Personalized Medicine and Mammograms What Does the Future Hold?

The mammogram debate had some added fuel to fire with respect to the value of screening for breast cancer.  This time it was an article from the November issue of the New England Journal of Medicine (NEJM). 

The article titled Effect of Three Decades of ScreeningMammography on Breast-Cancer Incidence by Archie Bleyer, M.D., and H. Gilbert Welch, M.D., M.P.H. highlighted that screening mammograms may indeed be resulting in an over-diagnosing of breast cancer.  This was discovered  through results of their study including Surveillance, Epidemiology, and End Results data to examine trends from 1976 through 2008 in the incidence of early-stage breast cancer (ductal carcinoma in situ (DCIS) and localized disease) and late-stage breast cancer (regional and distant disease) among women 40 years of age or older.   According to the article, 70,000 patients or 31% of those screened are inappropriately identified in having breast cancer of some significance and thus undergo needless intervention and personal distress.  I say “of some significance”, because per a prior presentation by Dr. Welch, these patients do indeed have evidence of cancer that meets the cellular definition but it may be very slow growing cancer, non-progressive, or even regressive; thus the patient will likely die of another cause not breast cancer.  Furthermore, the number of patients who present with late stage breast cancers has not decreased despite the push to get all women over the age of 40 to undergo screening mammography.  Finally, it was determined that the reduction in breast cancer-related mortality is not due to more vigorous screening but instead, the availability of more effective treatments.

Needless to say this article, caused quite a stir; enough for it to be covered by the national media.  Whereas the reactions ranged from further doubt over the value of mammogram to accusations of “junk science”, it was a comment from Dr. Len Lichtenfeld in an article by CBS News that struck a chord.  While Dr. Lichtenfeld, the American Cancer Society’s deputy chief medical officer, chimed in to impart the significant support for screening mammography from high-quality studies, he alluded that the next step is indeed more accurate prognostic indicators.  He concurred that over-diagnosis is in fact a problem due to imaging technology which “has brought us to the place where we can find a lot of cancer,"  and noted that  “science has to bring us to the point where we can define what treatment people really need." 

Enter personalized medicine.  As defined by the President’s Council on Advisors on Science and Technology and reiterated by the Personalized Medicine Coalition (PMC) “personalized medicine” denotes “the tailoring of medical treatment to the individual characteristics of each patient…to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment.”  In other words, treating patients according to their prognosis; which means withholding treatment in cases for which the natural history will yield a good prognosis and when treatment is necessary, providing that which will afford the best response possible.

Can we use technology to determine prognosis and thus avoid unnecessary treatment of breast cancers that are unlikely to progress?  Moreover, if treatment is necessary, can technology ensure that the treatment is individualized?  To shed some light on this, I have performed a cursory review of technology in the areas of prognostics and treatment targeting.  By no means is this an exhaustive analysis – just an example of what is available now specifically for breast cancer or may be in the near future.

Risk Prediction

Myriad Genetics offers a blood test for the BRCA1 and BRCA2 genes (these are tumor suppressor genes located on chromosomes 17 and 13 respectively).  When mutated the BRCA1 (BR for breast, CA for cancer) gene is one of the genes responsible for hereditary breast and ovarian cancer.  These are known as “tumor suppressor genes”.  That is, when non-mutated, the proteins produced by the BRCA1 and BRCA2 genes prevent cells from becoming malignant by assisting in the repair of mutations in other genes through a process known as double-strained DNA repair.  Thus, an inherited mutation in either of these genes increases the probability of malignant transformation and cancer.  According to Myriad Genetics’ website, approximately 7% of breast cancers are caused by inherited mutations of BRCA1 and BRCA2.  This test is targeted to women who have close relatives (1^st, 2^nd, 3^rd degree) who have had breast cancer.  Its goal is to determine, through a numerical score, lifelong risk of developing breast cancer in those with a strong family history.

The OncoVue was developed by InterGenetics and unlike, BRCA 1 and BRCA2, is designed for women without a strong family history.  Its goal is to identify women at risk of developing sporadic breast cancer rather than hereditary breast cancer. Through a sample of buccal (cheek) cells obtained through oral rinse collection, according to InterGenetics’ website, OncoVue assesses a number of common variations in many genes involved in growth factors, DNA repair, steroid hormone metabolism, DNA repair, free radical scavenger, and cell cycle control.  Results estimate a woman's individual risk by assigning her to a standard, moderate, or high risk groups relative to the average risk for women of their age. It also gives women a score at different stages in her life.

Prognostic Indicators

Agendia’s Symphony is a suite of genomic tests which includes prognostics, targeting treatment, and companion diagnostics for developmental genetic therapies.  One component MammaPrint, is designed to determine the intervention strategy for patients with early stage breast cancer (stage 1 or 2) identifying the risk for metastasis.  According to Agendia’s website, this test interrogates the critical molecular pathways involved in the breast cancer metastatic cascade and analyzes 70 critical genes that comprise a definitive gene expression signature.  Results stratify patients into two distinct groups — low risk or high risk of distant recurrence.  A “Low Risk” result means that a patient has a 10% chance that her cancer will recur within 10 years without any additional adjuvant treatment, either hormonal therapy or chemotherapy. A “High Risk” result means that a patient has a 29% chance that her cancer will recur within 10 years without any additional adjuvant treatment, either hormonal therapy or chemotherapy.  The test is performed on a tissue sample obtained during lumpectomy.

Probably the technology most relevant to the debate triggered by the NEJM article is the Oncotype DX Breast Cancer Assay for DCIS developed by Genomic Health.  DCIS is the earliest form of breast cancer (a.k.a. “stage zero) which forms and is contained in the milk ducts of the breast.  It is also the type of breast cancer diagnosis which may be unnecessarily treated.  According to Genomic Health’s website, this test is a multi-gene diagnostic assay designed provide an individualized estimate of the 10-year risk of local recurrence (DCIS or invasive carcinoma) to help guide treatment decision making in women with ductal carcinoma in situ treated by local excision, with or without tamoxifen.  It analyzes the activity of 21 genes and then calculates a recurrence score number between 0 and 100; the higher the score, the greater the risk of recurrence.   As with the MammaPrint, the test is performed on a tissue sample obtained during lumpectomy.

Based on the examples provided, the industry is indeed beginning to move away from the treat-all approach for breast cancers, particularly in very early-stage cancer.  Genetic screening tests may help to in fact determine who needs yearly mammograms and when they should initiate.  While prognostic indicators do not obviate the need for a lumpectomy in the case of DCIS, they may reduce unnecessary follow-on radiation and therapies such as tamoxifen.

The level of interest we’ve noted in the business, clinical and patient community with regards to risk prediction and prognostic indicators is tremendous.   Clearly the debate will continue but the how cancer is diagnosed and treated is changing.    From the clinical perspective it will become more acceptable to not treat certain forms cancer based on genetic profile and prognostic indicators.  The ability to better predict drug efficacy will also further reshape the market and narrow the focus of many leading oncology drugs.  The genetic knowledge will also offer new opportunities for new treatments based on the human genome.  The payer community will also have to further adapt to treatment paradigm with more complex and informed treatment pathways.  The age of personalized medicine is upon us.  Personalized treatment and mammograms is just one example that will be reshaping the life sciences industry over the coming decades. 

Melissa Hammond is Managing Director at Snowfish, a strategic consulting firm specializing in providing unique insight to the life sciences industry.

 

Comment on Pfizer’s Report: Preventive Care and Healthy Aging

While there has been growing acknowledgement of the fact that our world is getting older, within the life sciences industry, geriatrics has often remained the proverbial elephant in the room.  That is why it has been encouraging to witness the focus of industry in the areas specific to the older population such as dementia.  In addition, we have observed certain companies taking an interest not only in specific conditions but in overall aging and even setting up business units that concentrate in conditions of aging.  This is evidenced by a recent report released by Pfizer titled "Preventive Care and Healthy Ageing" which was commissioned through the Economist Business Intelligence Unit. 

This report highlighted the significance of healthy aging and the value of preventative care with respect to reducing the cost of care and profiled eight countries: Brazil, China, India, Japan, Russia, South Africa, the U.K. and the U.S.   It not only summarizes the significant challenges that must be overcome to implement this approach, but also underscored the benefits that governments (and citizens) can reap by implementing certain changes. What resonated most was the following:

·       This is essentially an emerging market within a number of emerging markets.  The quickest growth in the older population is indeed taking place in Brazil.   

 

·       Breakthroughs in the treatment of chronic diseases such as heart disease have lengthened the average lifespan which opens up the risk for acquiring other diseases not common in younger individuals such as pneumonia and dementia.  People are also living longer with diseases requiring careful control such as diabetes.

 

·        It is not only the developed world that is experiencing demographic shift, but also developing countries.  While they the impact is beginning to be noticed, there is little focus on it.

 

·        Immunization in older individuals is a relatively inexpensive way to reduce morbidity, particularly with respect to such diseases as pneumonia, influenza, tuberculosis, and shingles.  However, unlike children, there are no formal immunization schedules, therefore the vaccination rates are significantly below the goal.  This is evident even in developed countries.

 

·         Technological innovation is key to promoting preventative care for older individuals.  It does not need to be very sophisticated; mobile devices can be quite useful.

In general, this report reinforced the notion that globally, we tend to take a very reactive approach to healthcare delivery which is counterintuitive to the care of older individuals.  While developed countries may provide the state-of-the art when it comes to acute conditions (e.g., gallbladder, bone fracture), we fall short on preventive care or healthy aging. As Richard Gilfillan, director of the US Center for Medicare and Medicaid Innovation at the Centers for Medicare & Medicaid Services was quoted, “we didn’t structure a system for someone who is going to live for 30 years with diabetes”.

There are multiple opportunities that may be gleaned from this report that the life science industry can certainly take advantage of through innovation and creativity. For example, there is significant opportunity for vaccine manufacturers to emphasize to health care practitioners, the importance of vaccination for older individuals and even partner with public health organizations to develop schedules similar to that for children.  Additionally, recognizing that patients may indeed require continuation of therapy for chronic conditions for many years after the initial diagnosis, the industry can ensure that these treatments are as effective and safe for a patient at 70 as it was at 50 and leverage this as a competitive advantage.

Please look out for the upcoming Snowfish white paper which will provide innovative thought for how the industry can leverage the significant opportunity afforded by this important demographic shift.

Driving Quality in Hospitals: Is it Process or Outcome?

As a consumer and life science industry professional I have always had an interest in understanding the differences between process and outcomes in a hospital setting and how they impact quality of care.  Are hospitals indeed developing adequate processes that can significantly improve outcomes? 

Multiple factors such as mandatory reporting (e.g., core measure reporting), payer reimbursement and incentives, value-based purchasing, and increasing transparency (hospitalcompare.com, LeapFrog) have proven to be a strong impetus for the improvement of the healthcare delivery process with a particular emphasis on quality.  One of the central tenets driving multiple initiatives is that if you develop and then implement a comprehensive or improved process that will yield better outcomes.  

Snowfish has recently analyzed this issue by reviewing conversations that we had with 100 hospital-based healthcare professionals to better understand the nuances between the two concepts of process and outcome.  Our discussions with Chief Executive Officers (CEOs), Chief Operating Officers (COOs), and Chief Nursing Officers (CNOs) yielded some fascinating insights.

Before I discuss some of our findings, I will offer a little bit of background on process improvement.  I recall my class with W. Edwards Deming at NYU Business School.  Deming studied process at length in the manufacturing environment in the late 40s and 50s in Japan and was integral to the post WWII emergence of Japan as manufacturing powerhouse.  He noted that by identifying failures in process and literally stopping the manufacturing line until the process was fixed you, could significantly  reduce overall defects and therefore create a more consistent and reliable products.  He noted that the key is to practice continual improvement and think of manufacturing as a system, not as bits and pieces.  He further posited that when people and organizations focus primarily on quality the quality tends to increase and costs fall over time.  He also noted that when people and organizations focus primarily on costs, costs tend to rise and quality declines over time.   GE borrowed many of Deming’s concepts when they developed the six sigma concept which is in essence the idea that 99.99966% of the products manufactured are statistically expected to be free of defects (3.4 defects per million).

So has improved process yielded better outcomes in the clinical setting?  I would like to first start to answer the question with what defines process in the clinical setting.  

Process in hospitals starts with staff training.   Through dozens of conversations and additional outside research we found that hospital professionals will define training differently.   Training programs usually are a hodgepodge of different programs and formats pulled from various sources.  The preference at most hospitals is on free resources.  Approximately 66% of training respondents expect to pay between $0 and $100 per person/year for best practices training. The training formats cited most often include lunch and learns, in-services and web-based programs but also include conferences, checklists, documentation training, newsletters and a host of other random elements.  So training itself is not really standardized from one institution to another or even within the same institution and spending less than $100 per person a year really does not provide for robust training opportunities.

Another challenge is how is the effectiveness of training measured?  Unfortunately, there is not a consistent way to assess that the information was effectively learned and will likely affect behavior. Currently defining success in training can vary significantly from simple attendance (and not falling asleep during the class) to documentation and compliance with best practices (usually core measures) all the way up to demonstrating knowledge by using simulation technology. So the simple answer is that training is not even measured equally and effectively at most hospitals. 
An even larger question is whether all the critical elements that mark a successful process that drives superior outcomes (events, readmissions) are identified and being incorporated into the training.  To be fair, the hospital environment is far more complex than a manufacturing environment.   However, based on our discussions the hospital industry is still in its infancy in developing processes that will significantly improve outcomes.  For example, only one-third of hospitals are even measuring outcomes to evaluate the effectiveness of their training programs.  Clearly, a lot of work needs to be done.

So in response to the basic question I started with: are hospitals developing adequate processes to improve outcomes?  I would have to say it is a work in progress.  Clearly, things are improving but we are clearly in the early morning hours of a long day.    Just today, I heard Medicare is going to start reimbursing hospitals based on patient satisfaction surveys.  A high patient satisfaction rating will merit higher reimbursement from Medicare.  Lower satisfaction scores will reduce reimbursement.  Outcomes matter. 

 

KOL Mapping and Profiling an Evolving Paradigm

A decade ago, key opinion leader (KOL) identification and mapping was a bleeding edge concept. At the time, life science companies were using word of mouth and sales force recommendations as a primary means for identifying the thought leaders in a given disease state area. Using an analytical approach for KOL identification was a foreign concept to many. I recall spending hours with clients trying to convince them about the need to try a new approach that could yield superior results.

Fast forward ten years. KOL identification and mapping of influential physicians are now ubiquitous elements in marketing and medical affairs strategies. The demand for greater accuracy and granularity has led to increasingly sophisticated KOL identification processes involving the integration of disparate databases, value adding the data, independently weighing and scoring of all the data and developing sophisticated profiling.

KOL identification and mapping is designed to empower pharmaceutical and medical device companies. This is accomplished through targeting the ideal physicians with whom alignment will ensure a product’s success. However, we need to challenge ourselves and our life science colleagues to look beyond this group and intent and recognize where else we can apply this state-of-the-art approach to drive the business forward.

Firstly, there is no reason why a KOL identification and mapping needs to be limited to drugs and devices. There are other types of products and services such as diagnostic tests and training initiatives that are used by select segments of our industry. Analogous to drugs and devices, often their acceptance is driven by data and supported by highly respected individuals to whom the decision makers look to for guidance.

Secondly, why only target physicians? Our prior research involving over 500 Nurse Practitioners (NPs) and Physician Assistants (PAs) has identified this group as a vital component for healthcare delivery. In certain cases they represent somewhere between 5% to almost 20% of the market depending on a product class. In total, well over 100,000 NPs and PAs are delivering health services in the largest market. Additionally, these professionals are influenced by their peers. We also note a significant presence of the NP/PA role in Europe. Please click here to order our white paper on the NP/PA market.

Thirdly, why limit such analyses to only clinicians? Recent research has indicated Chief Nursing Officers (CNOs) and Chief Executive Officers (CEOs) are critical for the adoption of new training tools at hospitals. These individuals can be identified and profiled based on predefined criteria. Using advanced means, we are able to identify the top one to two percent that are the most likely to be purchasers of a solution.

Lastly, new targets do not have to be limited to individuals. The same approach for identifying and profiling individuals is highly applicable for profiling institutions and organizations. Our work with industry leaders has repeatedly demonstrated a strong desire to identify and reach out to associations, research institutions, and patient advocacy groups that form a product’s ecosystem. Similar to an individual, a detailed and complex profile can be built with a company’s unique requirements in mind. Once such service derivative based on KOL identification and mapping that target organization is a process we term, identifying strategic development partners. Strategic development partner identification enables companies to grow a product pipeline through identification of key potential partnerships based on multiple search criteria. For example, the process enables companies to identify thousands of institutions conducting early stage clinical work in given disease state area and then identify the top 1% of opportunities based on a company’s unique requirement. This saves thousands of hours and years of wasted effort. Everyone is looking to identify the next generation products, why not use a new process to assist you with that effort? To order the white paper click here.

We have personally witnessed the rapid adoption of KOL identification and mapping as an integral component for building a product’s awareness with physician audiences. We envision the next evolution as an expansion of the offering into new business areas such as diagnostic tests and training. We feel that KOL identification and profiling need not be limited to only physicians; NPs and PAs and even CNOs and hospital CEOs can be critical to a products success. Finally, associations, advocacy groups, research institutions, and corporate partners are all critical elements of a products ecosystem. Using the most advance techniques can help companies identify new opportunities that are critical to a company’s success. The KOL mapping and profiling definition has expanded beyond being simply focused on physicians.

Snowfish has seen this evolution and developed solutions to empower our clients to take advantage of this new opportunity. For more information please contact info@snowfish.net.

 

Your Critical KOL Identification and Mapping Questions: Answered

Over the past decade we have worked with leading pharmaceutical and medical device companies around the world to identify and map the key opinion leaders (KOL) that best fit their particular needs and objectives.  Over time we have heard a variety of questions ranging from why they should perform KOL Identification and Mapping to how best to do it.  We thought we might provide some answers and insights to these commonly asked questions.   Our sincere hope is that this provides you a solid framework to discuss KOL Identification and Mapping with your colleagues. 

1.      Why Undertake KOL Identification and Mapping?   Snowfish recently conducted a large survey involving over 200 physicians.  When asked, “what factors are the most important if your treatment selection?” the most important factor was clinical trial data.  Given the unalterable nature of clinical data it is the hand you are dealt. The second most important factor, and one which a company has full control over, is KOLs.   Over the past decade we have shown companies how influence is really concentrated in the hands of 1 to 2 % of the healthcare practitioners while 50% of the market has zero influence.  Another noteworthy point is that our survey pointed out that KOL is not synonymous with peer; recommendation from peers (not KOLs) was designated as least important. 

2.      How Can I Use the Results From a KOL Identification and Mapping Project?  We have most often implemented KOL identification and mapping projects on behalf of the Medical Affairs and Marketing departments.  The results are used in a variety of activities; developing advocates, establishing medical science liaison (MSL) regions, identifying speakers and advisory board members, determining with whom to collaborate on medical communications programs, and understanding the interrelationships with healthcare practitioners within the market.  Effective profiling performed as part of the identification and mapping will facilitate successful use of the results.

3.      Are Rx Volumes,  ICD-9 or CPT Codes a Good Proxy for Identifying KOLs?  Our research is that prescription, diagnostic, or procedure volume is probably one of the worst proxies for identifying KOLs.  The general characteristics of a KOL is a very well rounded individual who is conducting research, publishing articles, speaking at major events, and being in a leadership role at major associations along with seeing patients,.   The multitude of demands on a KOL’s time attenuates their ability to evaluate and diagnose the bulk of patients. The only exception is in the case of orphan conditions and still, these measures should not be used in isolation.

4.      To Compare the Cost of a KOL Identification & Mapping Can I Simply Divide the Number of KOLs Profiled by the Cost of the Project?  Unfortunately it is not that easy.  Advanced KOL identification and mapping involves the integration of dozens of data sources, unique profiling, and a clear understanding the product’s objectives.   The number of sources used, the level of manual data review, and the number of KOLs identified and profiled and the clinical experience of the team are all major factors that go into the pricing of the project.   Quite simply, having been hired to fix faulty KOL mappings, the value of each KOL is driven by the robustness of the data and insights behind them. 

5.      How Long Does a KOL Identification Mapping Take?  Doing a proper KOL identification and mapping projects takes time and thought.  We strongly advise against using a cookie cutter approach.   Our experience has been that a well done project usually takes approximately 10 to 12 weeks.  Given the importance of KOL identification and mapping, plan ahead for the project and make sure that the time it takes to do the project properly is included in your planning.

In the coming weeks we will identify other frequently asked questions we regularly hear from our clients at the outset.   KOL identification and mapping is a very important activity.  As we’ve documented, it probably is the most important activity that is fully within the scope of control of a company. KOLs drive awareness, understanding, and adoption of a product.  It is hard to envision anything as more important once a product has been developed. 

We welcome your questions, thoughts and opinions about this article.  If you have any questions please feel free to contact Audrie Bloom at Snowfish, (561)-694-1205 or at info@snowfish.net

Is the Physician Payment Sunshine Act Super for Physicians?

The power of Sunshine Superman and Green Lantern as Donovan penned in his ageless song from 1966 undoubtedly has nothing to do with section 6002 of the Affordable Care Act of 2010, aka, the “Physician Payment Sunshine Act”.  Nonetheless, this statute potentially wields some muscle of its own. This provision mandates that any company that markets a pharmaceutical, biological, medical device or medical equipment report all payments to physicians and teaching hospitals of over $10 or such equivalents to the Department of Health and Human Services who will then make this information publically available via a website. Realistically speaking, this includes anything from a pizza lunch to funding for a large clinical trial.
 
The mere mention of the Physician Payment Sunshine Act fuels extremely strong opinion, on both sides of the argument. On one hand, groups such as the Pew Health Group have actively been calling for such transparency.  They feel that such financial relationships between industry and health care professionals may likely result in conflict of interest directly impacting patient care decisions.  On the opposing side it has been asserted that such a measure poses significant risk to innovation as the valuable collaboration between industry and physicians may be tempered. 

We decided to evaluate the Physician Payment Sunshine Act from one perspective, that of prominent physicians.  We often engage physician experts in order to assist us with analysis of products and services for life-science companies.   Over the years we have literally worked with thousands of physicians and other health care providers.  Therefore, understanding their views of this mandate is of great interest to us.   

In an effort to get a diverse physician understanding of the multifaceted nature of the issue we spoke with fifty physicians from across the United States.   We asked them three basic questions around the Physician Payment Sunshine Act:

1)      Are you familiar with the Physician Payment Sunshine Act?

2)      Do you feel it is good for medicine?

3)      How do you think it will impact your interactions with life science companies moving forward?

Not surprisingly, the first question, are you familiar with the Physician Payment Sunshine Act generated almost universal awareness.  In fact, fifty out of fifty physicians were aware of the Act.

The second question around whether the Physician Payment Sunshine Act was good for medicine was far more nuanced.   Overall, 28% (14 out of 50) of physicians thought that the Physician Payment Sunshine Act was good for medicine.   We received multiple comments from physicians.  A typical comment from the Act’s supporters, “I have no problem with it; most patients are not going to look at it; transparency is important.”   Several physicians also commented on the potential for undue influence of money with comments such as, “if someone has received a lot of money from pharma that may influence their decisions” which is exactly what the Act is meant to address. 

There was also a relatively large undecided camp which represented 36% (18 out of 50) physicians.  In general, this group of individuals thought the spirit of the act was correct but the implementation of the act is flawed.   One physician commenting on the Act stated the pros and cons as follows, “the pro is that individuals receiving large payments make you wonder if they are using products because they are good for patients or the payments they are receiving.  The con is that every little gift gets reported which is too much.”  Another physician commented that, “I’m on the fence – does it help or hurt, it is far from clear.”

An equally large group as the undecided group, 36% (18 out of 50) physicians, thought the Physician Payment Sunshine Act was bad for medicine.  In general, physicians were quite concerned about the misperception that Physician Payment Sunshine Act may generate.  Our physician sample voiced multiple comments about the high cost of conducting clinical trials how this level of funding might affect public perceptions.  As one physician noted, “I understand the spirit of it, but the public will have a difficult time understanding it”.  Another remarked that “doctors work in different capacities; if I do a research study, the budget for it may be $750M the public may misperceive where and how that money came about and what I personally received.”  Several physicians commented on the Act’s potential to limit educational opportunities by casting “a stigma that limits education which is bad for medicine.” 

Last but not least, we learned that the Physician Payment Sunshine Act will likely have little bearing the interactions between leading physicians and the life sciences industry moving forward.   Of the physicians with whom we spoke, 76% (38 out of 50) thought it would not affect their interactions with life sciences companies.    A number of dissenters felt that the Act would impede the ability to have open dialogue with the industry, “it gets in the way of the conversation between the physicians and industry.”  

While 72% of the leading physicians with whom we spoke are either neutral or negative on the Physician Payment Sunshine Act, the positive news is that the vast majority will maintain their current level of interaction with industry.  This implies minimal impact of this mandate on research, educational opportunities and overall innovation.  Indeed physicians in general support transparency in medicine and other professions.  The devil is how to assess those interactions and ensure that the required reporting paint a true picture. 

Dave Fishman is President of Snowfish, a strategy consulting firm focused exclusively in the life sciences industry.

We welcome your comments!

www.snowfish.net

An Integrated MSL Strategy – Considerations for Your Company

Over the past decade, Snowfish has provided life science companies with a range of strategic services   designed to maximize the efficacy of commercial operations.  In this blog posting we discuss the interrelationship between the key opinion leader (KOL), medical science liaison (MSL) role, and KOL identification and mapping. 

Over the years we at Snowfish have noted the importance of KOLs in the ultimate success of a brand.  For example, we conducted research involving over 200 physicians, when asked specifically what influences their decision on which product to prescribe or use, after the clinical trial data, the second most important factor was the opinion of KOLs.  Given that clinical trial data cannot be altered, KOLs and how they are identified, engaged, and managed is indeed the most important modifiable factor in successful commercial operations.   

The day to day engagement of KOLs has traditionally been handled by the MSL.  Snowfish was interested in understanding how KOLs view the MSL role.  In order to gain greater insights we reached out to over 50 KOLs and gained their insights.  Not surprising, they highly value the MSL role as compared to the sales role.  In particular they regard the depth and knowledge a MSL is able to provide along with robustness of a free flowing discussion.  In multiple cases they specifically voiced their preference for engaging with MSLs as compared to a traditional sales call. 

Given the importance of KOLs and the importance they assign to the MSL role we wonder how many companies have fully explored the opportunity to maximize the efficacy of this important constituency.

Lending to the success of the KOL-MSL relationship is ensuring adequate time is allowed for meaningful relationship building.  This comes in the form of effective territory development for MSLs.  As part of our core offerings we conduct KOL identification and mapping for life sciences companies along with directly supporting MSL teams.  We have noted a lack of efficacy when MSL regions are simply an outgrowth of sales territories.  In the example below from a Snowfish client we were able to identify the top 250 KOLs for the product and then divide each territory based on four independent factors.  The first factor was the top 250 prescribers located within an MSL region.  The second factor is the grouping of physicians by common address and identifying the top 250 addresses.  The third factor is the grouping of physicians by a common business name.  Finally, we then place the top 250 KOLs into the predefined MSL territories based on the sales regions. 

What becomes instantly apparent is that the sales regions are not a good method for drawing MSL regions.  For example, Sue in the Mid Central region has only 1/6^th the number of KOLs in her region as compared to Mike in New England.  Given that most companies try to assign somewhere between 30 to 35 KOLs per MSL you can look at the various regions and see the misallocation of resources. 

Granted the importance of KOLs which we’ve documented over the years, plus the value KOLs assign to the MSL, an integrated and data driven strategy is critical for maximizing the commercial opportunity.   We welcome your comments and thoughts about this posting.  We have also developed white papers on MSL training and KOL identification & mapping and will be happy to make them available.

Geriatric Opportunities in Pharmaceutical Product Development: What’s New? What’s changed? What’s needed?

This article focuses on three critical considerations in the planning and development of drugs targeted at the geriatric population that present enormous opportunities for the forward thinking life sciences companies. We highlight two current products Pradaxa and Xarelto and discuss the geriatric impact on them as examples of challenges the life sciences industries confront.   In the last website posting, we looked at three of the recommendations that addressed the critical need for the industry and key stakeholders to change the way we all do business to prepare for the upcoming elderly population explosion.  The basis for both articles is a retrospective analysis of the 1990 Institute of Medicine paper “Drug Development for the Geriatric Population.” We plan to conclude the series with some specific recommendations for leveraging the geriatric opportunity.

Three recommendations from “Drug Development for the Geriatric Population” are analyzed below with an eye to the future.

1.    Consider cost-containment policies.  This in fact suggested a re-consideration of cost-containment policies related to medication coverage in the elderly.  The grounds for this recommendation were based on that in certain situations failure to use a certain medication may result in severe consequences for which the treatment may outweigh the cost of the actual medication. This involves a careful cost-benefit analysis to show that not using a certain medication will in fact raise the cost of treatment. 

At the time this document was written, Medicare did not cover outpatient medications. While the majority of seniors held additional Medi-Gap policies, these did not include prescription benefits. In 2006, enacted as part of the Medicare Modernization Act of 2003, older individuals were now eligible for formal Medicare prescription plans (Medicare Part D) either through Medicare Prescription Drug Plans (PDP) or Advantage plans. 

At the same time these plans offer the geriatric population greater access to medications overall, they are still somewhat restrictive.  Given the latest news regarding the elevated stroke risk in older women with atrial fibrillation (AF) regardless of anticoagulation status, we looked at the availability within these plans, of newer agents approved for stroke prevention in AF, specifically Pradaxa and Xarelto.  In clinical trials in which the median age was 71, Pradaxa demonstrated an advantage over warfarin while Xarelto was comparable.  Both agents obviate the frequent monitoring and dietary restrictions required for warfarin therapy.   We evaluated formularies for Medicare prescription drug benefits offered by two of the top health insurers in the U.S (one was a PDP and the other an Advantage plan) to determine coverage of these agents.  The Advantage program did not cover either drug.  Although the PDP offers both drugs, they are Tier 3 with an associated co-pay of $35-$45 and necessitate prior authorization.  In comparison, warfarin is Tier 2 with the co-pay ranging from $8 to $12 with no prior authorization required.

The issue of prior authorization for Medicare plans has been increasing.  Based on results of the Avalere Health Analysis in 2011, the percent of drugs requiring prior authorization has increased from 12.8% in 2008 to 16.7% in 2011. 

2.    Quality of life endpoints.  This would expand endpoints beyond efficacy and safety to evaluate those such as measures of cognition and function.  For example, if the drug results in delirium or incontinence.

Review of the literature, commentary, etc. has revealed that there is still a call to action for such endpoints.  To confirm this, using the website clinicaltrials.gov we performed a search of all interventional trials involving patients >66 years of age in which “cognition” was included as an outcome measure.  Out of 209 trials, only five did not evaluating therapies for diseases involving the brain such as Alzheimer’s and Parkinson’s disease.  Although there is significant interest in including such endpoints for drugs used in older individuals, the level of importance has not been recognized by industry.

Efforts are being made by regulators to encourage the inclusion of such geriatric-specific endpoints.  In the U.S. and in Europe, regulatory bodies have stated the goal of ensuring that drugs used primarily in the older population have been in clinical trials which adequately represent these patients.  The document titled Guidance for Industry:  E7 Studies in Support of Special Populations: Geriatrics states that “certain specific adverse events and age-related efficacy endpoints should be actively sought in the geriatric population, e.g., effects on cognitive function, balance and falls, urinary incontinence or retention, weight loss, and sarcopenia.” 

3.    Discontinue use of unsafe or unneeded drugs.   This involved a review of the drugs being used in older patients and how they are used.  Based upon this assessment, if a particular product is not demonstrating benefit in this patient population or places them at an increased risk for an adverse drug reaction, a suitable alternative should be identified.  

Not long after this recommendation was made, the Dr. Mark Beers in collaboration with other experts released the Beers Criteria for Potentially InappropriateMedication Use in Older Adults, informally known as Beer's Criteria.  The criteria is a reference for healthcare professionals as it outlines drugs for which the risks outweigh the benefits in those 65 years and older.  With a handful of revisions since its inception, the Beers Criteria remains the foremost guide to drugs which either pose high risks of adverse effects or seem to have limited effectiveness in the geriatric population.   Currently it categorizes drugs in the following ways: (1) potentially inappropriate for older people because they either pose high risks of adverse effects or appear to have limited effectiveness in older patients (2) potentially inappropriate for older people who have certain diseases or disorders because these drugs may exacerbate the specified health problems (3) used with caution in older adults.

In the meantime, other tools have been developed including the Screening Tool of OlderPersons’ (STOPP) criteria.  Furthermore various mechanisms to reduce the prescribing of potentially inappropriate drugs (PIMs) in the elderly have been put in place at the regional and local levels.  Regardless of available to tools and initiatives, considerable use of PIMs persists.  A study from a group at Weill Cornell Medical College identified 38% of U.S-based older adult patients receiving home care were prescribed at least one PIM.  A similar prevalence was found in Australia in which almonst 50% of a sample of community-dwelling older adults was found to use at least one PIM.   Lack of awareness among the general community of healthcare professionals may be one major reason for this relatively high rate of PIM use.  A survey  of eighty-nine physicians revealed that despite the fact that an estimated 25% of their practice consisted of patients > 65, many exhibited a poor knowledge of PIMs and were unaware of prescribing guidelines such as the Beers criteria.  

There is still much to be accomplished with respect to pharmaceutical management of older adults in order to address this great demographic shift.  Nonetheless,  this offers a wide open opportunity for industry to demonstrate innovation and product differentiation.  The next post will provide a framework for what the industry could be doing to leverage this potential by means of product development efforts.   In the meantime, I look forward to your thoughts on this analysis.

Extending Product Protection, What about Geriatric Exclusivity?

This is the first in a series of posts which emphasizes how life science product manufacturers should be cognizant of the growing elderly population and the opportunity that it affords.  This inaugural post of the series discusses the potential for obtaining geriatric exclusivity for certain marketed pharmaceutical products.   

Most companies are familiar with filing for pediatric indications.  Since 1997, the opportunity to obtain pediatric exclusivity has allowed companies to further differentiate their products as well as gain an additional 6 months of protection against generic competition.  Pediatric dosing makes excellent sense as drug metabolism in children differs from that of adults thus increasing the risk of adverse reactions and lack of efficacy.  Such differences are even observed across the span of the pediatric age range.  Without specific dosing in the label, clinicians are playing guessing games with their young patients.

When you take a careful look at the pediatric situation with respect to the value of specific dosing, it is easy to see how this parallels the geriatric field.  While many in the pediatric community warn that children should not be treated as little adults, it could be also cautioned that the elderly should not be considered as vigorous adults.  Most clinicians feel that it is absurd to treat an 8 year old in exactly the same manner as someone who is 35; why should it not be just as illogical for a 75 year old to be treated the same as a 35 year old?  By its nature, aging impacts the pharmacokinetics and pharmacodynamics of many drugs.  Reduced hepatic metabolism (as low as 30-50%) secondary to changes in hepatic blood flow, liver mass and hepatic endothelium, reduction in renal function and increased volume of distribution of lipid soluble drugs all increase the elimination half-life of a drug.  Altered sensitivity, common to several drug classes of drugs, results in accentuated effects in the elderly.  Put together, this gives rise to an increase in adverse events in this population. Accordingly, the medical community is making due by practicing by the adage of “start low, go slow” and in general, cutting the dose of many common medications in the elderly.  Still, as these doses were not clinically studied, it is not clear if as adverse events are attenuated the drug’s efficacy is being jeopardized.

Why haven’t we heard more about geriatric exclusivity?  Relative to the overall medication use in the U.S, the elderly are a sizable population.  Although the 65 and older age group comprises only 13% of the population, they account for approximately 34% of prescription medication use. [1,2]  Moreover a recent survey conducted by the CDC’s National Center for Health Statistics reported that almost 90% of individuals 60 and older had used at least one medication in the past month and 76% reported two or more.   And the geriatric market is only going to grow as the baby boomers age and the lifespan continues to extend.  By the year 2030, the number of Americans 65 years of age and older is expected to grow to 71 million with those 85 years of age and older representing the fastest growing segment of the population.

It would make logical sense that drugs used disproportionately by the elderly would already have geriatric-specific dosing in their labeling.  This is not the case.   Indeed, in a study performed by Steinmetz, et al, looking at the 50 oral drugs most commonly used by patients 65 and older in an in-patient setting, only 8 contained some form of altered dosing guidance in the label specific to geriatric patients.  None included age-specific dosing. 

In researching circumstances in which geriatric exclusivity was granted, our search yielded only one. In 2005, the FDA approved geriatric dosing for Savient Pharmaceuticals’ Oxandrin (an anabolic steroid indicated for weight gain) and granted the product 3-year marketing exclusivity.  This is quite notable given the exclusivity for adding pediatric dosing is limited to 6 months. 

So goes the question of why companies are not pursuing geriatric dosing as a way to attenuate competitive threat, both branded and generic. Unmistakably, this pursuit does not make for a “clean” trial as the elderly are more likely than their younger counterparts to have more comorbidities and thus be on other multiple medications.  This is most likely why so few patients of 75 and older are included in clinical trials in general, even for drugs that are very appropriate to them. 

The opportunity for industry is substantial.  In addition to the potential for an extra 3 years of exclusivity, providing specific dosing guidance for geriatric patients will likely result in providers using that particular drug over competitors or even generics.  They may feel confident that they can circumvent adverse events while maintaining the optimal level of efficacy.  What are your thoughts about geriatric exclusivity and why it is not being utilized by life science companies?

1.  Ferrini A, Ferrini R. 2000. Health in the Later Years. 3rd edition. Boston, MA, McGraw Hill.

2.  Centers for Disease Control and Prevention and The Merck Company Foundation. “The
      State of Health and Aging in America 2004”.

Melissa Hammond, MSN, GNP is Managing Director at Snowfish and a Geriatric specialist.

Nurse Practitioners and Physician Assistants: Taking a Closer Look

You might meet them when visiting a clinic or hospital ― clinicians who are not physicians, though perform examinations, order tests, make diagnoses, round, write prescriptions, and perform minor office-based procedures.  These are nurse practitioners (NPs) and physicians assistants (PAs).  

Recent phenomenon?  Absolutely not.  In the U.S., NPs and PAs have been practicing as far back as the 1960’s and 70’s when the professions were created in response to a shortage of healthcare providers.  This has since evolved into more than 150,000 NPs and 74,000 PAs in the U.S. according to the ACNP and AAPA respectively. 

Still, despite their history and rising numbers, there is opportunity to learn more regarding how these clinicians fit into the healthcare system.    This can impact decisions from business strategy to hiring.  I have compiled some facts to shed some light on this area.

The influence of NPs and PAs within the U.S.  healthcare system is likely to grow.  As a result of provisions included in the Healthcare Affordability Act, tens of millions more individuals will likely enter the healthcare system and as stated by an executive within U.S. Primary Care at Pfizer, primary healthcare providers are “already stretched way too thin.” Hence, according to the President-elect of the AAPA, the U.S. government is looking to NPs and PAs to take on a greater role to accommodate this growth, noting the healthcare reform language “talks about the physician, PA, and NP.”  This will also further facilitate the shift away from the individual provider model and toward the patient-centered “medical home”, in which a team approach is used to optimize patient outcomes.

NPs and PAs practice autonomously. A recent survey we conducted with over 500 NPs and PAs noted that while 81% reported having a physician on-site at all times, they diagnose independent of their collaborating physician 95% of the time. Furthermore, 66% of NPs and PAs reported making their own treatment decisions and 78% indicated that they make this decision independent of physician review 76 to 100% of the time. 

It is not uncommon to have situations in which there is no physician on-site.  “I am the lone provider and work with 8 psychotherapists a nurse,” says a psychiatric NP practicing in Kansas. She adds that her collaborating physician is located an hour and a half from her office. NP-owned/managed clinics already exist and are expected to expand if legislation being considered in 28 states is passed permitting NPs to practice without a physician collaborative practice agreement. 

NPs/PAs and physicians are not interchangeable. Though she emphasizes the similarity between a NP/PA and a physician “in the responsibility of diagnosis and treatment,” and that “the standard is the same”, a PA from Illinois makes it clear that she is not a physician.  “It is extremely important that I am aware of my limitations so that if I either have questions, doubts or suspicions about what I am seeing or hearing, I get in touch with my supervising MD.”  

The length of training is significantly shorter for NPs and PAs therefore they tend to concentrate on the less complicated cases.  This is not necessarily a limitation, as noted by the AAPA president-elect, for “it allows the physician to focus on the patient with the complex problem,” and therefore the NPs and PAs can “spend a little more time” with the less complex patients ultimately providing “a better experience” for them.  

NPs and PAs are not exclusive to the U.S.  The UK and Canada employ NPs and PAs with the model now being recognized in Japan.  The Netherlands began to train NPs in 1970’s as they faced a shortage of providers.  NPs are also found in Sweden, Australia, New Zealand, and South Africa.  Other nations including Taiwan have recently begun exploring the role. 

A top executive at U.S. Primary Care at Pfizer stresses that NPs and PAs are already valuable members of the primary care team. “We feel they are important customers and are seriously considering new ways of engaging them.”  Their team is using an interactive model to better understand how they can assist these clinicians obtain better outcomes for their patients and then customize the approach to based upon their practice interests. As put further, it is “not a one-size fits all approach.”  As stated by the Pfizer executive, “we’ve always engaged mid-level providers, but we need to ensure we’re having a dialogue with them, not just a one-way delivery of information.”  

Feel free to download our free white paper which offers unique insight on the role of NPs and PAs in primary care and beyond. 

Melissa Hammond, MSN, GNP is managing director of Snowfish, LLC.