Philadelphia – ERT Headquarters

The Philadelphia Outreach Committee met earlier this year to evaluate a large list of nominated worthy organizations. After thorough review and discussion the committee selected The American Cancer Society (ACS) as a core charity, but also chose to support Alex’s Lemonade Stand, Philabundance, and Child Advocates.

The Philadelphia Committee decided to move forward with an ambitious schedule to include as many fundraising and volunteer opportunities as possible. The first event of the year was Alex’s Lemonade Stand. Many volunteer participants sold lemonade and baked goods at stands set up in the office building of ERT’s headquarters. The event raised $1,521.28 for pediatric cancer research.

In August, Philadelphia Outreach sponsored a supply drive for the ACS’s AstraZeneca Hope Lodge. ERT volunteers served dinner and socialized with the lodge’s guests. Although it may seem just like a dinner to some people, an event like this means a lot to the patients and caregivers who are undergoing treatment in the Philadelphia area. It creates normalcy in a time when nothing seems normal and as many of the guests stated, it gives them one less thing to worry about during this trying time. During dinner, ERT hosted games of Bingo with winners receiving one of five gift cards to Target. In addition to the evening’s events, approximately $500 in items from the organization’s wish list including cleaning products, paper products, linens, towels, and food were donated by ERT employees.

The committee kicked off the autumn sports season in September by hosting the first annual “Tailgate for a Cause”. Participants donated money and bought raffle tickets and in turn, enjoyed a “tailgate-themed” luncheon. [Definition: A tailgate party is a social event usually occurring in the parking lots of stadiums and arenas, before a professional sports game.] The event raised $1,182.00 for ACS.

October was another busy month for the committee. A group of employees teamed up to participate in the ACS “Making Strides for Breast Cancer”, raising $910 during a huge five-mile walking event in the Philadelphia area. ERT Philadelphia also participated in the ACS “Party with a Purpose Gala” as a Bronze Level Sponsor, contributing $5,000.  Also, as the holiday season commenced, different departments competed in a competition to bring in as much food as possible for the annual Philabundance Food drive. In total, employees and the committee donated over 500 lbs (approximately $1,000 worth) of food to Philadbundance, the region’s largest food bank!

The December Outreach event was a huge success when employees banded together and sponsored 81 under privileged and neglected children by donating toys, clothes, and gift cards to the Child Advocates program. Child Advocates provides legal assistance and social service advocacy for abused and neglected children in Philadelphia County. In addition to the employee donated gifts (estimated at $3,500), the Outreach Committee donated $1,200 worth of laptops for the program.

Just as important as monetary donations, is volunteer time. A group of ERT employees at the Philadelphia office generously donated their time by participating in the ACS “Road to Recovery” Program. Volunteers went through training sessions to provide transportation for cancer patients who do not have a ride or are unable to drive themselves, to and from treatment.

In total, including monetary donations as well as sponsored events, the Philadelphia Outreach Program was able to give over $17,397.36 to their selected charities, $8,338.28 of that coming directly from employee donations!

Bridgewater, New Jersey

After careful consideration, the Bridgewater committee selected the following organizations for sponsorship:
• American Foundation for Suicide Prevention (AFSP)
• American Heart Association
• Crohn’s and Colitis Foundation of America

On June 4-5, from dusk to dawn, ERT employees participated in the American Foundation for Suicide Prevention’s “Out of the Darkness Overnight“ event. Our brave participants walked an 18-mile stretch of New York City out of the darkness, shedding light on the issues of suicide and depression. Proceeds fund research, advocacy, survivor support, education, and awareness programs. The participants actively collected donations from friends and family and ERT was able to match their donations, raising a total of $5,836.

ERT participated in the American Heart Association – Heart Walk 2011 event on Saturday, October 1, 2011 in Bridgewater, NJ. Employees took a scenic 2K walk (OK, some ran) at Duke Island Park. The event consisted of a rally before the walk as well as many informational booths on the grounds to help raise Heart Health awareness. ERT sponsored each employee who participated in the walk and contributed over $5,000 in donations.  Donations were also made on behalf of ERT to the Crohn’s and Colitis Foundation of America in the amount of $5,525.

Germany

The German Outreach Team gave its support to the ANCKER.e.V. Training Center in Würzburg for sick children and their parents with a donation of €7350 ($10,000). The center works with children and parents to learn how to handle their illnesses and is involved with asthma, neurodermatitis, adiposity, anaphylasis, and ADS/ADHD.   The outreach team also wanted to make a personal contribution to the project and, with their own efforts, sold cakes to ERT employees, raising an extra €700 for the Training Center!

Peterborough, UK

The Peterborough Outreach Committee has gained momentum during 2011 and decided to give the assigned $10,000 to the Arrhythmia Alliance in support of a national advertising campaign, which encourages the formation and support of local patient groups. The launch of this campaign was on December 6 in the Peterborough office with a speaker from both the Arrhythmia Alliance and a Cardiac Nurse from the Peterborough City hospital. The Arrhythmia Alliance aims to improve awareness, treatment and diagnosis of cardiac arrhythmias as well as working to improve the quality of life for those who are suffering.

The UK office also raised £208.55 for Children in Need, an organization devoted to raising money exclusively destined for charities working with children in the United Kingdom. Additionally, several other brave ERT members in Peterborough decided to take on the mammoth 13.1-mile Great Eastern Run and raised over £500 in support of the British Heart Foundation.

Other ERT Corporate Charity Efforts

Heart disease kills more women than all cancers combined and as such, ERT decided to aid the American Heart Association’s efforts to raise money for their Go Red for Women Campaign by participating in National Wear Red Day on February 4, 2011 and raising $716 in employee donations.  Donations support medical research, awareness, education and community programs that will help women live longer heart-healthy lives.

Also, as we are sure most of you have not forgotten, in March of 2011, the north coast of Japan was hit by a horrible tsunami after an 8.9 magnitude earthquake occurred 80 miles offshore.  Tsunami waves caused massive destruction and massive loss of life in northern Japan.  During this tragedy, ERT provided the American Red Cross $5,000 USD in disaster relief aid.

One of our favorite charity events occurred on an early Saturday morning in April, when ERT contributed $3,500 to participate in the 4th annual Cystic Fibrosis Foundation Sports Challenge.  The Cystic Fibrosis Foundation Sports Challenge is a mini Olympic-style competition where teams from corporations, businesses and professional groups compete against each other in a series of fun, athletic events at the New Meadowlands Stadium (home to two NFL teams in northern New Jersey). View more photos.

Also, on September 24, 2011, ERT employees helped raise a substantial $21,767.11 dollars to help fight multiple sclerosis. ERT formed a Bike MS team for the fourth consecutive year because we know that riding 150 miles is nowhere near as difficult as confronting a lifetime with multiple sclerosis. In addition to supporting novel research projects around the globe, The National Multiple Sclerosis Society also provides much-needed education, programs, and services to everyone who is affected by MS – including the diagnosed, their friends and families, and the healthcare professionals who work with them.

Additionally, during the holiday season, ERT offered its customers a chance to nominate their favorite charity on ERT’s Facebook page for a $5 donation to be made in their name.  Popular charities included the Leukemia and Lymphoma Society, Wounded Warriors Project, St. Jude Children’s Research Hospital, The American Heart Association and others.  With 12 charities nominated, ERT donated a total of $60.

…AND THE GRAND TOTAL IS: $86,822.37!  The committee would like to express their extreme gratitude to the incredible staff and our colleagues at ERT. It is because of the time and generosity of the people, that the Outreach Program was such a huge success this year. We look forward to continuing this success in 2012!

During the development of oncologic agents, there are many cardiovascular toxicities to consider.  Oncologic agents may produce direct cardiac contractile depression, myocardial ischemia, alterations in blood pressure, myocarditis, cardiac tamponade, hemorrhagic myocarditis, endomyocardial fibrosis, and brad arrhythmias.  However, this article will focus on Torsade de Pointes, an uncommon and distinctive form of polymorphic ventricular tachycardia (VT) associated with QT prolongation.  As shown in the telemetry recording below, torsades can be generated into ventricular fibrillation and be fatal.

We use the ECG for many things in clinical research. We look for new rhythms such as atrial fibrillation, serious bradycardias and tachyarrhythmias, new conduction abnormalities such as heart block or fascicular blocks, changes in the ST segment and T wave and new myocardial infarction patterns, but probably the hottest topic over the last five or ten years has been looking for the prolongation of the QTc interval.

The problem during drug development, and the reason for all of the commotion about QT, is that torsades is very rare – even with drugs which are the worst offenders.  For Terfenadine (which started much of this concern) the incidence of torsades is only estimated to be about 1/50,000.  For antiarrhythmic agents like Quinidine, the incidence of torsades is higher (may be as high as 1-2%).  However, for the drugs that we are mainly concerned about, the risks of torsades are so low that traditional clinical trials simply aren’t powered to detect them and therefore, we need a surrogate marker in order to properly identify the drugs which may produce these harmful effects.  We use the QT prolongation as that surrogate since all of the drugs which produce torsades also prolong the QT.

The QT interval can be difficult to accurately assess as there are many factors that can affect the measurement, such as the heart rate.  In order to accurately compare QT values before and after dosing, you have to correct for the heart rate.  This is because the QT decreases as the heart rate goes up and increases as the heart rate slows.  The most common correction that has historically been used is the Bazett correction (QTcB = QT/ √RR).  Although the Bazett correction becomes increasingly inaccurate as the heart rate increases, it is unfortunately the QT correction which is most commonly available to sites.  The Fridericia Correction (QTcF = QT/3 √RR) is a better correction, particularly at higher heart rates.  The best QT correction is the QTcI, an “individual correction” that uses a unique algorithm for each specific patient.  However, to allow the calculation, this method takes approximately 40-50 ECGs at baseline and is thus limited in use.

Another difficulty is the normal variability of QTc over time.  In normal volunteers the QTc can vary up to 75 milliseconds over the course of a 24 hour period, and even to 90ms in subjects with underlying structural heart disease throughout the course of a single day!

As a biomarker, QT is not ideal.  This measurement, which can be difficult to assess, needs to be sensitive enough to detect quite small changes.  The ICH-E14 regulatory guidance sets out the rules for how to evaluate QT for drug development trials.  All new drugs with systemic bioavailability, regardless of therapeutic area and the preclinical profile, should have a thorough QTc/QT trial performed.  Approved products brought back for a new dose, new indication, new population or route of administration should also have a thorough QTc/QT trial performed.  Generally, the trial should be performed in healthy volunteers with placebo and positive control arms (to ensure assay sensitivity) and with both a therapeutic dose arm and a supratherapeutic dose arm, using multiples of the maximum expected dose, to simulate the worst case scenario.  The trial needs to define a 5ms effect with a one-sided 95% confidence interval that excludes a 10ms effect using time matched controls.

However, drugs which cannot be given to normal volunteers are the exception to these rules and it is not required that such drugs undergo a standard thorough QTc trial.  (The other exceptions are biologics, which generally do not directly affect the QT interval, and orphan drugs).

The current Oncology Division guidance is that it is necessary to characterize the ECG effects of a new oncologic agent to inform prescribers about potential cardiac toxicity and to suggest whether any additional monitoring would be recommended.  The degree of effect could weigh on risk/benefit decisions for approval, but usually, QTc effects of oncologic agents used for otherwise lethal illnesses are a labeling issue and do not hinder drug approval.

Listed below are oncologic agents which are known to prolong the QT interval.

Arsenic Trioxide, used in acute promyelocytic leukemia and sometimes in acute myelogenous leukemia, is the ‘granddaddy’ of all QT prolonging drugs.  Its efficacy was established before any ECG data was collected and early reports on arsenic did not identify any QT issues.  However, a formal Phase I trial showed a dramatic increase in QTc and a retrospective analysis was conducted to determine the degree of QT prolongation in patients treated with arsenic trioxide. The mean change from baseline was 47ms, with over a third of the subjects having a greater than 60ms increase.  To put that into perspective, remember the ICH-E14 guidance is looking for basically a 5-10ms effect, so arsenic trioxide, despite having a huge QT effect, is still approved for human use.

When assessing cardiac safety in oncology patients, it’s important to consider whether a compound can be given to normal volunteers or whether there might ever be additional indications for use in less critically ill patients.  When considering a non-cytotoxic agent, particularly if it has already been administered to healthy volunteers in earlier trials, one can assume that it will be necessary to perform a standard TQT Trial.  On the other hand, when dealing with a cytotoxic agent, in order to meet the requirements for assessing cardiac safety, one may instead do PK-PD modeling in dose escalation studies or perform an intense substudy in Phase III.  Of course, there are many confounding variables.  QT results from early Phase I trials in patients may be difficult to interpret due to co-morbidities, electrolyte shifts, all of the different concomitant medicines (including some of the antiemetics commonly used), inconsistencies in various Phase I protocols or a lack of validated results and designs.  All of these issues can burden planning and regulatory submissions.  In addition, performing dedicated cardiac safety studies in oncology patients can have an adverse impact on patient care and clinical centers, as many of these centers are not accustomed to doing intense cardiac safety assessments.

In assessing the QT interval, we generally recommend the use of 12-lead digital holters which collect 12-lead ECGs continuously for 24-48 hours.  This allows the ECGs to be extracted at particular time points which one has chosen based on the preliminary PK data.  However, if necessary, one can go back and extract additional data to observe if there was a QT effect at a time point which hadn’t been anticipated up front.  Additionally, we recommend the use of a central lab for standardized, manual readings.  We also usually recommend triplicate ECGs at each time point and as many as 6-9 at baseline.  This reduces intrasubject variability and the chance of finding a 60ms QTc “increase” that’s simply related to the subject’s normal daily QTc variability.

Generally, the ECGs should coincide with PK collection time points.  One will assess each patient for the change in QTcF and each dose cohort for the mean change in QTcF.  One can also assess QT/dose response and QT/concentration response on an ongoing basis as the dose is escalated.  For the best baseline, we generally recommend 2-3 triplicates (6-9 ECGs) spaced 5-10 minutes apart.  It is critical to have the best possible baseline data, as this data will be used for all subsequent comparisons for all post dosing time points.  On Cycle 1 – Day 1, triplicate ECGs matched to PK sample collection time points are recommended (if inpatient, typically 6-8 post-dose ECG time points over 24 hours or if outpatient, 4-6 post-dose ECGs in 6-8 hours).  During Cycle 1 (after Day 1) & subsequent cycles, depending on PK, additional ECGs (generally 1 –3 per time point) may be performed pre-dose and/or at Cmax on additional days.

The definition of a positive QTc signal will be a central tendency of greater than 10ms as well as PK-PD data showing greater than a 10ms increase in QTc at Cmax.  Positive signals may also include outlier analyses showing greater than 15% of subjects having a greater than 60ms change in QTc or greater than 5% of subjects having a new QTc greater than 500ms.

What are the consequences of a positive QT study?  The good news is, it doesn’t mean you have to cancel your development program!  In the face of a positive QT effect, one will need to perform more intense ECG monitoring in Phases II-III in order to be able to give good recommendations in the drug label.  This will allow clinicians using the drug to maintain adequate safety for their patients. On the other hand, a negative QTc study will generally mean that one only needs to perform routine cardiac follow-up during Phase III.

As previously mentioned, we recommend centralized measurement and interpretation of the ECGs because our experience is that site measurements and interpretations are very problematic and carry the risks of both false negative and false positive results.  Sites generally tend to depend on unreliable ECG computer generated measurements.  Also, sites may use different ECG machines, which may employ different algorithms for the correction of the QTc.  In addition, many oncology sites are not all that experienced upfront with performing electrocardiographic monitoring, and readers may be inexperienced and inadequately trained at precise QTc measurement.  To compound matters, many of these patients will have significant T wave and U wave abnormalities (very common in oncology patients) that make the QT measurement even more difficult to assess than in normal patients.

In summary, the assessment of cardiac toxicity and QT effects has become mandatory, but for agents which cannot be given to healthy volunteers, a robust Phase I or Phase III trial can be designed to adequately assess QT effects.  Careful planning and careful implementation are key to the successful collection and analysis of cardiac safety assessments of oncologic therapies.

A personal interview with Linda Deal:

Linda, how long have you been in this industry?

“I’ve been in the Pharma Industry since 1997, 14 years!  The majority, 12 years, has been on the Sponsor side.”

What do you enjoy most about it?

“This is easy.  Let me start by saying that for me, the best in life is people and the most important thing in life is being understood.  My career affords me the privilege to make understood some very deserving people, the patients suffering illness.  I work very hard to represent the patient experience in the complicated process of bringing safe and efficacious therapy to those in need.  That’s what gets me out of bed every morning!”

Can you tell us about your past experiences in health outcomes research?

“Absolutely. At Janssen Pharma (a division of Johnson & Johnson), as the Immunology Patient Reported Outcomes Lead, my primary responsibility was developing and integrating the PRO strategy within the end to end development process. Prior to J&J, I was head of the PRO Center in Global Health Outcomes Assessment at Wyeth Research, which is now Pfizer. I have also supported health economics and outcomes research for Wyeth, Research Triangle Institute, and Glaxo Wellcome. Also, throughout my career, I have designed a number of assessments now used in clinical trials as well as prepared over 20 regulatory briefing documents addressing PRO development and validation for supporting registration and labeling.”

In your opinion, what makes a great vendor?

“A great vendor is a partner that listens and can anticipate my needs providing experience and insights that assist in meeting my objectives.  And, of course, a great vendor delivers a quality product/service on time, managing my expectations if necessary.”

What will your role be at ERT?

“In general, I’m here to provide scientific input into the technology solutions that ERT offers to clients for collecting outcomes data that will eventually meet the clients intended purpose for the data.  I anticipate that there will be an educational component to the role as well.”

Where do you see the direction of health outcomes heading in the future?

“Now and in the future, Health Outcomes will play a central role in Sponsor organizations.  Since the release of regulatory guidance addressing the development and use of patient-reported outcomes, we’ve begun to see specific areas of expertise within health outcomes emerge in the larger and more innovative sponsor organizations.  What used to be a single generalist role is being parsed out into multiple specialized roles.

The patient and payers are being recognized and addressed as stakeholders in addition to physicians.  The specialization required to demonstrate value and measure subjective outcomes is becoming necessary to stay on the competitive edge in this industry.  These are exciting times for health outcomes scientists.”

How do you plan to play a role in shaping this space?

“I see my role in shaping this space as one of education and communication.  The health outcomes community has done a great job of organizing and spurring scientific advancements within our community.   I’d like us to reach out beyond our community to educate our clinical, biostatistics, regulatory and operations colleagues on the importance and relevance of our science.   Some still don’t appreciate health outcomes as a science.  I’d like to see that change.  How is it that I’ve been doing this for 13 years and am still asked, “What do you folks in health outcomes do?”

I’d also like to see us balance the scientific refinements of our methods with the practicality of the tasks at hand.  I’d like to play a role in prioritizing our scientific focus based upon the return on our efforts to the patients, physicians, caregivers and payers….sort of reminding the team to keep their eye on the ball.”

Do you participate in any charity or volunteer work?  If so, which is the most important to you?

“Yes, there is a wonderful program called “Communities in Schools”.  With cooperation from employers, employees can volunteer a couple of hours per week to young children in inner city schools who are having difficulty learning to read.  These are kids who simply need someone to sit down and read to them, pointing and sounding out words.  It’s very rewarding to see a child learn to read.

I once had a proposal from a 6 year old!  He even had a ring for me.  I still have that and wear it once in a while.  I told him that if I wasn’t married when he grew up and he still wanted to marry me, then I definitely would do it!”

What is your favorite vacation destination and why?

“There is no single destination that is a favorite.  I like to go any place that is culturally exotic.  I’m a true social scientist.  I enjoy observing and trying to experience the way of life of others.  No Club Med for me.”

What is your favorite motto?

“There is more than one.  The first is to “begin with the end in mind”.  Have an idea of where you’re going before you take the driver’s seat.

In the context of bringing novel and innovative therapies to market, I can be very persistent and impassioned about representing the patient perspective.  That can create a bit of irritation with my clinical and biostatistics colleagues.  I often find myself reminding them that “it’s the minor irritation that creates the pearl!”  When I insist, it’s always with the intention of delivering a better product/therapy.

In the case of evaluating the merits of an Outcomes Instrument’s ability to measure what it is purported to measure.  The motto I recognize is that, “It’s better to be generally correct, than to be precisely wrong [in what you’re measuring]”.  So, I give greater weight to accuracy than precision.”

Thank you Linda!  Have your own questions for Linda? Feel free to leave a comment below!

On August 23, 2011, the National Institutes of Health released a guidance entitled “Best Practices for Mixed Methods Research in Health Sciences”.  The mixed methods refer to the combination of qualitative and quantitative approaches to addressing the treatment and prevention of illness and important public health issues such as treatment adherence and disparities among patient populations.

While this guidance targets researchers applying for NIH funding, it also serves as a useful supplemental reference to the FDA’s 2010 guidance to industry on patient reported outcomes.  This NIH best practices guide provides useful definitions and parallels to the challenges faced by outcomes researchers in the Pharma and Biotech industry that are tasked with exploring and uncovering novel points of medical differentiation for the products they support.  For example, in describing the nature of qualitative research and its evidence, the NIH guidance states “… Qualitative data help researchers understand processes, especially those that emerge over time, provide detailed information about setting or context, and emphasize the voices of participants through quotes. Qualitative methods facilitate the collection of data when measures do not exist and provide a depth of understanding of concepts.”  When searching for the novel point of differentiation, it is often the case that existing measures are inadequate or lack the depth to capture salient concepts that are meaningful and understood only by the patients that experience an illness and during particular circumstances.

Another parallel of interest for the outcomes researcher is a section addressing teamwork, infrastructure, resources, and training.  All four are of critical importance to the Industry outcomes researcher challenged not only to develop the measurement strategy to support a point of medical differentiation but to oversee a plan for executing that strategy.  When developing a measurement strategy, it is important to acknowledge that “the questions driving the research initiative should determine the expertise required to address them.”  Multidisciplinary compound development teams require a breadth of disciplinary membership but also the depth of subject matter experts such as health outcomes scientists.  By understanding the NIH guidance and familiarizing with its references, health outcomes researches increase opportunities for securing a seat at the strategy table, exercising the depth of knowledge to facilitate an appreciation and regard for our science.   Infrastructure, resources and training are all critical components to successfully implementing an outcomes measurement strategy.  For an organization to reap the benefits of a measurement strategy, execution must be done well.  Understanding the existing infrastructure and processes is essential before refinements addressing a measurement strategy can be addressed.  This is especially important in an industry where delays in timelines can affect the future stream of revenues and resources are allocated among competing programs within a portfolio.

For access to the full NIH guidance, http://www.nih.gov/news/health/aug2011/od-23a.htm

Team ERT *Bike MS City to Shore Ride 2010-2011
Written by Michael Federico

In recapping my experiences of the 2010 Bike MS City to Shore Ride, I needed to keep one thing in mind, Murphy’s law.

—  Like leaving your bike shoes at home.

So, we adapt, we work as a team, and we find a solution.  A fellow teammate will bring a spare set of pedals and shoes. No problem, even my size. Thanks, Bill!  That morning, at 6am, we swap pedals and shoes and away we go.  In the back of my weary mind they don’t look quite right and sure enough, the left pedal falls off 12 miles in.  Turns out, we put the pedals on the wrong sides, which stripped out the crank!  So we ride with just the right leg for miles 12 through 18, hoping the rest stop was at 15…it wasn’t. This way is about the same as driving a Porsche with summer tires mounted backwards, in a snow storm – you can still go, but it takes more “skill” and a bit of lunacy.  But after all, the whole ride is about dealing with disabilities, so it was worth all of the inconveniences to help this great cause.

At mile 18, two bike shop trucks stop and after appropriate frowns and consternation, we have a solution with a new left crank.  I catch the team at the next rest stop.  There we see the famous woman riding in her 30th MS City to Shore, in a dress and heels on a steel, one speed bike.  Oh, by the way – SHE IS 85!

As we take off for the next leg, I made the mistake of standing up to hump over a hill and, GREAT, the right pedal works loose and strips out.  That’s ok; my left leg is fresh from its previous rest and I motor on for about 5 miles.  Another repair guy stops, more frowns and consternation, and he declares the bike dead. Bummer.  As I am waiting for the bus, the inspirational 85 year old woman pulls in and I get my picture taken with her!

As I ride the bus, we stop and pick up disabled riders and bikes along the way.  Nice folks, however, this cruising and stopping is slower than a one legged rider!

At the next rest stop, I jump off the bus and right to the Bustleton Bike shop (genius of a guy by the way).   Again, after the appropriate frowns and consternation, Mr. Bustleton decides that the right solution is the simplest one, Achim’s Razor.  We put a correct right pedal on the right side, but just a flat pedal, no binding, which is less stress on the threads.  Cool, Great, I don’t care if we duct tape, spot weld, pop rivet, or bubble gum it, I am finishing this ride!  Both pedals are finally solid.  Sprinting to the next rest stop, I finally catch the group!

[Wait.   Do you hear that?   I can hear my biggest sponsor..my mom,  all the way from South Carolina: "Gooo Michaaaael!"]

Guess who pulls into this rest stop as we are leaving?  The 85 year old woman!  This is amazing, she is pacing us, or we her!

The rest of the ride was thankfully uneventful – finally riding with the team again, and a great team it is (check out the special video we created below).  Many, many thanks to all of the repair guys I now know personally, the support team for the ride and the ERT team – captained by Dan Wick.  We had 14 riders and raised over $11,000!  It was a great trip and I met many great people.

If you laughed, chuckled or even smiled when reading this, please help make a difference in the fight against MS and volunteer, participate, or contribute to the team’s 2011 fundraising goal. http://bit.ly/ERT-MSRIDE.  We have again formed a team for Bike MS because we know that riding 150 miles is nowhere near as difficult as confronting a lifetime with multiple sclerosis.  In addition to supporting novel research projects around the globe, the National MS Society also provide much needed education, programs, and services to everyone who is affected by MS – including the diagnosed, their friends and families, and the healthcare professionals who work with them.

See you in September 2011!

The collection of patient self-reported data is becoming increasingly important and, in some cases, a regulatory requirement in the assessment of safety and efficacy, and to determine labeling claims.  Recent regulatory guidance and the introduction of the PRO and ePRO Consortia are helping to change the landscape with respect to patient self-reported data.  Featuring both the sponsor and partner perspectives, join us to hear from industry experts on best practices and how to choose the best methodology as part of your future Patient Reported Outcomes strategy.  This seminar will explore how sponsors and CROs can navigate the ePRO landscape from assessment planning right through to data submission.

Thus far, ERT has selected a few separate dates and locations throughout the US to bring the latest ePRO industry information to your backyard, at your convenience and entirely complimentary.  The all encompassing agenda features: Validating a gold standard instrument for ePRO, a review of the latest ePRO Regulatory Guidance and an introduction to the C-Path Institute’s ePRO and PRO Consortia, PRO Scale Selection, ePRO Modality Selection, and Data integration.

The full agenda, as well as the official dates and locations are listed below.

8:00 – Continental Breakfast

8:30 – Keynote Address:

The Value of ePRO – The Patient’s, and Only the Patient’s Perspective

AGENDA

· 9:15 - A review of the latest ePRO Regulatory Guidance and an introduction to the C-Path Institute’s ePRO and PRO Consortia - How the latest guidance impacts on the entire suite of ePRO methodologies and the pros and cons of employing each within your trial.

· 10:00 – Break

· 10:15 - PRO Scale Selection - How to best plan for success in your studies with respect to selection of the optimal diaries, scales and assessments for collecting your patient self-report data. Hear from an sponsor about their experience of the do’s and don’ts and review a case study demonstrating the approach they have taken.

· 11:00 - ePRO Modality Selection - One size does not fit all when it comes to ePRO. How impartial consulting and a technology-agnostic approach to ePRO ensures that sponsors match the right solution with specific patient population demographics and geographic locations.

· 11:45 - Data integration - A review of the technical and operational process required to ensure that your ePRO data is seamlessly integrated within your eCRF.

· 12:30 – Lunch

DATES AND LOCATIONS IN YOUR REGION

September 8, 2011 – Parsippany – Sheraton Parsippany (Click Here to Register)
September 20, 2011 – Philadelphia – Radisson Warwick (Click Here to Register)

Breakfast and lunch will be served at all locations.

We look forward to seeing you there!

At the start of the webinar, Jim surveyed the audience to gauge how the attendees view
centralizing spirometry data in relation to the cost of their clinical trial.  The audience was asked specifically”Does a centralized approach allow for a sponsor to collect higher quality data with a lower overall cost?” The responses were as follows:

64.30% of attendees agreed that a centralized approach results in higher quality at lower costs, while 18.60% of attendees believed a centralized approach yields higher quality but at higher costs, and 17.10% of attendees didn’t know.

As the webinar continued, Jim discussed why we are so concerned with Respiratory
diseases and the affects they have on society.  Statistics of compounds currently undergoing research in clinical trials for Asthma and COPD were also discussed.

Throughout the webinar, several pressing questions were answered, such as:

• What are the issues impacting the variability of spirometry values causing
  unacceptable data collection?
• Which measurements need to be controlled in order to best see a treatment effect?
• What is centralized spirometry?
• Why should you centralize spirometry data?

Jim proceeded to explain the differences between standardized spirometry, centralized spirometry, and the various combinations of the two, including: non standardized and non centralized, standardized with centralized review providing feedback on data quality, and standardized with centralized review providing feedback on data quality and optimization of data (Best Test Review).  The pros and cons of each approach, as well as the processes and levels of quality control performed were also clarified.

In closing, the goals of a centralized review process, the effects that optimized data can have on your clinical study, and the advantages of centralized Respiratory OverRead were reviewed.  The chart below represents a high level overview of the benefits centralization can have on your spirometry data.

As shown, the further you centralize and optimize your spirometry data throughout the study, the greater the percentage of acceptable data is collected, resulting in fewer patients, increased statistical power and reduced costs. 

Finally, Jim asked the audience the same poll question that began the webinar, only this
time the answers were slightly different.  After an hour of discussion, the proportion of viewers who thought that a centralized approach allows for a sponsor to collect higher quality data with a lower overall cost had significantly increased by 17.7% to 82%.

If you would like to view this webinar for the detailed overview of spirometry and the
process of centralization, please click the link below.  You may also request a copy of the presentation slides by emailing events@ert.com.

Click to View: Centralized Spirometry – Why do I need to Centralize?

As always, comments, questions and feedback are welcome below or via email.  Thank you for being a part of the ERT global community!

Chicago, Illinois is home to the Willis (Sears) Tower, Blues Brothers, hot dogs, and deep dish pizza, but most importantly this year’s 47^th DIA Annual Meeting.  The Annual Meeting has always been and will continue to be an important conference for ERT.  Exhibiting at this conference has allowed us to consistently provide clients easy access to our subject matter experts, as well as an opportunity for our staff and project managers to attend informational sessions and learn about the major trends and issues affecting the global pharmaceutical industry.  Many of ERT’s experts came to answer questions and say hello to customers, including Jeffrey Litwin M.D. (CEO), Keith Schneck (CFO), John Sory (Chief Development Officer and ePRO business leader),  Robert Brown (Senior Vice President of Strategic Partnerships), as well as several of our other Cardiac, Respiratory and ePRO product and service specialists. 

Traffic to the ERT booth was steady throughout the conference.  Our booth featured a new design with comfortable seating areas to hold meetings, as well as our popular (you could even say ‘famous’) coffee bar.  The coffee bar was once again a huge success, serving close to 3,500 cups of coffee. That’s over 50 pounds of coffee beans!  Our baristas, Warren and Madge, greatly appreciate all of the fine compliments you so graciously gave throughout the conference.  It appears the “DIA runs on ERT” after all, with comments such as “Your coffee has been my life saver all week” and “This is best espresso that I have ever had from anywhere” radiating from every corner. 

Visitors to the booth completed a brief survey, given on one of three iPads, regarding industry information.  With over 250 responses, the survey results are as follows:

Do you collect trial data in a centralized manner? (Using some form of technology at site where data is collected and stored centrally for analysis and reporting)

81% of respondents claim to collect clinical trial data in a centralized manner.  This supports the overall message of centralization and indicates that sponsors and supporting CROs strongly recognize the benefits of collecting and storing data centrally for analysis and reporting as the adoption rate continues to grow.

 What type of data do you collect centralized? (Select all that apply)

Participants were asked to select which types of data they centralize and were able to select more than one from the included options of imaging, cardiac safety, respiratory, ePRO, EDC and CTMS.  This graph depicts that industry colleagues are supporting the message of centralization and recognize its importance in terms of high quality results with better science, lower costs and most convenience.  With imaging, cardiac safety, ePRO, EDC and CTMS spanning all therapeutic areas, it is not surprising that centralized respiratory services came in at a lower percentage given the lower number of attendees who are directly related to this area of drug development.      

What benefits has your company realized as a result of collecting data in a consistent manner and storing centrally for analysis and reporting? (Select all that apply)

Participants were asked to select what benefits they have witnessed from central data collection including regulatory compliance, time to database lock, query reductions, data quality, data integrity, trial efficiency, internal decision-making, site performance and cost reduction.  Again, they were able to select more than one option.  While it is apparent many sponsors and CROs have experienced all of these advantages, data quality was the most recognized benefit, followed by time to database lock and regulatory compliance.      

What’s most important when selecting a vendor?

Among six other choices including cost, relationships, financial stability, response timeliness, previous experience/habit and other, over 60% of respondents cited quality as the number one reason to choose a vendor.

To show our appreciation for participating, those who completed the survey were automatically entered into a drawing to win a brand new Apple iPad2, compliments of ERT.  We were pleased to announce the winner, Rachell Chiao, from Roche.   

As well as paying homage to our clients with great coffee, an iPad giveaway, and having our own subject matter experts on hand, we were also there to reap the educational benefits the DIA has to offer.  You can read a brief recap of some of the interesting sessions our staff attended below.

Blurring the Boundaries Between Technologies: Examples of Next Generation Clinical Trial Technology Integration: This session discussed the importance of integrating various databases used in clinical trials by using single sign-on for multiple databases and trying to use data from one to populate another (i.e. data entered from IVRS directly loads into case report form for single data entry).  While this might be feasible for a sole provider of IVRS, case report forms and RTSM, it seems a long way off for vendor integration.  However, it was interesting to see that as company, ERT has been taking these same steps internally to increase efficiency, including single sign-on, system integration with My Study Portal and EXPERT, as well as integrating all product and data service lines into EXPERT v3. 

An Innovative Strategic Partnering Relationship: Can this Approach Revolutionize Drug Development?: This session discussed the increasing prevalence of preferred partnerships in clinical trials and how it has led to increased satisfaction between drug companies and CROs/vendors.  It was shown that there is a direct correlation to the size of the drug company and the size of the preferred CRO/vendor.  You can read more about ERT’s Strategic Alliance and Partnership Program here.    

Using Patient-reported Outcomes to Assess Comparative Safety and Tolerability: Methodological and Regulatory Issues:  This session started by stressing the importance of PROs being completed by patients.  Data was presented in various forms showing that patient symptoms are often underestimated by clinicians.  There has been recent guidance from the FDA corroborating this information and stating that whenever possible, PROs should be completed by the patient.  The session then moved into discussing the need to proactively collect safety PROs for patients throughout studies.  This would be a change to the current model in which information is only collected after an adverse event is reported.  By having subjects provide safety PROs throughout the trial, especially in a Comparative trial (active control arm of an approved drug in the same indication), drugs may be able to be brought to market due to a better safety profile even if the efficacy has increased from other drugs in the market.  This topic is especially relevant in cancer studies, as quality of life is a primary endpoint and treatments often have great side effects.  The concern from pharmaceutical companies is that if you collect more safety endpoints you will also need to report those end-points to the FDA and they will be included in drug labeling.  Therefore, a drug which did not include safety PRO throughout the drug development process may have fewer side effects on the label.

Electronic Patient Reported Outcomes (ePRO) How to Maximize Patient-reported Information for your Studies:  This session focused on how the choice of technology and close engagement with the patient is crucial to overall trial success. More and more, regulators are looking to ensure that Patient Reported Outcomes are collected directly from the patient, away from the clinic.  To do this successfully, sponsors and their technology partners must choose solutions that are right for the study, the site and, most importantly, the patient.  However, simply having a technology solution in place is not enough to ensure a successful trial.  It is important that the patient also feel engaged in order to increase compliance and retain them within the study.  Many different technologies were discussed both during the presentations and via the Q&A at the end of the session, which reinforced the choice now available to sponsors and their CRO partners in deciding on the right solution for the specific therapy area, study demographics and patient population. The underlying message appeared to be, “look after the patient and the data will look after itself”.

A Special Thank You:

We thank everyone who came out to see us last week and hope you enjoyed the coffee.  We can’t imagine after 3,500 cups that you didn’t!  ERT enjoyed meeting each of you and if you have any further questions regarding our products and services please leave a comment below or send an email to events@ert.com and a representative will get back to you right away.  See you next year in ERT’s home town – Philadelphia!

View Photos from the 2011 DIA

During the initial webinar, Dr. Kelly Posner first discussed the need for prospective suicidality monitoring and explained a method of prospective assessment which improves precision and reduces site burden by using the Columbia-Suicide Severity Rating Scale (C-SSRS).  Topics included early suicidality monitoring, the FDA Guidance and the rationale behind it, the problem with inaccurate and inconsistent definitions of suicidal acts, how the C-SSRS can accurately and reliably assess suicidality, and indications of its current use in clinical trials.  Dr. Greist then came on to introduce the self rated C-SSRS, or the eC-SSRS.  Dr. Greist discussed key concepts, the eC-SSRS in practice, appropriate subjects (younger populations, those with Alzheimer’s and cognitively impaired patients), and the many benefits the eC-SSRS has to offer.  Finally, Michael Federico presented a brief operational overview of the eC-SSRS which included information relating to study planning, startup and applications.    

Throughout the webinar, we held several small polls for our attendees to answer in order to assess how the industry views prospectively monitoring for suicidality using the C-SSRS and eC-SSRS.  The questions and responses are as follows:    

Do you agree prospectively monitoring for suicidality in your trial using the C-SSRS will reduce the number of positive reports?

73.30% of people strongly agree or agree that prospectively monitoring for suicidality in your trial using the C-SSRS will reduce the number of positive reports

Now consider the IVR or telephone based method of using the SSRS.  Is this an appropriate method of electronically administering the SSRS?

75% of people believe that the IVR or telephone based method is a very appropriate or appropriate way of electronically administering the SSRS

Will the eC-SSRS reduce the investigator burden as compared to performing all the C-SSRS via patient interview.

89% of people believe the eC-SSRS will reduce the investigator burden to some degree as compared to performing all the C-SSRS via patient interview.

The Q&A session that followed the initial webinar proved very valuable, providing our audience with an in-depth view of how to implement the eC-SSRS in their clinical trials.  Each speaker was given a significant amount of time to personally answer the most important questions and concerns from the audience.  These questions and answers have been used to create a formalized FAQ document that can now be found on our website.  Please visit http://www.ert.com/ec-ssrs-faq/ for more details. 

Also, if you would like to view either webinar please click on the links below or request a copy of the presentation by emailing events@ert.com. 

Click to View: Prospectively Monitoring for Suicidality in Non-Mental Health Indications

Click to View: Bonus Q&A Session

DIA, a nonprofit and professional association comprised of nearly 18,000 members, provides “a global forum for knowledge exchange that fosters innovation to raise the level of health and well being worldwide.”¹  The 2011 Annual Meeting presents expanded opportunities for people to contribute and learn, including forums, workshops, panels, symposia, and pre-conference tutorials. Highlighting hot topics in more than 25 interest areas from pre-clinical research through post marketing safety and surveillance, these sessions will positively impact innovation and ultimately patient care. 

Attracting the biggest names in our industry, the Annual Meeting offers insightful information on the major trends and issues affecting the industry worldwide, as well as a myriad of key networking opportunities.  With an anticipated 8,000 attendees from over 80 different countries, John Blakeley, Executive Vice President of ERT, commented that “The Annual Meeting is now the premier show within the industry.  It is great to come and meet our customers; we have forged a lot of very strong relationships because of this show.”  Attendees will include industry professionals, clinicians, patient representatives, and 20 plus regulatory agencies from all over the world.  For ERT, attendance at this show is a must!  Not solely for the purpose of meeting our customers, but also for our colleagues who are attending to reap the educational benefits regarding new developments in clinical research.   This is a thought-leadership conference; therefore, there is no better place for ERT (as the market leaders in our industry) to exhibit. 

This year, ERT will be showcasing our integrated solutions for Cardiac Safety, Respiratory and ePRO at booth #1335 in the exhibit hall.  Here you will find our specialty coffee, which won the ClinPage award for “best consumable” at the 2009 DIA.  Whether it’s your morning Espresso or Cappuccino to get the day off to a stimulating start, or an afternoon Iced Latte to cool you down, ERT will be serving up all of your favorite beverages.  Also, look out for your chance to win the Apple iPad2!     

Looking forward to seeing many of you there!

1. http://www.diahome.org/en/AboutDIA/Overview/DIAOverview
2. DIA 2011 Preliminary Program