicated for carnitine deficiency owing to inborn errors of metabolism and for end-stage renal disease requiring dialysis.) After two decades of research, no consistent evidence has emerged indicating that carnitine supplements can improve exercise or physical performance. Carnitine supplements do not appear to increase the body’s use of oxygen or improve metabolic status when exercising, and may not increase the amount of carnitine in muscle.[3,4]Carnitine is not on the list of banned substances.[1]

As a modulator of L-carnitine metabolism, meldonium inhibits gamma-butyrobetaine hydroxylase and L-carnitine transmembrane transport of long-chain fatty acids, thus decreasing L-carnitine levels in tissue and plasma. Reducing the amount of bioavailable L-carnitine shifts the source of metabolic energy production from fatty acid oxidation to glucose metabolism. Aerobic glucose oxidation consumes less oxygen than fatty acid oxidation and increases the effectiveness of adenosine triphosphate (ATP) generation. Additionally, meldonium appears to increase glucose uptake. In ischemic conditions (hypoxia), meldonium appears to restore the balance between cellular oxygen supply and demand, and prevents ATP transport impairment.[3,5]

All published clinical efficacy studies on meldonium, except one,[6] are in Russian. Abstracts of randomized controlled trials have reported the efficacy of meldonium in reducing angina, arrhythmias, and anxiety and other early sequelae of myocardial infarction[7-10]; as an “adaptogen” in patients with cardiovascular disease[11,12]; and in treating angina and reducing myocardial ischemia after percutaneous coronary intervention,[6,13,14] heart failure,[15] and diabetic peripheral neuropathy.[16] Doses, when included in the abstracts, ranged from 750 to 1000 mg per day. Only one abstract mentioned adverse effects, stating that none occurred.[7]

A pharmacokinetic study of meldonium showed that the drug has a dose-dependent half-life and volume of distribution with accumulation on multiple-dose administration. In eight healthy volunteers who received meldonium for 13 days, almost all reported insomnia, half reported burping, and one quarter reported “dreaminess.” No serious adverse effects were reported.[17]

A study in healthy, nonvegetarian volunteers receiving 1000 mg meldonium per day for 4 weeks showed that plasma concentrations of L-carnitine decreased by 18%. Urine samples showed an increase in L-carnitine excretion. Adverse effects were not mentioned.[18] Meldonium is excreted in the urine largely unchanged, making urine testing a valid monitor presence of meldonium.[19]

No long-term studies on the safety and efficacy of meldonium have been published. No studies on the effect of meldonium on athletic performance in humans have been published. One study on the reliability of urine testing in professional sports[19]mentions an article and an abstract, but neither of those appears in PubMed. The abstract purports to be a review of “recent studies on mildronate especially in fields associated with physical work capabilities and sport” but cites only the study mentioned in the urine testing review.[20] Most articles about meldonium cited on PubMed are by Latvian authors.

Animal research suggests the potential usefulness of meldonium in Alzheimer disease,[21-23] Parkinson disease,[24,25] and diabetes.[26-29] Meldonium increased sexual activity in boars[30] but not in male rats.[31] Research in rodents found that meldonium can cause carnitine deficiency in offspring, so the drug should not be taken in pregnancy.[32]

Because meldonium is excreted renally, serum levels may be higher in patients with reduced kidney function, and the drug may accumulate with repeated dosing.[19] L-carnitine appears to antagonize the effects of meldonium[33]; otherwise, drug interactions are not known.

To recap, meldonium is an interesting drug developed by Latvian researchers. Published research suggests that it may be an effective treatment for cardiovascular diseases, such as angina. Little information about its adverse effects has been published, however, and the long-term safety of meldonium is not known. And although reliable research on meldonium’s use for athletic performance is not available, the World Anti-Doping Agency has declared it a banned substance.

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The late Cambridge Mayor Alfred Vellucci welcomed Life Sciences Labs to Cambridge, MA – June 1976

Reporter: Aviva Lev-Ari, PhD, RN

How Cambridge became the Life Sciences Capital

Worth watching is the video below, which captures the initial Cambridge City Council hearing on recombinant DNA research from June 1976. The first speaker is the late Cambridge mayor Alfred Vellucci.

Vellucci hoped to pass a two-year moratorium on gene splicing in Cambridge. Instead, the council passed a three-month moratorium, and created a board of nine Cambridge citizens — including a nun and a nurse — to explore whether the work should be allowed, and if so, what safeguards would be necessary. A few days after the board was created, the pro and con tables showed up at the Kendall Square marketplace.

At the time, says Phillip Sharp, an MIT professor, Cambridge felt like a manufacturing town that had seen better days. He recalls being surrounded by candy, textile, and leather factories. Sharp hosted the citizens review committee at MIT, explaining what the research scientists there planned to do. “I think we built a relationship,” he says.

By early 1977, the citizens committee had proposed a framework to ensure that any DNA-related experiments were done under fairly stringent safety controls, and Cambridge became the first city in the world to regulate research using genetic material.

 

WATCH VIDEO

How Cambridge became the life sciences capital

Scott Kirsner can be reached at kirsner@pobox.com. Follow him on Twitter@ScottKirsner and on betaboston.com.

SOURCE

How Cambridge became the life sciences capital

http://www.betaboston.com/news/2016/03/17/how-cambridge-became-the-life-sciences-capital/

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Supreme Court reverses Zimmer win in $20m knee implant lawsuit

Reported by: Irina Robu, PhD

The Pennsylvania Supreme Court yesterday reversed a state appeals court’s decision to overturn a $20 million verdict against in a knee implant lawsuit. Margo Pollet had a double knee replacement procedure in 2006 using Zimmer’s Gender Solutions devices but after making a Zimmer promotional video which included riding a bicycle and running on treadmill, she claimed that it damaged her knees. She sued for negligence saying the injuries occured during filming the video. A jury awarded Polett millions in damages after finding that Zimmer was 34% culpable. The jury also put 30% of the blame on Polett herself and 36% on the marketing firm Public Communications for its involvement with the ad.

The Pennsylvania Superior Court last October ruled that the lower court incorrectly shifted the burden of proof onto Zimmer by asking the company to provide alternative explanations for Polett’s revisions surgeries, thus leading the jury to a potentially false conclusion, and ordered a new trial. 

“In sum, the trial court’s ruling that Dr. Booth’s expert testimony as to causation was not barred by [Pennsylvania law] was amply supported by the evidence of record, and thus was reasonable. Consequently, we conclude that the trial court did not abuse its discretion in allowing Dr. Booth to render an expert opinion at trial, and that the  Superior Court erred by reassessing the evidence relied upon by the trial court in making its ruling, and by supplanting the trial court’s findings with its own evaluation of that evidence. We, therefore, reverse the order of the Superior Court as to this issue,” McCloskey Todd wrote.

The Supreme Court ordered the Superior Court to review whether the trial court was wrong to deny the defendants’ bid to overturn the verdict.

Source

http://www.massdevice.com/pennsylvania-supreme-court-reverses-zimmer-win-in-20m-knee-implant-lawsuit/?utm_source=newsletter-151031&utm_medium=email&utm_campaign=newsletter-151031&utm_source=hs_email&utm_medium=email&utm_content=23330293&_hsenc=p2ANqtz–nywdqI8Oozk—hLR5sGhUzi28TI0dySIJ7JSoVr72yV8Y9K535Br78ZKs9nHBieb7asND2eZS2iTcUV9OHRqCaUTZlvqQHU7BNH4C6r82Zh13vQ&_hsmi=23330293

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pathway and network analysis of complex ‘omics data

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

While blood tests can be used to detect some cancers, the FDA said a San Diego company has no proof its blood test works in patients who have not already been diagnosed with some form of the disease.

WASHINGTON, Sept. 25 (UPI) — A San Diego company selling an early cancer detection test was notified by the U.S. Food and Drug Administration it can find no evidence the test actually works, and is concerned it could prove to be harmful for some people.

Pathway Genomics debuted its CancerIntercept test in early September with claims it can detect cancer cell DNA in the blood, picking up mutations linked to as many as 10 different cancers. The goal is to catch cancer early in people who are “otherwise healthy” and not showing symptoms of the disease.

“Based on our review of your promotional materials and the research publication cited above, we believe you are offering a high risk test that has not received adequate clinical validation and may harm the public health,” said FDA Deputy Director James L. Woods in a letter to the company.

CancerIntercept is billed by the company as a blood test looking for DNA fragments in the bloodstream and testing them for 96 genomic markers it says are found in several specific tumor types.

The direct-to-consumer test can be purchased through the Pathway Genomics website, with programs ranging from a one-time test to a quarterly “subscription” for people who want regular testing.

The company states, in several sections of its website, “the presence of one or more of these genomic markers in a patient’s bloodstream may indicate that the patient has a previously undetected cancer. However, the test is not diagnostic, and thus, follow-up screening and clinical testing would be required to confirm the presence or absence of a specific cancer in the patient.”

The FDA is concerned that people may seek treatment for tumors that do not require medical attention, or spend money and possibly seek out treatment they do not need at all — in either case, unnecessary treatment for cancer is potentially harmful to people, the agency said.

CancerIntercept has not been approved by the FDA for use as a medical device, nor has it been subjected to peer review as most tests of its type would be. The company published a white paper on its website which outlines how the test works, supporting its efficacy with references to several clinical trials on detection of mutated DNA in the bloodstream.

Glenn Braunstein, Chief Medical Officer at Pathway Genomics, told The VergePathway had validated its tests with “hundreds” of patients, though those patients had well-defined, often advanced cancers.

In the letter from the FDA, Woods requests the company provide a timeline for meeting with the agency to review plans for future longitudinal studies on the product and specific details on studies that have been conducted before it was made available to consumers.

http://www.upi.com/Health_News/2015/09/25/FDA-Start-ups-cancer-blood-test-may-be-harmful/4191443181676/

The clinical laboratory is an essential player in the treatment of cancer providing a diagnostic, potentially a prognostic, and follow-up treatment armamentarium.  The laboratory diagnostics industry has grown over the last half century into  a highly accurate, well regulated industry with highly automated and point of care technologies.  Prior to introduction, the tests that are put on the market have to be validated prior to introduction.

How are they validated?

The most common approach is for the test to be used concomitantly with treatment in a clinical trial. Measurements may be made prior to surgical biopsy and treatment, and at a month or 6 months to a year later.  The pharmaceutical and diagnostics industries are independent, even though a large company may have both pharmaceutical and diagnostic divisions.  Consequently, the integration of diagnostics and therapeutics occurs on the front lines of patient care.

How this discrepancy between the FDA and the manufacturer could occur is not clear because prior to introduction, the test would have to be rigorously reviewed by the American Association for Clinical Chemistry, the largest and most competent organization to cover the scientific work, having industry-based committees.  The only problem is that the companies may have products that are patented and have competing claims or interests. This is perhaps most likely to be problematic in the competitive environment of  genomics testing.

The company here reported on is Pathway Genomics, that offers Ingenuity for pathway and variant analysis.  There is no concern about the analysis methods, that are well studied.  The concern is the validation of such method for screening of patients without prior diagnosis.

Model, analyze, and understand the complex biological and chemical systems at the core of life science research with IPA

QIAGEN’S Ingenuity Pathway Analysis (IPA) has been broadly adopted by the life science research community and is cited in thousands of peer-reviewed journal articles.

https://youtu.be/_HDkjuxYRcY

https://youtu.be/_HDkjuxYRcY?t=25

For the analysis and interpretation of ’omics data
Market Leading Pathway Analysis
Unlock the insights buried in experimental data by quickly identifying relationships, mechanisms, functions, and pathways of relevance.
Predictive Causal Analytics
Powerful causal analytics at your fingertips help you to build a more complete regulatory picture and a better understanding of the biology underlying a given gene expression study.
NGS/RNA-Seq Data Analysis
Get a better understanding of the isoform-specific biology resulting from RNA-Seq experiments.
Identify causal variants from human sequencing data
Ingenuity IPA Interpret Biological Meaning Graphic

http://www.ingenuity.com/wp-content/uploads/2014/01/variant-analyisis-interpretation.png

Rapidly Identify and Prioritize Variants

Ingenuity Variant Analysis combines analytical tools and integrated content to help you rapidly identify and prioritize variants by drilling down to a small, targeted subset of compelling variants based both upon published biological evidence and your own knowledge of disease biology. With Variant Analysis, you can interrogate your variants from multiple biological perspectives, explore different biological hypotheses, and identify the most promising variants for follow-up.

Variant Analysis used in NCI-60 Interpretation of Genomic Variants

The NCI-60 Data Set offers tremendous promise in the development and prescription of cancer drugs

97% of surveyed researchers are satisfied with the ease of use of Ingenuity Variant Analysis and we are honored that they chose to share the data through our Publish tool.

See the research verified by TechValidate

“Being a bioinformatician, I appreciated the speed and the complexity of analysis. Without Variant Analysis, I couldn’t have completed the analysis of 700 exomes in such a short time …. I found Variant Analysis very intuitive and easy to use.”

Francesco Lescai, Senior Research Associate in Genome Analysis, University College of London.

This appears to be the new rocky road to verification for validity in diagnostic and treatment application.

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The Vibrant Philly Biotech Scene: Focus on KannaLife Sciences and the Discipline and Potential of Pharmacognosy

Curator and Interviewer: Stephen J. Williams, Ph.D.

 

philly2nightThis post is the third in a series of posts highlighting interviews with Philadelphia area biotech startup CEO’s and show how a vibrant biotech startup scene is evolving in the city as well as the Delaware Valley area. Philadelphia has been home to some of the nation’s oldest biotechs including Cephalon, Centocor, hundreds of spinouts from a multitude of universities as well as home of the first cloned animal (a frog), the first transgenic mouse, and Nobel laureates in the field of molecular biology and genetics. Although some recent disheartening news about the fall in rankings of Philadelphia as a biotech hub and recent remarks by CEO’s of former area companies has dominated the news, biotech incubators like the University City Science Center and Bucks County Biotechnology Center as well as a reinvigorated investment community (like PCCI and MABA) are bringing Philadelphia back. And although much work is needed to bring the Philadelphia area back to its former glory days (including political will at the state level) there are many bright spots such as the innovative young companies as outlined in these posts.

In today’s post, I had the opportunity to talk with both Dr. William Kinney, Chief Scientific Officer and Thoma Kikis, Founder/CMO of KannaLife Sciences based in the Pennsylvania Biotech Center of Bucks County.   KannaLifeSciences, although highlighted in national media reports and Headline news (HLN TV)for their work on cannabis-derived compounds, is a phyto-medical company focused on the discipline surrounding pharmacognosy, the branch of pharmacology dealing with natural drugs and their constituents.

Below is the interview with Dr. Kinney and Mr. Kikis of KannaLife Sciences and Leaders in Pharmaceutical Business Intelligence (LPBI)

 

PA Biotech Questions answered by Dr. William Kinney, Chief Scientific Officer of KannaLife Sciences

 

 

LPBI: Your parent company   is based in New York. Why did you choose the Bucks County Pennsylvania Biotechnology Center?

 

Dr. Kinney: The Bucks County Pennsylvania Biotechnology Center has several aspects that were attractive to us.  They have a rich talent pool of pharmaceutically trained medicinal chemists, an NIH trained CNS pharmacologist,  a scientific focus on liver disease, and a premier natural product collection.

 

LBPI: The Blumberg Institute and Natural Products Discovery Institute has acquired a massive phytochemical library. How does this resource benefit the present and future plans for KannaLife?

 

Dr. Kinney: KannaLife is actively mining this collection for new sources of neuroprotective agents and is in the process of characterizing the active components of a specific biologically active plant extract.  Jason Clement of the NPDI has taken a lead on these scientific studies and is on our Advisory Board. 

 

LPBI: Was the state of Pennsylvania and local industry groups support KannaLife’s move into the Doylestown incubator?

 

Dr. Kinney: The move was not State influenced by state or industry groups. 

 

LPBI: Has the partnership with Ben Franklin Partners and the Center provided you with investment opportunities?

 

Dr. Kinney: Ben Franklin Partners has not yet been consulted as a source of capital.

 

LPBI: The discipline of pharmacognosy, although over a century old, has relied on individual investigators and mainly academic laboratories to make initial discoveries on medicinal uses of natural products. Although there have been many great successes (taxol, many antibiotics, glycosides, etc.) many big pharmaceutical companies have abandoned this strategy considering it a slow, innefective process. Given the access you have to the chemical library there at Buck County Technology Center, the potential you had identified with cannabanoids in diseases related to oxidative stress, how can KannaLife enhance the efficiency of finding therapeutic and potential preventive uses for natural products?

 

Dr. Kinney: KannaLife has the opportunity to improve upon natural molecules that have shown medically uses, but have limitations related to safety and bioavailability. By applying industry standard medicinal chemistry optimization and assay methods, progress is being made in improving upon nature.  In addition KannaLife has access to one of the most commercially successful natural products scientists and collections in the industry.

 

LPBI: How does the clinical & regulatory experience in the Philadelphia area help a company like Kannalife?

 

Dr. Kinney: Within the region, KannaLife has access to professionals in all areas of drug development either by hiring displaced professionals or partnering with regional contract research organizations.

 

LPBI  You are focusing on an interesting mechanism of action (oxidative stress) and find your direction appealing (find compounds to reverse this, determine relevant disease states {like HCE} then screen these compounds in those disease models {in hippocampal slices}).  As oxidative stress is related to many diseases are you trying to develop your natural products as preventative strategies, even though those type of clinical trials usually require massive numbers of trial participants or are you looking to partner with a larger company to do this?

 

Dr. Kinney: Our strategy is to initially pursue Hepatic Encephalophy (HE) as the lead orphan disease indication and then partner with other organizations to broaden into other areas that would benefit from a neuroprotective agent.  It is expected the HE will be responsive to an acute treatment regimen.   We are pursuing both natural products and new chemical entities for this development path.

 

 

General Questions answered by Thoma Kikis, Founder/CMO of KannaLife Sciences

 

LPBI: How did KannaLife get the patent from the National Institutes of Health?

 

My name is Thoma Kikis I’m the co-founder of KannaLife Sciences. In 2010, my partner Dean Petkanas and I founded KannaLife and we set course applying for the exclusive license of the ‘507 patent held by the US Government Health and Human Services and National Institutes of Health (NIH). We spent close to 2 years working on acquiring an exclusive license from NIH to commercially develop Patent 6,630,507 “Cannabinoids as Antioxidants and Neuroprotectants.” In 2012, we were granted exclusivity from NIH to develop a treatment for a disease called Hepatic Encephalopathy (HE), a brain liver disease that stems from cirrhosis.

 

Cannabinoids are the chemicals that compose the Cannabis plant. There are over 85 known isolated Cannabinoids in Cannabis. The cannabis plant is a repository for chemicals, there are over 400 chemicals in the entire plant. We are currently working on non-psychoactive cannabinoids, cannabidiol being at the forefront.

 

As we started our work on HE and saw promising results in the area of neuroprotection we sought out another license from the NIH on the same patent to treat CTE (Chronic Traumatic Encephalopathy), in August of 2014 we were granted the additional license. CTE is a concussion related traumatic brain disease with long term effects mostly suffered by contact sports players including football, hockey, soccer, lacrosse, boxing and active military soldiers.

 

To date we are the only license holders of the US Government held patent on cannabinoids.

 

 

LPBI: How long has this project been going on?

 

We have been working on the overall project since 2010. We first started work on early research for CTE in early-2013.

 

 

LPBI: Tell me about the project. What are the goals?

 

Our focus has always been on treating diseases that effect the Brain. Currently we are looking for solutions in therapeutic agents designed to reduce oxidative stress, and act as immuno-modulators and neuroprotectants.

 

KannaLife has an overall commitment to discover and understand new phytochemicals. This diversification of scientific and commercial interests strongly indicates a balanced and thoughtful approach to our goals of providing standardized, safer and more effective medicines in a socially responsible way.

 

Currently our research has focused on the non-psychoactive cannabidiol (CBD). Exploring the appropriate uses and limitations and improving its safety and Metered Dosing. CBD has a limited therapeutic window and poor bioavailability upon oral dosing, making delivery of a consistent therapeutic dose challenging. We are also developing new CBD-like molecules to overcome these limitations and evaluating new phytochemicals from non-regulated plants.

 

KannaLife’s research is led by experienced pharmaceutically trained professionals; Our Scientific team out of the Pennsylvania Biotechnology Center is led by Dr. William Kinney and Dr. Douglas Brenneman both with decades of experience in pharmaceutical R&D.

 

 

LPBI: How do cannabinoids help neurological damage? -What sort of neurological damage do they help?

 

Cannabinoids and specifically cannabidiol work to relieve oxidative stress, and act as immuno-modulators and neuroprotectants.

 

So far our pre-clinical results show that cannabidiol is a good candidate as a neuroprotectant as the patent attests to. Our current studies have been to protect neuronal cells from toxicity. For HE we have been looking specifically at ammonia and ethanol toxicity.

 

 

– How did it go from treating general neurological damage to treating CTE? Is there any proof yet that cannabinoids can help prevent CTE? What proof?

 

We started examining toxicity first with ammonia and ethanol in HE and then posed the question; If CBD is a neuroprotectant against toxicity then we need to examine what it can do for other toxins. We looked at CTE and the toxin that causes it, tau. We just acquired the license in August from the NIH for CTE and are beginning our pre-clinical work in the area of CTE now with Dr. Ron Tuma and Dr. Sara Jane Ward at Temple University in Philadelphia.

 

 

LPBI: How long until a treatment could be ready? What’s the timeline?

 

We will have research findings in the coming year. We plan on filing an IND (Investigational New Drug application) with the FDA for CBD and our molecules in 2015 for HE and file for CTE once our studies are done.

 

 

LPBI: What other groups are you working with regarding CTE?

 

We are getting good support from former NFL players who want solutions to the problem of concussions and CTE. This is a very frightening topic for many players, especially with the controversy and lawsuits surrounding it. I have personally spoken to several former NFL players, some who have CTE and many are frightened at what the future holds.

 

We enrolled a former player, Marvin Washington. Marvin was an 11 year NFL vet with NY Jets, SF 49ers and won a SuperBowl on the 1998 Denver Broncos. He has been leading the charge on KannaLife’s behalf to raise awareness to the potential solution for CTE.

 

We tried approaching the NFL in 2013 but they didn’t want to meet. I can understand that they don’t want to take a position. But ultimately, they’re going to have to make a decision and look into different research to treat concussions. They have already given the NIH $30 Million for research into football related injuries and we hold a license with the NIH, so we wanted to have a discussion. But currently cannabinoids are part of their substance abuse policy connected to marijuana. Our message to the NFL is that they need to lead the science, not follow it.

 

Can you imagine the NFL’s stance on marijuana treating concussions and CTE? These are topics they don’t want to touch but will have to at some point.

 

LPBI: Thank you both Dr. Kinney and Mr. Kikis.

 

Please look for future posts in this series on the Philly Biotech Scene on this site

Also, if you would like your Philadelphia biotech startup to be highlighted in this series please contact me or

http://pharmaceuticalintelligence.com at:

sjwilliamspa@comcast.net or @StephenJWillia2  or @pharma_BI.

Our site is read by ~ thousand international readers DAILY and thousands of Twitter followers including venture capital.

 

Other posts on this site in this VIBRANT PHILLY BIOTECH SCENE SERIES OR referring to PHILADELPHIA BIOTECH include:

The Vibrant Philly Biotech Scene: Focus on Computer-Aided Drug Design and Gfree Bio, LLC

RAbD Biotech Presents at 1st Pitch Life Sciences-Philadelphia

The Vibrant Philly Biotech Scene: Focus on Vaccines and Philimmune, LLC

What VCs Think about Your Pitch? Panel Summary of 1st Pitch Life Science Philly

1st Pitch Life Science- Philadelphia- What VCs Really Think of your Pitch

LytPhage Presents at 1st Pitch Life Sciences-Philadelphia

Hastke Inc. Presents at 1st Pitch Life Sciences-Philadelphia

PCCI’s 7th Annual Roundtable “Crowdfunding for Life Sciences: A Bridge Over Troubled Waters?” May 12 2014 Embassy Suites Hotel, Chesterbrook PA 6:00-9:30 PM

Pfizer Cambridge Collaborative Innovation Events: ‘The Role of Innovation Districts in Metropolitan Areas to Drive the Global an | Basecamp Business

Mapping the Universe of Pharmaceutical Business Intelligence: The Model developed by LPBI and the Model of Best Practices LLC

 

 

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Why did this occur? The matter of Individual Actions Undermining Trust, The Patent Dilemma and The Value of a Clinical Trials


Why did this occur? The matter of Individual Actions Undermining Trust, The Patent Dilemma and The Value of a Clinical Trials

Reporter and Curator: Larry H. Bernstein, MD, FCAP

 

he large amount of funding tied to continued research and support of postdoctoral fellows leads one to ask how following the money can lead to discredited work in th elite scientific community.

Moreover, the pressure to publish in prestigious journals with high impact factors is a road to academic promotion.  In the last twenty years, it is unusual to find submissions for review with less than 6-8 authors, with the statement that all contributed to the work.  These factors can’t be discounted outright, but it is easy for work to fall through the cracks when a key investigator has over 200 publications and holds tenure in a great research environment.  But that is where we find ourselves today.

There is another issue that comes up, which is also related to the issue of carrying out research, and then protecting the work for commercialization.  It is more complicated in the sense that it is necessary to determine whether there is prior art, and then there is the possibility that after the cost of filing patent and a 6 year delay in obtaining protection, there is as great a cost in bringing the patent to finasl production.

I.  Individual actions undermining trust.

II. The patent dilemma.

III. The value of a clinical trial.

IV. The value contributions of RAP physicians
(radiologists, anesthesiologists, and pathologists – the last for discussion)
Those who maintain and inform the integrity of medical and surgical decisions

 

I. Top heart lab comes under fire

Kelly Servick

Science 18 July 2014: Vol. 345 no. 6194 p. 254 DOI: 10.1126/science.345.6194.25

 

In the study of cardiac regeneration, Piero Anversa is among the heavy hitters. His research into the heart’s repair mechanisms helped kick-start the field of cardiac cell therapy (see main story). After more than 4 decades of research and 350 papers, he heads a lab at Harvard Medical School’s Brigham and Women’s Hospital (BWH) in Boston that has more than $6 million in active grant funding from the National Institutes of Health (NIH). He is also an outspoken voice in a field full of disagreement.

So when an ongoing BWH investigation of the lab came to light earlier this year, Anversa’s colleagues were transfixed. “Reactions in the field run the gamut from disbelief to vindication,” says Mark Sussman, a cardiovascular researcher at San Diego State University in California who has collaborated with Anversa. By Sussman’s account, Anversa’s reputation for “pushing the envelope” and “challenging existing dogma” has generated some criticism. Others, however, say that the disputes run deeper—to doubts about a cell therapy his lab has developed and about the group’s scientific integrity. Anversa told Science he was unable to comment during the investigation.

“People are talking about this all the time—at every scientific meeting I go to,” says Charles Murry, a cardiovascular pathologist at the University of Washington, Seattle. “It’s of grave concern to people in the field, but it’s been frustrating,” because no information is available about BWH’s investigation. BWH would not comment for this article, other than to say that it addresses concerns about its researchers confidentially.

In April, however, the journal Circulation agreed to Harvard’s request to retract a 2012 paper on which Anversa is a corresponding author, citing “compromised” data. The Lancet also issued an “Expression of Concern” about a 2011 paper reporting results from a clinical trial, known as SCIPIO, on which Anversa collaborated. According to a notice from the journal, two supplemental figures are at issue.

For some, Anversa’s status has earned him the benefit of the doubt. “Obviously, this is very disconcerting,” says Timothy Kamp, a cardiologist at the University of Wisconsin, Madison, but “I would be surprised if it was an implication of a whole career of research.”

Throughout that career, Anversa has argued that the heart is a prolific, lifelong factory for new muscle cells. Most now accept the view that the adult heart can regenerate muscle, but many have sparred with Anversa over his high estimates for the rate of this turnover, which he maintained in the retracted Circulation paper.

Anversa’s group also pioneered a method of separating cells with potential regenerative abilities from other cardiac tissue based on the presence of a protein called c-kit. After publishing evidence that these cardiac c-kit+cells spur new muscle growth in rodent hearts, the group collaborated in the SCIPIO trial to inject them into patients with heart failure. In The Lancet, the scientists reported that the therapy was safe and showed modest ability to strengthen the heart—evidence that many found intriguing and provocative. Roberto Bolli, the cardiologist whose group at the University of Louisville in Kentucky ran the SCIPIO trial, plans to test c-kit+ cells in further clinical trials as part of the NIH-funded Cardiovascular Cell Therapy Research Network.

But others have been unable to reproduce the dramatic effects Anversa saw in animals, and some have questioned whether these cells really have stem cell–like properties. In May, a group led by Jeffery Molkentin, a molecular biologist at Cincinnati Children’s Hospital Medical Center in Ohio, published a paper in Nature tracing the genetic lineage of c-kit+ cells that reside in the heart. He concluded that although they did make new muscle cells, the number is “astonishingly low” and likely not enough to contribute to the repair of damaged hearts. Still, Molkentin says that he “believe[s] in their therapeutic potential” and that he and Anversa have discussed collaborating.

Now, an anonymous blogger claims that problems in the Anversa lab go beyond controversial findings. In a letter published on the blog Retraction Watch on 30 May, a former research fellow in the Anversa lab described a lab culture focused on protecting the c-kit+ cell hypothesis: “[A]ll data that did not point to the ‘truth’ of the hypothesis were considered wrong,” the person wrote. But another former lab member offers a different perspective. “I had a great experience,” says Federica Limana, a cardiovascular disease researcher at IRCCS San Raffaele Pisana in Rome who spent 2 years of her Ph.D. work with the group in 1999 and 2000, as it was beginning to investigate c-kit+ cells. “In that period, there was no such pressure” to produce any particular result, she says.

Accusations about the lab’s integrity, combined with continued silence from BWH, are deeply troubling for scientists who have staked their research on theories that Anversa helped pioneer. Some have criticized BWH for requesting retractions in the midst of an investigation. “Scientific reputations and careers hang in the balance,” Sussman says, “so everyone should wait until all facts are clearly and fully disclosed.”

 

II.  Trolling Along: Recent Commotion About Patent Trolls

July 17, 2014

PriceWaterhouseCoopers recently released a study about 2014 Patent Litigation. PwC’s ultimate conclusion was that case volume increased vastly and damages continue a general decline, but what’s making headlines everywhere is that “patent trolls” now account for 67% of all new patent lawsuits (see, e.g., Washington Post and Fast Company).

Surprisingly, looking at PwC’s study, the word “troll” is not to be found. So, with regard to patent trolls, what does this study really mean for companies, patent owners and casual onlookers?

First of all, who are these trolls?

“Patent Troll” is a label applied to patent owners who do not make or manufacture a product, or offer a service. Patent trolls live (and die) by suing others for allegedly practicing an invention that is claimed by their patents.

The politically correct term is Non-practicing Entity (NPE). PwC solely uses the term NPE, which it defines as an entity that does not have the capability to design, manufacture, or distribute products with features protected by the patent.

So, what’s so bad about them?

The common impression of an NPEs is a business venture looking to collect and monetize assets (i.e., patents). In the most basic strategy, an NPE typically buys patents with broad claims that cover a wide variety of technologies and markets, and then sues a large group of alleged patent infringers in the hope to collect a licensing royalty or a settlement. NPEs typically don’t want to spend money on a trial unless they have to, and one tactic uses settlements with smaller businesses to build a “war chest” for potential suits with larger companies.

NPEs initiating a lawsuit can be viewed positively, such as a just defense of the lowly inventor who sold his patent to someone (with deeper pockets) who could fund the litigation to protect the inventor’s hard work against a mega-conglomerate who ripped off his idea.

Or NPE litigation can be seen negatively, such as an attorney’s demand letter on behalf of an anonymous shell corporation to shake down dozens of five-figure settlements from all the local small businesses that have ever used a fax machine.

NPEs can waste a company’s valuable time and resources with lawsuits, yet also bring value to their patent portfolios by energizing a patent sales and licensing market. There are unscrupulous NPEs, but it’s hardly the black and white situation that some media outlets are depicting.

What did PwC say about trolls?

Well, the PwC study looked at the success rates and awards of patent litigation decisions. One conclusion is that damages awards for NPEs averaged more than triple those for practicing entities over the last four years. We’ll come back to this statistic.

Another key observation is that NPEs have been successful 25% of the time overall, versus 35% for practicing entities. This makes sense because of the burden of proof the NPEs carry as a plaintiff at trial and the relative lack of success for NPEs at summary judgment. However, PwC’s report states that both types of entities win about two-thirds of their trials.

But what about this “67% of all patent trials are initiated by trolls” discussion?

The 67% number comes from the RPX Corporation’s litigation report (produced January 2014) that quantified the percentage of NPE cases filed in 2013 as 67%, compared to 64% in 2012, 47% in 2011, 30% in 2010 and 28% in 2009.

PwC refers to the RPX statistics to accentuate that this new study indicates that only 20% ofdecisions in 2013 involved NPE-filed cases, so the general conclusion would be that NPE cases tend to settle or be dismissed prior to a court’s decision. Admittedly, this is indicative of the prevalent “spray and pray” strategy where NPEs prefer to collect many settlement checks from several “targets” and avoid the courtroom.

In this study, who else is an NPE?

If someone were looking to dramatize the role of “trolls,” the name can be thrown around liberally (and hurtfully) to anyone who owns and asserts a patent without offering a product or a service. For instance, colleges and universities fall under the NPE umbrella as their research and development often ends with a series of published papers rather than a marketable product on an assembly line.

In fact, PwC distinguishes universities and non-profits from companies and individuals within their NPE analysis, with only about 5% of the NPE cases from 1995 to 2013 being attributed to universities and non-profits. Almost 50% of the NPE cases are attributed to an “individual,” who could be the listed inventor for the patent or a third-party assignee.

The word “troll” is obviously a derogatory term used to connote greed and hiding (under a bridge), but the term has adopted a newer, meme-like status as trolls are currently depicted as lacking any contribution to society and merely living off of others’ misfortunes and fears. [Three Billy Goats Gruff]. This is not always the truth with NPEs (e.g., universities).

No one wants to be called a troll—especially in front of a jury—so we’ve even recently seen courts bar defendants from referring to NPEs as such colorful terms as a “corporate shell,” “bounty hunter,” “privateer,” or someone “playing the lawsuit lottery.” [Judge Koh Bans Use Of Term ” Patent Troll” In Apple Jury Trial]

Regardless of the portrayal of an NPE, most people in the patent world distinguish the “trolls” by the strength of the patent, merits of the alleged infringement and their behavior upon notification. Often these are expressed as “frivolity” of the case and “gamesmanship” of the attorneys. Courts are able to punish plaintiffs who bring frivolous claims against a party and state bar associations are tasked with monitoring the ethics of attorneys. The USPTO is tasked with working to strengthen the quality of patents.

What’s the take-away from this study regarding NPEs?

The study focuses on patent litigation that produced a decision, therefore the most important and relevant conclusion is that, over the last four years, average damages awards for NPEs are more than triple the damages for practicing entities. Everything else in these articles, such as the initiation of litigation by NPEs, settlement percentages, and the general behavior of patent trolls is pure inference beyond the scope of the study.

This may sound sympathetic to trolls, but keep in mind that the study highlights that NPEs have more than triple the damages on average compared to practicing entities and it is meant to shock the reader a bit. One explanation for this is that NPEs are in the best position to choose the patents they want to assert and choose the targets they wish to sue—especially when the NPE is willing to ride that patent all the way to the end of a long, expensive trial. Sometimes settling is not an option. Chart 2b indicates that the disparity in the damages awarded to NPEs relative to practicing entities has always been big (since 2000), but perhaps going from two-fold from 2000 – 2009 to three times as much in the past 4 years indicates that NPEs are improving at finding patents and/or picking battles to take all the way to a court decision. More than anything, this seems to reflect the growth in the concept of patents as a business asset.

The PwC report is chock full of interesting patterns and trends of litigation results, so it’s a shame that the 67% number makes the headlines—far more interesting are the charts comparing success rates by 4-year periods (Chart 6b) or success rates for NPEs and practicing entities in front of a jury verusin front of a bench (Chart 6c), as well as other tables that reveal statistics for specific districts of the federal courts. Even the stats that look at the success rates of each type of NPE are telling because the reader sees that universities and non-profits have a higher success rate than non-practicing companies or individuals.

What do we do about the trolls?

The White House has recently called for Congress to do something about the trolls as horror stories of scams and shake-downs are shared. A bill was gaining momentum in the Senate, when Senator Leahy took it off the agenda in early July. That bill had miraculously passed 325-91 in the House and President Obama was willing to sign it if the Senate were to pass it. The bill was opposed by trial attorneys, universities, and bio-pharmaceutical businesses who felt as though the law would severely inhibit everyone’s access to the courts in order to hinder just the trolls. Regardless, most people think that the sitting Congressmen merely wanted a “win” prior to the mid-term elections and that patent reform is unlikely to reappear until next term.

In the meantime, the Supreme Court has recently reiterated rules concerning attorney fee-shifting on frivolous patent cases, as well as clarifying the validity of software patents. Time will tell if these changes have any effects on the damages awards that PwC’s study examined or even if they cause a chilling of the number of patent lawsuit filings.

Furthermore, new ways to challenge the validity of asserted patents have been initiated via the America Invents Act. For example, the Inter Partes Review (IPR) has yielded frightening preliminary statistics as to slowing, if not killing, patents that have been asserted in a suit. While these administrative trials are not cheap, many view these new tools at the Patent Trial and Appeals Board as anti-troll measures. It will be interesting to watch how the USPTO implements these procedures in the near future, especially while former Google counsel, Acting Director Michelle K. Lee, oversees the office.

In the private sector, Silicon Valley has recently seen a handful of tech companies come together as the License on Transfer Network, a group hoping to disarm the “Patent Assertion Entities.” Joining the LOT Network comes via an agreement that creates a license for use of a patent by anyone in the LOT network once that patent is sold. The thought is that the NPEs who consider purchasing patents from companies in the LOT Network will have fewer companies to sue since the license to the other active LOT participants will have triggered upon the transfer and, thus, the NPE will not be as inclined to “troll.” For instance, if a member-company such as Google were to sell a patent to a non-member company and an NPE bought that patent, the NPE would not be able to sue any members of the LOT Network with that patent.

Other notes

NPEs are only as evil as the people who run them—that being said, there are plenty of horror stories of small businesses receiving phantom demand letters that threaten a patent infringement suit without identifying themselves or the patent. This is an out-and-out scam and a plague on society that results in wasted time and resource, and inevitably higher prices on the consumer end.

It is a sin and a shame that patent rights can be misused in scams and shake-downs of businesses around us, but there is a reason that U.S. courts are so often used to defend patent rights. The PwC study, at minimum, reflects the high stakes of the patent market and perhaps the fragility. Nevertheless, merely monitoring the courts may not keep the trolls at bay.

I’d love to hear your thoughts.

*This is provided for informational purposes only, and does not constitute legal or financial advice. The information expressed is subject to change at any time and should be checked for completeness, accuracy and current applicability. For advice, consult a suitably licensed attorney or patent agent.

 

III. Large-scale analysis finds majority of clinical trials don’t provide meaningful evidence

Ineffective TreatmentsMedical Ethics • Tags: Center for Drug Evaluation and ResearchClinical trialCTTIDuke University HospitalFDAFood and Drug AdministrationNational Institutes of HealthUnited States National Library of Medicine

04 May 2012

DURHAM, N.C.— The largest comprehensive analysis of ClinicalTrials.gov finds that clinical trials are falling short of producing high-quality evidence needed to guide medical decision-making. The analysis, published today in JAMA, found the majority of clinical trials is small, and there are significant differences among methodical approaches, including randomizing, blinding and the use of data monitoring committees.

“Our analysis raises questions about the best methods for generating evidence, as well as the capacity of the clinical trials enterprise to supply sufficient amounts of high quality evidence to ensure confidence in guideline recommendations,” said Robert Califf, M.D., first author of the paper, vice chancellor for clinical research at Duke University Medical Center, and director of the Duke Translational Medicine Institute.

The analysis was conducted by the Clinical Trials Transformation Initiative (CTTI), a public private partnership founded by the Food and Drug Administration (FDA) and Duke. It extends the usability of the data in ClinicalTrials.gov for research by placing the data through September 27, 2010 into a database structured to facilitate aggregate analysis. This publically accessible database facilitates the assessment of the clinical trials enterprise in a more comprehensive manner than ever before and enables the identification of trends by study type.

 

The National Library of Medicine (NLM), a part of the National Institutes of Health, developed and manages ClinicalTrials.gov. This site maintains a registry of past, current, and planned clinical research studies.

“Since 2007, the Food and Drug Administration Amendment Act has required registration of clinical trials, and the expanded scope and rigor of trial registration policies internationally is producing more complete data from around the world,” stated Deborah Zarin, MD, director, ClinicalTrials.gov, and assistant director for clinical research projects, NLM. “We have amassed over 120,000 registered clinical trials. This rich repository of data has a lot to say about the national and international research portfolio.”

This CTTI project was a collaborative effort by informaticians, statisticians and project managers from NLM, FDA and Duke. CTTI comprises more than 60 member organizations with the goal of identifying practices that will improve the quality and efficiency of clinical trials.

“Since the ClinicalTrials.gov registry contains studies sponsored by multiple entities, including government, industry, foundations and universities, CTTI leaders recognized that it might be a valuable source for benchmarking the state of the clinical trials enterprise,” stated Judith Kramer, MD, executive director of CTTI.

The project goal was to produce an easily accessible database incorporating advances in informatics to permit a detailed characterization of the body of clinical research and facilitate analysis of groups of studies by therapeutic areas, by type of sponsor, by number of participants and by many other parameters.

“Analysis of the entire portfolio will enable the many entities in the clinical trials enterprise to examine their practices in comparison with others,” says Califf. “For example, 96% of clinical trials have ≤1000 participants, and 62% have ≤ 100. While there are many excellent small clinical trials, these studies will not be able to inform patients, doctors and consumers about the choices they must make to prevent and treat disease.”

The analysis showed heterogeneity in median trial size, with cardiovascular trials tending to be twice as large as those in oncology and trials in mental health falling in the middle. It also showed major differences in the use of randomization, blinding, and data monitoring committees, critical issues often used to judge the quality of evidence for medical decisions in clinical practice guidelines and systematic overviews.

“These results reinforce the importance of exploration, analysis and inspection of our clinical trials enterprise,” said Rachel Behrman Sherman, MD, associate director for the Office of Medical Policy at the FDA’s Center for Drug Evaluation and Research. “Generation of this evidence will contribute to our understanding of the number of studies in different phases of research, the therapeutic areas, and ways we can improve data collection about clinical trials, eventually improving the quality of clinical trials.”

Related articles

 

IV.  Lawmakers urge CMS to extend MU hardship exemption for pathologists

 

Eighty-nine members of Congress have asked the Centers for Medicare & Medicaid Services to give pathologists a break and extend the hardship exemption they currently enjoy for all of Stage 3 of the Meaningful Use program.In the letter–dated July 10 and addressed to CMS Administrator Marilyn Tavenner–the lawmakers point out that CMS had recognized in its 2012 final rule implementing Stage 2 of the program that it was difficult for pathologists to meet the Meaningful Use requirements and granted a one year exception for 2015, the first year that penalties will be imposed. They now are asking that the exception be expanded to include the full five-year maximum allowed under the American Recovery and Reinvestment Act.

“Pathologists have limited direct contact with patients and do not operate in EHRs,” the letter states. “Instead, pathologists use sophisticated computerized laboratory information systems (LISs) to support the work of analyzing patient specimens and generating test results. These LISs exchange laboratory and pathology data with EHRs.”

Interestingly, the lawmakers’ exemption request is only on behalf of pathologists, even though CMS had granted the one-year hardship exception to pathologists, radiologists and anesthesiologists.

Rep. Tom Price (R-Ga.), one of the members spearheading the letter, had also introduced a bill (H.R. 1309) in March 2013 that would exclude pathologists from the incentives and penalties of the Meaningful Use program. The bill, which has 31 cosponsors, is currently sitting in committee. That bill also does not include relief for radiologists or anesthesiologists.

CMS has provided some flexibility about the hardship exceptions in the past, most recently by allowing providers to apply for one due to EHR vendor delays in upgrading to Stage 2 of the program.

However, CMS also noted in the 2012 rule granting the one-year exception that it was granting the exception in large part because of the then-current lack of health information exchange and that “physicians in these three specialties should not expect that this exception will continue indefinitely, nor should they expect that we will grant the exception for the full 5-year period permitted by statute.”

To learn more:
– read the letter (.pdf)

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