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Posts Tagged ‘European Union’


Real Time Coverage @BIOConvention #BIO2019: Genome Editing and Regulatory Harmonization: Progress and Challenges

Reporter: Stephen J Williams, PhD @StephenJWillia2

 

Genome editing offers the potential of new and effective treatments for genetic diseases. As companies work to develop these treatments, regulators are focused on ensuring that any such products meet applicable safety and efficacy requirements. This panel will discuss how European Union and United States regulators are approaching therapeutic use of genome editing, issues in harmonization between these two – and other – jurisdictions, challenges faced by industry as regulatory positions evolve, and steps that organizations and companies can take to facilitate approval and continued efforts at harmonization.

 

CBER:  because of the nature of these gene therapies, which are mainly orphan, there is expedited review.  Since they started this division in 2015, they have received over 1500 applications.

Spark: Most of the issues were issues with the primary disease not the gene therapy so they had to make new endpoint tests so had talks with FDA before they entered phase III.   There has been great collaboration with FDA,  now they partnered with Novartis to get approval outside US.  You should be willing to partner with EU pharmas to expedite the regulatory process outside US.  In China the process is new and Brazil is behind on their gene therapy guidance.  However there is the new issue of repeat testing of your manufacturing process, as manufacturing of gene therapies had been small scale before. However he notes that problems with expedited review is tough because you don’t have alot of time to get data together.  They were lucky that they had already done a randomized trial.

Sidley Austin:  EU regulatory you make application with advance therapy you don’t have a national option, the regulation body assesses a committee to see if has applicability. Then it goes to a safety committee.  EU has been quicker to approve these advance therapies. Twenty five percent of their applications are gene therapies.  Companies having issues with manufacturing.  There can be issues when the final application is formalized after discussions as problems may arise between discussions, preliminary applications, and final applications.

Sarepta: They have a robust gene therapy program.  Their lead is a therapy for DMD (Duchenne’s Muscular Dystrophy) where affected males die by 25. Japan and EU have different regulatory applications and although they are similar and data can be transferred there is more paperwork required by EU.  The US uses an IND for application. Global feedback is very challenging, they have had multiple meetings around the world and takes a long time preparing a briefing package….. putting a strain on the small biotechs.  No company wants to be either just EU centric or US centric they just want to get out to market as fast as possible.

 

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1:15PM 11/12/2014 – 10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston

REAL TIME Coverage of this Conference by Dr. Aviva Lev-Ari, PhD, RN – Director and Founder of LEADERS in PHARMACEUTICAL BUSINESS INTELLIGENCE, Boston http://pharmaceuticalintelligence.com

1:15 p.m. – Keynote Speaker – International Genetics Health and Disease

International Genetics Health and Disease

The principles of personalized medicine and how they affect the lives of people acknowledge no national boundaries. Although there are some differences among the diverse populations around the world in terms of their genetic variation, the general principles of personalized medicine apply uniformly across many populations. Dr. Periz will discuss how personalized medicine is viewed across the many European countries with particular emphasis on how Spain is implementing it into its medical care.

Keynote Speaker

Antonio L. Andreu Periz, M.D.
Director, Instituto de Salud Carlos III, Madrid

@insalud_es  @CIBER-BBN

Governmental & Public Health National Organization like a combination of CDC and “Hybrid NIH in the US”

Personalized Medicine (PM) in Europe

Europe and Spain — PM is changing Medical Practice, regulations standard of care.

 

In Europe 28 National systems in Spain alone 17 systems

Implementation of PM in Europe: Hospitals, Regulation,

  • develop proof of concept
  • identify mechanisms
  • bring basic research to clinical
  • incorporation into a Portfolio of policies on PM

Horizon 2020 in EU – 2016 launch action on PM in various countries in EU

  • Translational level for all EC members
  • Coalition of 28 Research Centers in Europe to promote PM
  • Sharing Databases, Data on HC, infrastructure for Translational research
  • OMICS
  • Biomarkers
  • clinical trials

CSA – Coordination Support Action

  • PerMed 500,000 Euro for 5 years, 9 operating partners, representatives of Ministry of Health, Israel and Canada Ministry of Health are included
  • Research Agenda for PM in Europe – SWOT Analysis
  • Recommendations for UC to start PM in 2016
  • – basic research
  • – translation
  • – ICTs
  • – Regulatory

SPAIN – Initiatives on PM: Aggregation of Knowledge

  • One single organization collaborates with 22 Institutions on Biomedical research – Concentration in Barcelona and in Madrid
  • Projects of Excellence: PhD level Projects – Clinical Practice: Imaging, Endocrinology, genomics, cardiology
  • 2014 — 35 Applicants – not all are on Cancer 25% are in Cancer 75% are in other clinical Fields
  • 12Million Euros will fund 1/4 of the applicants
  • PhD Thesis on PM – common project 2 yr governmental institute and 2 years in biotech industry

EAPM – Europe Alliance for PM

  • raise awareness on HOW PM CAN SHAPE Healthcare in Europe: Diagnosis, Treatment,
  • Specialized Treatment for Europe’s Patient (STEPs) – Five Steps

Global alliances to shape Medical Practice based on PM – Collaboration Industry and Academia

  • PMC in the US (Personalized Medical Coalition)
  • PerMEd in Europe (coalition  in Europe  supporting innovation in personalized medicine)
  • EAPM (European Alliance for Personalized Medicine)

 

 

– See more at: http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx#sthash.qGbGZXXf.dpuf

@HarvardPMConf

#PMConf

@SachsAssociates

@insalud_es

@CIBER-BBN

@EIGlobalNet

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UPDATED: PLATO Trial on ACS: BRILINTA (ticagrelor) better than Plavix® (clopidogrel bisulfate): Lowering chances of having another heart attack

Reporter: Aviva Lev-Ari, PhD, RN

 

UPDATED on 9/1/2019

Extended DAPT with Brilinta: No Benefit for Stable CAD in T2D

Substudy in those with prior PCI might identify group where bleeding tradeoff is worthwhile

PARIS — Ticagrelor (Brilinta) as part of a dual antiplatelet therapy (DAPT) regimen didn’t improve net outcomes for stable coronary artery disease (CAD) among type 2 diabetes patients, except perhaps in the setting of percutaneous coronary intervention (PCI), the THEMIS trial showed.

Adding the potent antiplatelet agent to aspirin reduced cardiovascular (CV) death, myocardial infarction (MI), or stroke (7.7% vs 8.5%, HR 0.90, 95% CI 0.81-0.99), reported Deepak Bhatt, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, at the European Society of Cardiology (ESC) congress and online in the New England Journal of Medicine.

But it also increased

  • TIMI major bleeding (2.2% vs 1.0%, HR 2.32, 95% CI 1.82-2.94) and
  • intracranial hemorrhage (0.7% vs 0.5%, HR 1.71, 95% CI 1.18- 2.48) over aspirin alone, albeit
  • without more fatal bleeding (0.2% vs 0.1%, P=0.11).

The combined effect was neutral for the exploratory composite outcome of “irreversible harm” (death from any cause, MI, stroke, fatal bleeding, or intracranial hemorrhage 10.1% vs 10.8%, HR 0.93, 95% CI 0.86-1.02).

ESC session study discussant Colin Baigent, MD, of Oxford University in England, actually calculated 12 major bleeds for every eight events prevented.

“This is a consistent story: when we add an antiplatelet agent for risk reduction, we increase the risk of bleeding,” noted Richard Kovacs, MD, of Indiana University in Indianapolis and president of the American College of Cardiology.

THEMIS is the final part of a largely-disappointing PARTHENON development program for ticagrelor, he noted. “It hasn’t changed practice. …Will the main THEMIS trial change clinical practice? In my opinion, no.”

SOURCE

https://www.medpagetoday.com/meetingcoverage/esc/81925?xid=nl_mpt_ACC_Reporter_2019-09-01&eun=g5099207d2r

 

UPDATED on 10/4/2016

Soriot’s $3.5B Brilinta dream is dashed by yet another big trial flop for AstraZeneca

by john carroll
October 4, 2016 09:00 AM EDT
Updated: 09:33 AM

Brilinta, the drug failed to demonstrate a benefit over generic Plavix (clopidogrel) for peripheral artery disease. Back in March, the heart drug flopped in a large stroke study, unable to prove that it could beat aspirin. And Soriot can chalk up those expensive studies to proving Brilinta’s serious deficiencies.

“We don’t believe the goal of $3.5 billion is attainable. I think it would be unrealistic to believe that,” Ludovic Helfgott, head of AstraZeneca’s Brilinta business, told Reuters.

Brilinta brought in a total of $619 million last year after disappointing analysts repeatedly with lower-than-expected quarterly revenue.

Heart studies aren’t cheap. AstraZeneca recruited 13,500 patients for the EUCLID study, and it had enrolled close to that number for the earlier SOCRATES trial.

SOURCE

http://endpts.com/soriots-3-5b-brilinta-dream-is-dashed-by-yet-another-big-trial-flop-for-astrazeneca/?utm_medium=email&utm_campaign=75%20Dinner%20with%20Brent&utm_content=75%20Dinner%20with%20Brent+CID_8008d3b4f16d90576238cceef624d211&utm_source=ENDPOINTS%20emails&utm_term=Soriots%2035B%20Brilinta%20dream%20is%20dashed%20by%20yet%20another%20big%20trial%20flop%20for%20AstraZeneca

UPDATED on 9/4/2014

Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction

Gilles Montalescot, M.D., Ph.D., Arnoud W. van ‘t Hof, M.D., Ph.D., Frédéric Lapostolle, M.D., Ph.D., Johanne Silvain, M.D., Ph.D., Jens Flensted Lassen, M.D., Ph.D., Leonardo Bolognese, M.D., Warren J. Cantor, M.D., Ángel Cequier, M.D., Ph.D., Mohamed Chettibi, M.D., Ph.D., Shaun G. Goodman, M.D., Christopher J. Hammett, M.B., Ch.B., M.D., Kurt Huber, M.D., Magnus Janzon, M.D., Ph.D., Béla Merkely, M.D., Ph.D., Robert F. Storey, M.D., D.M., Uwe Zeymer, M.D., Olivier Stibbe, M.D., Patrick Ecollan, M.D., Wim M.J.M. Heutz, M.D., Eva Swahn, M.D., Ph.D., Jean-Philippe Collet, M.D., Ph.D., Frank F. Willems, M.D., Ph.D., Caroline Baradat, M.Sc., Muriel Licour, M.Sc., Anne Tsatsaris, M.D., Eric Vicaut, M.D., Ph.D., and Christian W. Hamm, M.D., Ph.D. for the ATLANTIC Investigators

September 1, 2014DOI: 10.1056/NEJMoa1407024

BACKGROUND

The direct-acting platelet P2Y12 receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown.

METHODS

We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours’ duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days.

RESULTS

The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used.

CONCLUSIONS

Prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. (Funded by AstraZeneca; ATLANTIC ClinicalTrials.gov number, NCT01347580.)

SOURCE

http://www.nejm.org/doi/full/10.1056/NEJMoa1407024?query=TOC

 

 

UPDATED on 2/7/2014

PLATO Controversy Hits the Wall Street Journal

February 05, 2014

NEW YORK, NY – The controversy surrounding the PLATOtrial of ticagrelor (Brilinta, AstraZeneca) continues unabated, according to a story published in the Wall Street Journal. Specifically, a sealed complaint filed in US district court in the District of Columbia by a researcher contends that the cardiovascular events in the study “may have been manipulated” [1].

Dr Victor Serebruany (HeartDrug Research Laboratories, Johns Hopkins University, Towson, MD), who has long been a thorn in the side of AstraZeneca and the PLATO investigators, filed the complaint under the False Claims Act, reports theWall Street Journal. The Journal notes that the US attorney’s office in Washington, DC, has contacted Serebruany and is currently investigating the clinical trial.As reported by heartwirein October 2013, the US Department of Justice issued a civil investigative demand from its civil division “seeking documents and information regarding PLATO.” AstraZeneca is complying with the request.

First reported by heart wirein 2009 , the PLATO trial was a positive study involving more 18 000 patients from 43 countries. PLATO investigators, led by Dr Lars Wallentin (Uppsala Clinical Research Center, Sweden), showed that treating acute coronary syndrome patients with ticagrelor significantly reduced the rate of MI, stroke, and cardiovascular death compared with patients taking clopidogrel. Results were presented at the European Society of Cardiology 2009 Congress and reported in the New England Journal of Medicine.

PLATO has been dogged by questions, including prior to approval. In the sealed complaint, Serebruany takes issue with a number of things, many of which have been reported previously. He alleges that the

  • number of clinical events among those taking clopidogrel was high compared with other studies, pointing out that the rate of all-cause death was 5.9% among clopidogrel-treated patients—nearly twice as high as earlier studies. In addition,
  • the sealed complaint documents the geographic discrepancies in the trial, noting there was a trend toward worse outcomes with ticagrelor at North American sites.The complaint also alleges that
  • an initial count of clinical events suggested the two drugs were equivalent, but adjudication by the Duke Clinical Research Institute attributed another 45 MIs to the clopidogrel group, which tipped the results in favor of ticagrelor. Other questions raised about the study include
  • site monitoring and timing of clinical events. Serebruany also alleges that
  • the trial may have unintentionally been unblinded because of the shape of clopidogrel’s “split capsules,” which would have enabled doctors and nurses to know which drug patients received.

AstraZeneca rebutted these issues, telling the Journal that it is cooperating with the government. It said it is confident in the integrity of the trial and noted the overall study showed the superiority of ticagrelor over clopidogrel. There is no evidence the trial was unblinded and researchers used the same standards when qualifying all clinical events, including MIs, they noted. In addition, the company said it is not possible to compare event rates with clopidogrel in PLATO with other studies because the patient populations differ.

The Journal reports that Serebruany became embroiled in the controversy when asked by the FDA‘s Dr Thomas Marciniak to advise the agency about the PLATO data in 2010. Marciniak, who led the FDA’s review of PLATO, called AstraZeneca’s submission on serious adverse events the “worst submission” he ever encountered. According to the submission, he noted, 12 patients reported their own deaths by telephone. Before approving ticagrelor, the FDA requested an additional analysis of PLATO, and it was eventually approved in the US in July 2011. Ticagrelor was approved in Europe in December 2010 and is authorized for use in more than 100 countries.

The Journal called Serebruany an expert in the antiplatelet field but said he is a “controversial figure,” partly because of his financial ties to industry and repeated criticisms of new drug approvals. Through HeartDrug Research, Serebruany has worked on prasugrel (Effient, Lily/Daiichi-Sankyo), a competing antiplatelet agent, but has also done work for AstraZeneca.

REFERENCE

Burton TM. Doctor challenges testing of AstraZeneca’s Brilinta. Wall Street Journal, February 2, 2014. Available here.

SOURCE

http://www.medscape.com/viewarticle/820236?nlid=47583_1984&src=wnl_edit_medn_card&uac=93761AJ&spon=2

UPDATED 3/28/2013

How AstraZeneca Will Use A Diagnostic To Market Its Blood Thinner

by Matthew Harper, Forbes Staff on 3/21/2013

Earlier today I wrote about how AstraZeneca is telling investors that its blood-thinner Brilinta, used to prevent second heart attacks, could be a multi-billion dollar drug, at least twice as big as Wall Street analysts expect. So far the drug has been a disappointment.

I wrote:

Another key data point Astra presented was that blood levels of troponin, a muscle protein released by the heart during a heart attack, predict which patients get the most benefit from Brilinta. This data is not in AstraZeneca’s label, but a spokeswoman said that she believed it would be something the company can market to doctors.

via Can Pascal Soriot Turn Around AstraZeneca? It May Come Down To One Drug – Forbes.

But will the Food and Drug Administration allow Astra to tell doctors that? Stratification using troponin is not in Brilinta’s FDA-approved label, and off-label promotion is illegal. But Ferguson says that communications about troponin will be allowed because all patients with high troponin are patients who would be included in the FDA-approved indication. He confirms that use of troponin testing will be part of the new marketing plan for Brilinta.

SOURCE:

http://www.forbes.com/sites/matthewherper/2013/03/21/how-astrazeneca-will-use-a-diagnostic-to-market-its-blood-thinner/

Can Pascal Soriot Turn Around AstraZeneca? It May Come Down To One Drug

by Matthew Herper, Forbes Staff on 3/21/2013

This morning in New York, new AstraZeneca chief executive Pascal Soriot is telling investors how he is going to turn around the company that has had the absolute worst track record in research and development among any big pharmaceutical firm. The plan is fairly wide-ranging and involves a lot of the steps one might expect:

  • new layoffs (2,300 jobs);
  • a re-focusing of research and development on three areas: heart disease and diabetes; oncology; and respiratory and inflammation;
  • new R&D initiatives involving Moderna, a biotech company, and the Karolinska Instutet;
  • moving the company’s headquarters to its R&D hub in Cambridge, U.K.;
  • re-focusing on emerging markets, where AZ already gets $6 billion in sales, especially China.

But the short-term key to delivering on his promises today seems to come down to a single drug: Brilinta, the Plavix competitor thatAstraZeneca introduced in 2011 which has so far disappointed, generating  just $324 $89 million in global sales last year. This is a medicine to prevent heart attacks and strokes in patients who suffer acute coronary syndrome, the condition that occurs after a heart attack or serious heart-related chest pain. It works by preventing the formation of blood clots.

Plavix was the second biggest drug in the world, with $6 billion in annual sales, but it is now generic. The conventional wisdom is that it will be difficult to compete with cheap generics. Brilinta is actually trailing Effient, a similar medicine from Eli Lilly, in usage. Wall Street consensus currently sees Brilinta growing to become a moderate-sized drug in 2018, with $1.3 billion in annual sales. But AstraZeneca is saying that it thinks Brilinta can be a multi-billion dollar product. Astra has confirmed that this means Brilinta will have to surpass Effient. The newer drugs also cause more bleeding than Plavix.

What is the company’s argument? In his presentation today, Paul Hudson, Astra’s Executive Vice President, North America, said that the key would be focusing on one key fact: Brilinta reduced cardiovascular deaths by 21% compared to Plavix in a big clinical trial. That would mean that if everyone eligible for Brilinta got it, 100,000 lives would be saved.

But the reality is that doctors have been skeptical of that data because in the part of that trial that was run in North America, the benefit was less clear. AstraZeneca says that this may have been due to an interaction of Brilinta and aspirin and that, according to current cardiovascular guidelines, doctors should be prescribing less aspirin anyway.

Another key data point Astra presented was that blood levels of troponin, a muscle protein released by the heart during a heart attack, predict which patients get the most benefit from Brilinta. This data is not in AstraZeneca’s label, but a spokeswoman said that she believed it would be something the company can market to doctors.

A lot of what Astra will do in the short term on Brilinta will be blocking and tackling. It needs to pay bigger rebates to insurers to make sure that patients can get cheap access to the drug. (This is how discounts happen in the American insurance system: the patient pays a co-payment and the insurer pays full price for the drug, but then the drug maker gives the insurer money back to make the end cost cheaper.) It will also be doing a lot of medical marketing, involving its internal experts or paid, external doctors, to get the word out about the benefits of Brilinta.

Brilinta has other advantages (it stops acting quickly) and disadvantages (it must be given twice a day). But the other big question for expanding results is whether large clinical trials that are now ongoing will show that it works in a broader array of heart patients. Astra is starting a big trial to show Brilinta prevents strokes. These trials are risky and expensive, but there will be a big payoff if they work.

Astra has some other commercial levers to point to. It’s diabetes pill Onglyza, which is sold with Bristol-Myers Squibb, will have results in a big study of its efficacy in preventing heart disease before a similar study of Merck’s top-selling Januvia, which started first. Soriot has smart ideas about which drugs to advance into later testing. But Brilinta is going to be the biggest single indicator of whether Soriot’s new strategies are paying off.

SOURCE:

http://www.forbes.com/sites/matthewherper/2013/03/21/can-pascal-soriot-turn-around-astrazeneca-it-may-come-down-to-one-drug/

BRILINTA is an antiplatelet medication

Taking BRILINTA is a first step in the treatment your physician has chosen for you. At BRILINTA.com, you will find helpful information and useful learning tools to help you complete your course of BRILINTA therapy. Make sure you and your loved ones read through all of the sections.

What is BRILINTA?

BRILINTA is a type of prescription antiplatelet medication for people who have had a recent heart attack or severe chest pain that happened because their heart wasn’t getting enough oxygen and who are being treated with medicines or procedures to open blocked arteries in the heart. BRILINTA is used with aspirin to stop platelets from sticking together and forming a blood clot that could block blood flow to the heart and cause another, possibly fatal, heart attack. Platelets are small cells in the blood that help with normal blood clotting.

Take BRILINTA and aspirin exactly as instructed by your doctor: BRILINTA twice a day, plus one 81-mg aspirin tablet once a day. You should not take a dose of aspirin higher than 100 mg each day because it can affect how well BRILINTA works. Tell your doctor about any medicines you are taking that contain aspirin. Do not take any new medicines that contain aspirin.

Why BRILINTA?

BRILINTA used with aspirin lowers your chance of having another serious problem with your heart or blood vessels such as heart attack, stroke, or blood clots in your stent if you received one. These can be fatal. In fact, in a large clinical study BRILINTA was even better than Plavix® (clopidogrel bisulfate) tablets at lowering your chances of having another heart attack.

BRILINTA is used to lower your chance of having another heart attack or dying from a heart attack, but BRILINTA (and similar drugs) can cause bleeding that can be serious and sometimes lead to death.

Complete the
Course
 Program

IMPORTANT SAFETY INFORMATION ABOUT BRILINTA

BRILINTA is used to lower your chance of having another heart attack or dying from a heart attack or stroke, but BRILINTA (and similar drugs) can cause bleeding that can be serious and sometimes lead to death. Instances of serious bleeding, such as internal bleeding, may require blood transfusions or surgery. While you take BRILINTA, you may bruise and bleed more easily and be more likely to have nosebleeds. Bleeding will also take longer than usual to stop.

Call your doctor right away if you have any signs or symptoms of bleeding while taking BRILINTA, including: severe, uncontrollable bleeding; pink, red, or brown urine; vomit that is bloody or looks like coffee grounds; red or black stool; or if you cough up blood or blood clots.

Do not stop taking BRILINTA without talking to the doctor who prescribes it for you. People who are treated with a stent, and stop taking BRILINTA too soon, have a higher risk of getting a blood clot in the stent, having a heart attack, or dying. If you stop BRILINTA because of bleeding, or for other reasons, your risk of a heart attack or stroke may increase. Tell all your doctors and dentists that you are taking BRILINTA. To decrease your risk of bleeding, your doctor may instruct you to stop taking BRILINTA 5 days before you have elective surgery. Your doctor should tell you when to start taking BRILINTA again, as soon as possible after surgery.

Take BRILINTA and aspirin exactly as instructed by your doctor. You should not take a dose of aspirin higher than 100 mg daily because it can affect how well BRILINTA works. Tell your doctor if you take other medicines that contain aspirin. Do not take new medicines that contain aspirin.

Do not take BRILINTA if you are bleeding now, especially from your stomach or intestine (ulcer), have a history of bleeding in the brain, or have severe liver problems.

BRILINTA can cause serious side effects, including bleeding and shortness of breath. Call your doctor if you have new or unexpected shortness of breath or any side effect that bothers you or that does not go away. Your doctor can decide what treatment is needed.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. BRILINTA may affect the way other medicines work, and other medicines may affect how BRILINTA works.

Approved uses
BRILINTA is a prescription medicine for people who have had a recent heart attack or severe chest pain that happened because their heart wasn’t getting enough oxygen and who are being treated with medicines or procedures to open blocked arteries in the heart.

BRILINTA is used with aspirin to lower your chance of having another serious problem with your heart or blood vessels such as heart attack, stroke, or blood clots in your stent if you received one. These can be fatal.

Please read Prescribing Information, including Boxed WARNINGS.

Please read Medication Guide.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

If you are without prescription coverage and cannot afford your medication, AstraZeneca may be able to help. For more information, please visit www.AstraZeneca.com.

This product information is intended for US consumers only.

BRILINTA is a trademark of the AstraZeneca group of companies.

Plavix® is a registered trademark of sanofi-aventis.

©2012 AstraZeneca.706809-1789005 8/12

SOURCE:

http://www.brilinta.com/antiplatelet-prescription-medication.aspx#au

http://www1.astrazeneca-us.com/pi/brilinta.pdf

BRILINTA (ticagrelor)

Ticagrelor (trade name Brilinta in the US, Brilique and Possia in the EU) is a platelet aggregation inhibitor produced by AstraZeneca. The drug was approved for use in the European Union by the European Commission on December 3, 2010.[1][2] The drug was approved by the US Food and Drug Administrationon July 20, 2011.[3]

Indications

Ticagrelor is indicated for the prevention of thrombotic events (for example stroke or heart attack) in patients with acute coronary syndrome or myocardial infarction with ST elevation. The drug is combined with acetylsalicylic acid unless the latter is contraindicated.[4] Treatment of acute coronary syndrome with ticagrelor as compared with clopidogrel significantly reduces the rate of death.[5]

Contraindications

Contraindications for ticagrelor are: active pathological bleeding and a history of intracranial bleeding, as well as reduced liver function and combination with drugs that strongly influence activity of the liver enzymeCYP3A4, because the drug is metabolized via CYP3A4 and excreted via the liver.[4]

Adverse effects

The most common side effects are shortness of breath (dyspnea, 14%)[6] and various types of bleeding, such as hematomanosebleedgastrointestinalsubcutaneous or dermal bleeding. Allergic skin reactions such as rash and itching have been observed in less than 1% of patients.[4]

Physical and chemical properties

Ticagrelor is a nucleoside analogue: the cyclopentane ring is similar to the sugar ribose, and the nitrogen rich aromatic ring system resembles the nucleobase purine, giving the molecule an overall similarity toadenosine. The substance has low solubility and low permeability under the Biopharmaceutics Classification System.[1]

Ticagrelor as a nucleoside analogue

The nucleoside adenosinefor comparison

Pharmacokinetics

Ticagrelor is absorbed quickly from the gut, the bioavailability being 36%, and reaches its peak concentration after about 1.5 hours. The main metabolite, AR-C124910XX, is formed quickly via CYP3A4 by de-hydroxyethylation at position 5 of the cyclopentane ring.[7] It peaks after about 2.5 hours. Both ticagrelor and AR-C124910XX are bound to plasma proteins (>99.7%), and both are pharmacologically active. Blood plasma concentrations are linearly dependent on the dose up to 1260 mg (the sevenfold daily dose). The metabolite reaches 30–40% of ticagrelor’s plasma concentrations. Drug and metabolite are mainly excreted via bile and feces.

Plasma concentrations of ticagrelor are slightly increased (12–23%) in elderly patients, women, patients of Asian ethnicity, and patients with mild hepatic impairment. They are decreased in patients that described themselves as ‘coloured’ and such with severe renal impairment. These differences are considered clinically irrelevant. In Japanese people, concentrations are 40% higher than in Caucasians, or 20% after body weight correction. The drug has not been tested in patients with severe hepatic impairment.[4]

Mechanism of action

Like the thienopyridines prasugrelclopidogrel and ticlopidine, ticagrelor blocks adenosine diphosphate (ADP) receptors of subtype P2Y12. In contrast to the other antiplatelet drugs, ticagrelor has a binding site different from ADP, making it an allosteric antagonist, and the blockage is reversible.[8] Moreover, the drug does not need hepatic activation, which might work better for patients with genetic variants regarding the enzyme CYP2C19 (although it is not certain whether clopidogrel is significantly influenced by such variants).[9][10][11]

Comparison with clopidogrel

The PLATO trial, funded by AstraZeneca, in mid-2009 found that ticagrelor had better mortality rates than clopidogrel (9.8% vs. 11.7%, p<0.001) in treating patients with acute coronary syndrome. Patients given ticagrelor were less likely to die from vascular causes, heart attack, or stroke but had greater chances of non-lethal bleeding (16.1% vs. 14.6%, p=0.0084), higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding. Rates of major bleeding were not different. Discontinuation of the study drug due to adverse events occurred more frequently with ticagrelor than with clopidogrel (in 7.4% of patients vs. 6.0%, P<0.001)[5] The PLATO trial showed a statistically insignificant trend toward worse outcomes with ticagrelor versus clopidogrel among US patients in the study – who comprised 1800 of the total 18,624 patients. The HR actually reversed for the composite end point cardiovascular (death, MI, or stroke): 12.6% for patients given ticagrelor and 10.1% for patients given clopidogrel (HR = 1.27). Some believe the results could be due to differences in aspirin maintenance doses, which are higher in the United States.[12] Others state that the central adjudicating committees found an extra 45 MIs in the clopidogrel (comparator) arm but none in the ticagrelor arm, which improved the MI outcomes with ticagrelor. Without this adjudication the trials’ primary efficacy outcomes should not be significant[13]

Consistently with its reversible mode of action, ticagrelor is known to act faster and shorter than clopidogrel.[14] This means it has to be taken twice instead of once a day which is a disadvantage in respect of compliance, but its effects are more quickly reversible which can be useful before surgery or if side effects occur.[4][15]

Interactions

Inhibitors of the liver enzyme CYP3A4, such as ketoconazole and possibly grapefruit juice, increase blood plasma levels and consequently can lead to bleeding and other adverse effects. Conversely, drugs that are metabolized by CYP3A4, for example simvastatin, show increased plasma levels and more side effects if combined with ticagrelor. CYP3A4 inductors, for example rifampicin and possibly St. John’s wort, can reduce the effectiveness of ticagrelor. There is no evidence for interactions via CYP2C9.

The drug also inhibits P-glycoprotein (P-gp), leading to increased plasma levels of digoxinciclosporin and other P-gp substrates. Ticagrelor and AR-C124910XX levels are not significantly influenced by P-gp inhibitors.[4]

In the US a boxed warning states that use of ticagrelor with aspirin doses exceeding 100 mg/day decreases the effectiveness of the medication.[16]

References

  1. a b “Assessment Report for Brilique”European Medicines Agency. January 2011.
  2. ^ European Public Assessment Report Possia
  3. ^ “FDA approves blood-thinning drug Brilinta to treat acute coronary syndromes”. FDA. 20 July 2011.
  4. a b c d e f Haberfeld, H, ed. (2010) (in German). Austria-Codex (2010/2011 ed.). Vienna: Österreichischer Apothekerverlag.
  5. a b Wallentin, Lars; Becker, RC; Budaj, A; Cannon, CP; Emanuelsson, H; Held, C; Horrow, J; Husted, S et al. (August 30, 2009). “Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes”NEJM 361 (11): 1045–57. doi:10.1056/NEJMoa0904327PMID 19717846.
  6. ^ Brilinta: Highlights of prescribing information
  7. ^ Teng, R; Oliver, S; Hayes, MA; Butler, K (2010). “Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects”. Drug metabolism and disposition: the biological fate of chemicals 38 (9): 1514–21. doi:10.1124/dmd.110.032250PMID 20551239.
  8. ^ Birkeland, Kade; Parra, David; Rosenstein, Robert (2010). “Antiplatelet therapy in acute coronary syndromes: focus on ticagrelor”Journal of Blood Medicine 1: 197–219.
  9. ^ H. Spreitzer (February 4, 2008). “Neue Wirkstoffe – AZD6140” (in German). Österreichische Apothekerzeitung (3/2008): 135.
  10. ^ Owen, RT, Serradell, N, Bolos, J (2007). “AZD6140”. Drugs of the Future 32 (10): 845–853. doi:10.1358/dof.2007.032.10.1133832.
  11. ^ Tantry, Udaya S; Bliden, Kevin P (2010). “First Analysis of the Relation Between CYP2C19 Genotype and Pharmacodynamics in Patients Treated With Ticagrelor Versus Clopidogrel”. Circulation: Cardiovascular Genetics 3: 556–566. doi:10.1161/CIRCGENETICS.110.958561.
  12. ^ Bernardo Lombo, José G Díez. Ticagrelor: the evidence for its clinical potential as an oral antiplatelet treatment for the reduction of major adverse cardiac events in patients with acute coronary syndromes Core Evid. 2011; 6: 31–42. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065559/
  13. ^ Serebruany VL, Atar D. Viewpoint: Central adjudication of myocardial infarction in outcome-driven clinical trials—Common patterns in TRITON, RECORD, and PLATO? Thromb Haemost 2012; DOI: 10.1160/TH12-04-0251. http://www.theheart.org/article/1433145/print.do
  14. ^ Miller, R (24 February 2010). “Is there too much excitement for ticagrelor?”. TheHeart.org.
  15. ^ H. Spreitzer (17 January 2011). “Neue Wirkstoffe – Elinogrel” (in German). Österreichische Apothekerzeitung (2/2011): 10.
  16. ^ July 20, 2011 AstraZeneca: Ticagrelor (Brilinta) Gains FDA Approval Larry Husten cardiobrief.org/2011/07/20/astrazeneca-ticagrelor-brilinta-gains-fda-approval/

SOURCE:

 http://en.wikipedia.org/wiki/Ticagrelor

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Reporter: Aviva Lev-Ari, PhD, RN

With $15.5M Grant, EU Consortium to Sequence 1,100 Exomes to Develop Diagnostics for Neurologic Diseases

November 28, 2012

A consortium of 18 European and Australian institutions and industry partners will spend five years sequencing the exomes of 1,100 patients with neurodegenerative and neuromuscular diseases to create diagnostic panels and uncover novel therapeutic targets.

The group, known as the Neuromics Consortium, is funded with €12 million ($15.5 million) under the European Union’s seventh framework program.

Headed by the University of Tübingen, the project will involve collaboration between 12 academic centers. Iceland’s Decode Genetics will do the sequencing and will support analysis and return of results to participants. The group also plans to work with Agilent Technologies to develop and validate targeted sequencing-based diagnostic panels for specific neurologic diseases, including ataxia/paraplegias, spinal muscular atrophies and lower motor neuron diseases, and neuromuscular diseases, according to Tübingen’s Holm Graessner, the manager of the consortium.

Graessner told Clinical Sequencing News in an email that the Neuromics Consortium hopes its work will yield better diagnostic panels that can increase the diagnosis rate for ten main neurodegenerative and neuromuscular disease types — including ataxia, spastic paraplegia, Huntington’s disease, muscular dystrophy and spinal muscular atrophy — as well as provide information on genes and pathways that could inform new treatments.

According to the consortium, 30 percent to 80 percent of patients with these diseases are still undiagnosed by current single-gene tests or gene panels, and cohorts for each individual disorder are small. By combining patient groups and data from many centers and looking for commonality between some of these diseases, the consortium hopes to create diagnostics that cover a greater range of causative mutations.

While each specific disorder the group will study is relatively rare, many have overlapping manifestations, which suggest similarities in disease pathways pointing to common therapeutic strategies, according to the group.

Graessner said that the project’s whole-exome sequencing component will take place mostly in the first two years. According to the consortium’s plan, Decode Genetics — which expanded last year from array-based SNP genotyping research to a next-gen sequencing approach (CSN 11/9/2011) — will use its Illumina HiSeqs to sequence at least 1,100 subjects. The group expects this to increase the percentage of disease genes known for some of the more heterogeneous diseases in the set from about 50 percent to 80 percent.

According to Graessner, RNA sequencing is also part of the plan, as well as proteomic and other ‘omic analyses, especially as the researchers move from sequencing toward diagnostic panel development and therapeutic target research.

“We plan to [do whole-exome sequencing for] 1,100 subjects for gene identification … equally distributed over 10 disease areas,” Graessner wrote. “[This] will be done mainly in the first two years. However, for some of the diseases, such as ataxia/paraplegias, we have diagnostic panels already and in that case we [will] do the panels first and send the still unclear families for WES or WGS,” he wrote.

Graessner said that the group is just now shipping its first sample package to Decode. When this is finished the group will hold a workshop to discuss and train all the participating academic centers in the use of the Decode database for analysis of the results.

He said the team plans to work with the Halo Genomics division of Agilent, to validate diagnostic panels for ataxia, spinal muscular atrophies, lower motor neuron disease, and neuromuscular diseases. Halo was acquired by Agilent last year, and had developed an enrichment technology dubbed HaloPlex that it said was especially suited for targeted gene panels less than one megabase in size (IS 12/6/2011).

The group’s bioinformatics partner, Ariadne Genomics, will also analyze data to support the diagnostics research, as well as research on potential novel therapeutic targets, according to Graessner.

In a document describing the project, the consortium wrote that at the end of the funding period, it expects “to have elucidated the genetic basis for [more than] 80 [percent] of investigated patient groups.”

According to the group, the new genes will be added to existing databases and used to develop the first overlapping gene panel that can be used to diagnose several of these individual diseases, “overcoming time consuming and costly single gene analysis.”

Molika Ashford is a GenomeWeb contributing editor and covers personalized medicine and molecular diagnostics. E-mail her here.

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Curated and Reported by: Dr. Venkat S. Karra, Ph.D.

Know How We ALL Knowingly or Unknowingly Consume Antibiotics and How it Effects Our Health

Billions of microbial cells live in the guts of humans and other animals. Research on these vast bacterial populations, called microbiomes, is just getting started, but scientists already know that some microbial boarders play a crucial role in breaking down nutrients in our diet. Some have also suspected that low-dose antibiotics, given to farm animals to make them grow bigger, could work by altering the gut microbiome.

To test this hypothesis, a team led by microbiologist Martin Blaser of the New York University School of Medicine in New York City added antibiotics to the drinking water of mice that had just been weaned. The medicine—either penicillin, vancomycin, a combination of the two, or chlortetracycline—was given at doses comparable to those approved by the U.S. Food and Drug Administration as growth promoters in farm animals. After 7 weeks, the group of mice on antibiotics had significantly more fat than a control group drinking plain water, the team reports online today in Nature. “This confirms what farmers have shown for 60 years, that low-dose antibiotics cause their animals to grow bigger,” Blaser says.

Read more at:  The Global Innovations

Now, Researchers at the University of Copenhagen, Denmark, and University College Cork, Ireland, found that antibiotic concentrations within limits set by US and European Union (EU) regulators are high enough to slow fermentation, the process that acidifies the sausages and helps destroy foodborne pathogens like Salmonella or E. coli.

“At low concentrations and at regulatory levels set by authorities, they could see that the lactic acid bacteria are more susceptible to the antibiotics than the pathogens are.

“Residual antibiotics in the meat can prevent or reduce fermentation by the lactic acid bacteria, but these concentrations do not effect survival or even multiplication of pathogens.”

Antibiotics used as growth promoters or to treat disease in livestock can eventually end up in meat, and regulators in the US and EU have set limits on the concentrations of antibiotics in meat for consumption by humans.

Researchers say that fermented sausages occasionally cause serious bacterial infections, but it’s never been understood why that might be….

Read more at: sciencecodex

Related articles

 

 

 

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Patient Access to Medical Devices — A Comparison of U.S. and European Review Processes

Reporter: Aviva Lev-Ari, PhD, RN

 

Saptarshi Basu, M.P.A., and John C. Hassenplug, M.Sc.

N Engl J Med 2012; 367:485-488  August 9, 2012

The U.S. process for approving innovative, high-risk medical devices has been criticized for taking longer than the European approval process.1 This contention is often used to support the argument that the Food and Drug Administration (FDA) should lower its standards for approving medical devices, since a slow approval process is delaying Americans’ access to innovative and lifesaving technology. But a review of the data, using appropriate end points, suggests instead that it takes the same amount of time or less for patients to gain access to innovative, high-risk medical devices in the United States as it does in the four largest European markets (Germany, France, Italy, and Britain)2 — largely because patient access is generally delayed until reimbursement decisions are made, which often takes substantially longer in Europe than in the United States.

To compare the United States and Europe fairly on this front, three criteria must be considered: the level of device innovation, equivalent start and end points, and patient access as defined by time to reimbursement. First, we focused on innovative, high-risk devices because in the United States such devices require the strongest evidence of clinical benefit and are the subject of most debates about the relative effectiveness of approval processes in different countries. Furthermore, previous studies have shown that lower-risk devices achieve market access in a similar amount of time in the United States and in Europe.

Second, an accurate comparison of time to market access requires measurement of the total time that elapses between application submission and market access. Previous studies have compared the chronologic dates of application submission and market access, but the date an application is submitted varies from country to country.

Third, patient access should be equated with the availability of reimbursement rather than with device approval, because broad patient access to a new device doesn’t occur until reimbursement by a national or third-party payer is available. Previous comparisons of the U.S. and European systems have used the approval date to measure process duration, but innovative, high-risk devices don’t reach a market where most patients can benefit from them immediately after gaining regulatory approval, though they may be accessible to patients who can afford to pay out of pocket. Rather, there is a second level of review through which public or private insurers decide whether and at what price they will pay for a device. Generally, public systems take longer than private insurers to make reimbursement decisions, and significantly more Europeans than Americans have public insurance. Two thirds of the U.S. population is covered by private health insurance, whereas only a fifth receives publicly funded reimbursement, primarily administered by the Centers for Medicare and Medicaid Services (CMS).

For both private and public systems in the United States, the pathway to patient access to a device starts with the submission of an application to the FDA. The FDA reviews innovative, high-risk devices for safety and effectiveness (clinical benefit) under the premarket approval (PMA) process, and information on the duration of reviews is publicly available. In fiscal year 2011, the FDA approved 40 applications for PMA. The average review time was 13.1 months, with 8.4 months attributed to FDA review time, and 4.7 months to the time the agency waits for the sponsor to address deficiencies in the application (“sponsor time”).3 CMS provides reimbursement for the majority of devices when they earn FDA approval. For a limited number of devices each year, however, CMS conducts a national coverage determination in response to external requests for validation or for devices that have limited or conflicting evidence of clinical benefit. This process averaged 8.6 months over the past 5 fiscal years.4 Although it is difficult to obtain data on how long private insurers take to make coverage decisions, anecdotal information from private insurers suggests that decisions are made within a few weeks to a few months after FDA approval, depending on the amount and quality of evidence of clinical benefit.

In Europe, by contrast, most of the 27 member countries of the European Union (EU) have publicly financed health care systems; such systems cover approximately four fifths of the populations of the four largest device markets. All EU countries require devices to first obtain a Conformité Européenne (CE) marking, which refers to a symbol shown on products that indicates market approval throughout the EU. The CE marking process is conducted by for-profit, third-party “notified bodies” that have been accredited by a member country to assess device safety and performance but do not evaluate effectiveness (which requires more clinical data). Although publicly available data are limited, anecdotal information from notified bodies suggests that the process takes 1 to 3 months, excluding sponsor time.

Most European patients do not have access to innovative, high-risk devices as soon as the devices receive a CE marking. Each country must first make a decision about reimbursement, a process that varies substantially among countries.5 Though a CE marking can be granted on the basis of fewer clinical data than are required for FDA approval, European standards for reimbursement are often similar to or higher than those that the FDA imposes for device approval. European countries may require additional data on the device’s safety and effectiveness, as well as on cost-effectiveness.

In France, a centralized body makes reimbursement decisions after assessing the safety and effectiveness of individual devices. Reimbursement decisions in Italy are devolved to the various regions, and Britain and Germany conduct broader assessments of device types or procedures, rather than of individual devices. Typically, innovative devices not covered under an existing diagnosis-related group (DRG) require review under the lengthier Health Technology Assessment process, which assesses safety, clinical benefit, and cost-effectiveness. Government-provided information on time to reimbursement varies by country. Estimated time frames are an average of 71.3 months in Germany, a range of 36.0 to 48.0 months in France, a range of 16.4 to 26.3 months in Italy, and an estimated 18 months in Britain.

Using this information, we determined that the time it takes to bring innovative, high-risk devices to patients in the United States is similar to or shorter than that in the top four European markets (seefigureComparison of Time to Market in Premarket Approval and Reimbursement Processes.). The public (CMS) process in the United States takes approximately as long as those in Italy and Britain, approximately half as long as that in France, and less than a third as long as that in Germany. The difference in time to market access is even greater when it comes to private insurers (covering the majority of the U.S. population), which often make reimbursement decisions within a few months after FDA approval.

To further illustrate this point, we compared the time to approval for five innovative, high-risk medical devices available in France, Italy, and the United States (see tableComparison of Time to Market Access for Five Innovative Devices in France, Italy, and the United States.). These case studies indicate that the average time to market access for these devices was 26.3 months in France, 30.8 months in Italy, and 15.3 months in the United States.

These numbers may not fully capture the reasons why a device reaches the market more quickly in one country than in another and do not reflect experiences with all innovative, high-risk devices. However, unless one uses equivalent standards in terms of the level of risk, the start and end points of the process, and the key end point of market access, accurate comparisons cannot be made.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on August 1, 2012, at NEJM.org.

SOURCE INFORMATION

From the Office of Planning, Office of the Commissioner, Food and Drug Administration, White Oak, MD.

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Reporter: Aviva Lev-Ari, PhD, RN

This post addresses related issues On the Career of the Life Sciences Scientist and compliments the following two posts on this Scientific Web Site:

August 1, 2012 — Introducing Career Streams into Academic Research

https://pharmaceuticalintelligence.com/2012/08/01/introducing-career-streams-into-academic-research/

June 27, 2012 — Picturing US-Trained PhDs’ Paths and Pharmaceutical Industry’s Crisis of Productivity: Partnerships between Industry and Academia

https://pharmaceuticalintelligence.com/2012/06/27/picturing-us-trained-phds-paths-pharmaceutical-industrys-crisis-of-productivity-partnerships-between-industry-and-academia/

BEYOND THE “MALE MODEL”: AN ALTERNATIVE FEMALE MODEL OF SCIENCE, TECHNOLOGY AND INNOVATION

THE TRIPLE HELIX ASSOCIATION NEWSLETTER, VOLUME 1 ISSUE 3 JULY 2012

Hélice www.triplehelixassociation.org  Triple Helix X, 2012, Bandung, Indonesia . . . www.th2012.org

by Professor Henry Etzkowitz, President of the Triple Helix Association,  Senior Researcher, H-STAR Institute, Stanford University, Visiting Professor, Birkbeck, London University and Edinburgh University Business School

henry.etzkowitz@stanford.edu

Professor Henry Etzkowitz paper is based on his Keynote Address to the FemTalent Conference, Barcelona, Spain 2011

I am often asked: why is a man studying women in science? The answer to that question is: my mother. She graduated with high honors in Geology from Hunter College, a public women’s college in New York City during the 1930’s depression. I had long thought that the reason why she didn’t pursue a career in geology was

because of the depression, that there were simply no jobs. However, on a research trip to the University of Texas at Austin, I visited the Engineering School which had a “wall of recognition” at the main entrance, including the names of many distinguished professors and practitioners, all of them men, who had graduated during the 1930’s depression and pursued careers in Geology. Perhaps the reason why a woman did not pursue a career in geological science at the time, might be found in the gender dynamics of science and technology. The broader question is how the best results may be attained from societal investment in human capital formation.

Firstly, we will consider the implications of findings from a study done in the 1990s, in the United States, sponsored by the National Science Foundation, of women’s experience in academic science (Etzkowitz, Kemelgor and Uzzi, 2000) including over 400 in-depth qualitative interviews conducted in a dozen leading research universities in five disciplines: biology, physics, chemistry and computer science:

1. One of the lessons from this study is that in Europe and other countries, there is a move to introduce the American system of higher education, including tenure procedures, which put a very strong emphasis on early achievement which, as we shall see, has deleterious consequences for women. Higher education policy makers in Europe and other parts of the world may want to look more closely at its effects before introducing this system, which is now taken as the gold standard in higher education. The introduction of the tenure system is driven by

international ranking procedures which drive movement from a system of relatively equal universities. Before abandoning values of equality, it should be seriously asked if introducing extreme inequalities will overall advance or inhibit quality academic research, teaching, and innovation.

2. Secondly, I discuss the Vanish Box model, derived from a four country study, sponsored by the European Union, DG Research, on Women and Technology Transfer (Ranga, et. al. 2008). During interviews with women in US academic science on Athena Unbound study, some of them would talk about colleagues who were no longer in the department, they were now in jobs elsewhere. I interviewed some of these women leaving academic science, and found that they were taking up careers in science-related professions such as science journalism, technology transfer, museology. etc. They were using their scientific training in translating science into use and spreading the results of science to a broader public. Rather than being “lost to science” as presumed by the “Leaky pipeline” thesis of science career loss; they were pursuing work-life balance in their new careers. This finding inspired the study sponsored by the European Union on Women and Technology Transfer.

3. Third, I outline a four phase model of women’s experience in science, technology, and innovation, “the Vanish Box”: after the magic trick of the “disappearance of re-appearance of a woman”. “The vanish box” model shows the dynamics of the historical experience of women in science, and questions the taken for granted “male model” of science that does not work for women or men who seek work-life balance.

4. Finally, we address the question of whether the Gender Revolution in science and technology is stalled or moving forward.

Gender Inequalities in Academic Careers

The historical relationship between status and gender provides a clue to understanding the underlying dynamics of women and men’s careers in science. Typically, there is strong participation of women in the early stages of development of a new discipline, but as the new area becomes prestigious and rewards increase, women disappear. As fields attain recognition and fruition, and the Nobel and other prizes are awarded, it is men who are there to receive them. There were a significant number of women working in “the fly room,” the drosophila genetics lab headed by Thomas Hunt Morgan at Colombia University, but as the field became prestigious, women virtually disappeared from classical genetics (Kohler, 1994).

Does this historical relationship between gender and science still hold today or has it changed? The most important finding from all the specific instances that we came across was that the most important thing holding back women’s advance in academic science was “inflexibility” of rules and procedures. It didn’t matter what the specific procedure was. For example, in the US it’s expected that that you should pursue your PhD at a different University than your undergraduate degree. This is the highest route to achievement. If a woman has a relationship, and the man moves will she leave the relationship to seek her competitive advantage?

On the other hand, if the man in the relationship moves, and the woman goes along, she may then have to move to a school that is not as good as the one which she otherwise might have gotten into with a broader range of selection. Thus, this informal rule of exogamy, mandating leaving the previous school or worksite at each point of progression, from undergraduate degree to PhD to entry level position, works against women’s advancement.

On the other hand, in Sweden the rule is the opposite. Instead of saying that you should move from one university to another, the rule is that you should stay at your own University; that if you are a highly successful junior scholar you will be kept within that University. A Swedish professor said, “why would I send my best

graduate student away? He is going to replace me when I retire.” So the rule in Sweden is endogamy that you stay within one university. Again, if a woman’s partner moves, and she moves with him, it will hurt her career, because she has left her university of origin. So which ever way the rule is, it is an inflexible rule, it has more negative consequences for women than for men. The gender policy implication is to increase flexibility in the system.

A female model of science, balancing work and family life, has been invented but it is a subsidiary and undervalued format that needs to be brought to the forefront and institutionalized. However, this would necessitate re-thinking aspects of the academic system, especially the US model, that unintentionally yet systematically works against women’s inclusion in the higher level of academic science. The US model of academic hierarchy, front loading in the academic career with a strong emphasis on youth and achievement

in the early years, is partly based on a mistaken idea that youth are more productive in science than people who are of an older age. That finding was documented in a study done by Merton and Zuckerman of “Aging and Age Structure” (1973). They found that “productivity was as high or even higher at the later stages of a scientific career”, and that makes sense. When you are more advanced in your career you have more access to resources, more

graduate students, more research associates, more people working with you. Co-authorship arises from having members of your research group being highly productive. Nevertheless, there is a strong belief that youth makes disproportionate scientific advances, and this has been the basis of a system in which there is a strong emphasis on early achievement during the first years of your career. There is a race to accumulate publications and research grants in order to be given a permanent position in a high status American University.

In Europe, the tradition has been once you are hired there is a probationary period and then you continue to be promoted or not. But in the United States there is a very sharp dividing line: an “up or out” system. The implications for women’s advancement in science, includes the contradiction between the “tenure clock”, typically of seven years, and the “biological clock”, the time when is possible to have children, and these coincide. Thus, women have to make the choice to postpone having children to after tenure, which then becomes their middle or late 30s. There were some women who didn’t want to postpone, and some of them rethought

their commitment to academic science and left for that reason. Occasionally, in some universities there has been some reform of these procedures to try to accommodate women by extending the clock. i.e. you can apply for a year extension to reduce your time in the workplace and/or take a break in order to have more time for one’s young children. Even this attempt to ameliorate the male model of science and make it more amenable to women’s

participation contains a contradiction: women are concerned that if they apply for this privilege that it will be held against them in the final review. The academic system requires a demonstration of full commitment to racing the clock, otherwise you will be viewed as insufficiently competitive. Moderating the conditions will be held against you, or at least that is the fear. The attempted reform has its dangers since many women feel that they may be given points off for taking advantage of the attempt to change the rules. The contradiction between the tenure clock and the biological clock encourages some women in academic science to seek an alternative career path.

An American professor talked about a leading female student who stayed in the same city and took a job at a local teaching college. But an exception was made for her because she was such an outstanding scholar that she was then brought back to the leading University in the same city where she had received her PhD and allowed to pursue a career at that university. The rule was counterproductive to the best use of talent, but this case was an

unusual exception. However, it is one that can be more regularly made if we are thinking of how to revise the system that works against women by following an implicit male model of science. Another negative factor is the “two out of three” time bind. In interviews in the US and Mexico, it was found that if you are trying to do three things, most women usually find it was too much, they could do advanced research in a highly productive way, and manage their family relationship, but that didn’t leave time for spending time in local politicking and talking with people, which is the way towards advancing within the academic system. So they could advance in their research career, but not in the career that would lead to becoming a chair person or administrator within academia. So this is the two out of three time bind.

Traditionally there has been a gendered division of labor where men worked with men and women with women, in gendered occupations. Some think that this occurred as a basis of naturally occurring gender divisions. But historically we can see that these gendered occupations change over time. I did my masters thesis on the male nurse, titled “the Precarious Identity of the Male Nurse” (Etzkowitz, 1971). The nursing profession in the

nineteenth century was entirely male, and began to change over to a female profession by the end of the nineteenth century, and by the middle of the twentieth century it was virtually entirely female. Thus, gendered professions can change over time and are subject to revision.

From “Leaky Pipeline” to the “Vanish Box”

The pipeline model has been based upon the movement from schooling into higher education and into careers; the premise that there should be an unimpeded flow. Over a period of twenty years, at maximum, women should be at the highest level of any occupation. Recruitment has taken place: young women now make up equal numbers in bachelor’s degrees, and the numbers are moving up in the PhDs. But they have not moved up at the same rate to the associate and full professor levels. The pipeline has not worked by filling it at one end, and expecting a changed result at the other. We need to make changes in the system to make the pipeline work. A gender neutral occupation would be one with flexibility in the role, and with balance between on-site and off-site work, and the possibility of equal participation of both genders in the occupation. What happens to women who, for one reason or another, don’t continue in an academic career in science? This was the question that we posed in: “Women in Science and Technology”(WIST) sponsored by the European Union. We identified that women who had left academic science, were reappearing in science related professions, using their scientific, networking and social skills in these new professions. In the UK, when opportunities opened up in the mid 1990s, female PhDs entered this career, following the States where women had risen to the top of their profession as heads of offices at major universities. From this study of women disappearing and reappearing from academia to science related professions, we developed a concept that we called the “vanish box” model (Etzkowitz and Ranga, 2011), that takes place in four stages:

1. The first is the disappearance of women: the disappearance that we found in the Athena Unbound study, the exclusionary practices, or the taken for granted male model of science which did not take account of women’s needs, of women’s life chances and lifestyles. They weren’t found at the highest levels of academic science to the extent that would be expected if the pipeline was working as it was supposed to, with women flowing in and being promoted up over a period of time. So disappearance.

2. The disappeared women are in the reserve army: at home or in part time positions unemployed or underemployed. The reserve army is called back when there is an emergency or a shortage. For example, during World War ll women PhD’s who had been unemployed or working as volunteers in their husband’s laboratory were called into full-time positions in the Manhattan Project and other Labs. After the War, some began to get academic positions and rose to the highest level after having been in the reserve army for many years.

3. The third phase of the model is the creation of new opportunities; either by emergency situations, or by the creation of new professions that require people with scientific training. An example of this was the Technology Transfer profession that we studied: a new profession that required people with scientific training and background and business training, and typically people with a scientific background would learn the business skills, take courses or even a master’s degrees in business. This provided opportunities, but there are still limitations: the new profession wasn’t as prestigious as the old one, and it had both advantages and disadvantages: working in a technology transfer office gives more of an opportunity for a work life balance, but the prestige of the profession isn’t that high and the opportunities for advancement are limited.

4. On the other hand, as the knowledge society advances, professions that translate knowledge into use become more prestigious and the profession also rises in status and prestige over time. That is what has been happening with technology transfer. The question that arises is, will it follow the same model of classical genetics, or will it lead to a new model of a gender neutral profession, with men and women working at the highest levels in a situation that allows for work-life balance? There is some evidence that this may be happening in small biotech firms. A recent study found that women recruited into these firms were taken seriously in their work, they were being promoted, and so the start-up biotechnology firm has offered evidence that there may be a changing relationship between gender and career advancement and new possibilities available in this area.

Beyond the “Male Model”: An Alternative Female Model

The American sociologist Cecilia Ridgeway has set forth the thesis of a stalled revolution, in the 1970’s large numbers of women entered professions in law and medicine but more recently advancement of women has halted. Pay differentials continue to exist. Women have not risen to positions in board of directors of firms to the same extent that might be expected. On the other hand, women now make up a majority of bachelor’s degrees recipients – over fifty percent in some places and as high as sixty percent in others. Forty years ago the percentage of women at MIT could be counted on the fingers of one hand. Today half of the undergraduate students at MIT are female. Once you get to the level of twenty percent social relations within organizations start to change; but they really transform at the fifty percent level. Typically in women’s entrepreneurship the service occupations make up the majority; but in Catalonia, there is a major change going on as the majority of the women in a program to support

entrepreneurship were in science and technology related occupations. The woman running this program said that the key issue is working with these entrepreneurs is how to grow their firms and still retain a work life balance. So the revolution is moving here. Academia is still resistant to change, but business has been moving faster, and Academia has to learn from industry. That is the next stage in making the gender revolution in science and technology.

To this end, the relationship between career structure and life cycle needs to be rethought (Etzkowitz and Stein, 1978). The current taken-for-granted career path is based on implicit male assumptions that do not take into account women’s greater responsibilities for family maintenance and societal reproduction that persist, even given good faith efforts on the part of men to play a greater role in child care (Kayyem, 2012). In the male model,

imposed on women as well, significant early achievement, typically involving a high time commitment, is the prerequisite for subsequent high-level positions. It is hypothesized that women’s difficulties in conforming to this model explains at least part of the variance in the paucity of women in high-level positions even as their participation rates increase.

An alternative female model, with a higher time commitment after child-rearing years, may be discerned. A Rockefeller University Professor, who started on her PhD at a later than usual age, and US Secretary of State Hilary Clinton, exemplify this alternative model that needs to be legitimized as an alternative path to high achievement. The current offering of a relaxed early career path in law firms is stigmatized as a “mommy track”

and reified into a permanent blockage to later high flying. When an alternative “female model” is available for women and men, gender democracy in science, technology and innovation, as well as in the larger society, will be a reality.

REFERENCES

Etzkowitz, H (1971), The Male Nurse: Sexual Separation of Labor in Society, Journal of Marriage and the Family.

Etzkowitz, H, and P. Stein. (1978) The Life Spiral: Human Needs and Adult Roles Journal of Economic and Family Issues. 1:4: 434-446

Etzkowitz, H, Kemelgor, C and Uzzi, B (2000), Athena Unbound: The Advancement of Women in Science and Technology Cambridge University Press.

Etzkowitz, H and Ranga, M (2011), Gender Dynamics in Science and Technology: From the “Leaky Pipeline” to the Vanish Box, Brussels Economic Review, 54:2/3.

Kayyem, J. (2012) The working moms debate International Herald Tribune June 27 Wednesday p.8.

Kohler, R. (1994) Lords of the Fly: Drosophila Genetics and the Experimental Life. Chicago: University of Chicago Press

Ranga, M et al (2008), Gender Patterns in Technology Transfer: Social innovation in the making?, Research Global, 4-5.

Ridgeway, C (2011), Framed by Gender: How Gender Inequality Persists in the Modern World, Oxford: Oxford University Press.

Zuckerman, H and Merton R (1972), Age, Ageing and Age Structure in Science. In Ageing and Society, Riley, M, Johnson, M and Foner, A, eds, Vol 3. New York: Russell Sage Foundation.

 

 

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