Pharma Reform

I was recently surprised by my own indifferent response to a couple of recent pharmaceutical industry news reports that should have been shocking, if not mind boggling. One of them was:

 “Merck CEO defends hefty research spending” (Reuters).

Defend research spending?  Since when would investors be concerned about spending too much on R & D,  in any industry for that matter, but for pharmaceuticals? Are you kidding?

There are a couple of underlying issues that make this situation very disconcerting but understandable.  First, the article identifies “investors” as those who have expressed concerns about the amount Merck and other pharmaceutical companies are spending on R & D.   I’m pretty sure they are not talking about individual investors but rather institutional investors and investment analysts.

The problem is that these analysts and the firms they work for are mostly driven by short term financial results.  When long term corporate value-creation compromises short term financial gain opportunities, analyst and investment banking compensation (especially bonuses) can be negatively impacted.   For example, cutting corporate expenses to increase near-term earnings usually creates more positive stock movement and compensation opportunities than any long-term strategic investment will ever create.

Just look at the daily stock price ups and downs for pharmaceutical companies driven by a single piece of clinical data or a letter from the FDA.   For an investor market driven by a short term “make a quick buck” mentality, long term financial consequences become somebody else’s problem.

So why does Merck CEO Kenneth Frazier get so much attention for what is considered by some analysts as a questionably high level of R & D spending?  For most pharmaceutical company executives, their short term incentives are often similar to those of the analysts and investment bankers.   So, in this light, Mr. Frazier’s long-term perspective may be an outlier in not playing to the expectations of Wall Street.

Perhaps Mr. Frazier understands that innovation in prescription drugs is critical for the long term success of Merck.  Perhaps he understands that truly innovative new products are what pharmaceutical companies need to remain relevant and viable in the evolving new healthcare market.  Perhaps he realizes that a reliance on academia and small entrepreneurial ventures for innovative new products carries the risk of a limited supply. This reliance on outside sources of innovation could subject his company to the finite availability of viable drug candidates at any given time which drives up pre-approval (and sometimes before clinical proof-of-concept) prices (think Gilead $11 billion acquisition of Pharmasset) with no assurance the products will ever get approved.

Mr. Frazier gets noticed  and media attention because he’s in the minority of not playing to the investment analysts’ needs for short term financial gains that can drive stock prices up and provide investors with temporary gratification while handsomely rewarding analysts and their firms for being so smart.

It would be one thing for investors to insist on increasing the productivity and output of Merck and pharmaceutical industry R & D.  I have commented before  and the industry has proven that merely spending more doesn’t necessarily get you more innovative new products.   But, to suggest Merck is spending too much on R & D seems to me to be another attempt by analysts to drive for a near-term balance sheet excitement that can help them drive share price, temporarily.

I’m sure there is room for improvement in Merck’s R & D productivity but I believe that to outright suggest they are spending too much money on R & D is not in the best interest of Merck, its shareholders, or patients.   mike@pharmareform.com

Comparative effectiveness studies like the recently reported SATURN study comparing Crestor^® (rosuvastatin) with Lipitor^® (atorvastatin) sponsored by AstraZeneca may on the surface appear to be a big win for patients (and prescription drug providers) especially those awaiting generic versions of Lipitor (anticipated by the end of this year).  The reported preliminary topline results show a numerical advantage favoring Crestor but no statistically significant difference in the primary endpoint of the study (change from baseline in percent atheroma volume (PAV) in a ≥40 mm segment of the targeted coronary artery as assessed by intravascular ultrasound).

The apparent implication from these results is that there is no difference between Crestor and Lipitor and therefore, when available, generic atorvastatin will work just as well as the brand Crestor.  Extrapolating this “no difference” conclusion for a single endpoint to the totality of efficacy for atorvastatin could result in significant cost savings for patients and providers of prescription drug benefits.  You would think this is great news for patients but I believe the ramifications of this study go well beyond cholesterol lowering agents and the impact on future sales of Crestor.

Because of the investor interest, high media visibility, the enormous healthcare cost savings potential, and the mass market served by cholesterol lowering agents I believe there will be significant fallout from this study that is not necessarily beneficial to patients.

First, there are undoubtedly going to be patients who could benefit from Crestor rather than atorvastatin but who will not be given that option.  Smaller patient populations may never be studied well enough to determine if there really are patients who might benefit from one product or another in the face of large comparative trials showing no statistically significant difference.

Second, company executives have always been, but will now be even more, reluctant to sponsor comparative effectiveness studies for established products even when they feel they have an opportunity to demonstrate a difference (as I believe was the case for AstraZeneca).  The requirement for “statistically significant” clinically meaningful differences may be too high a hurdle (and represent too much risk) when complex trial designs are expected to prospectively identify a specific primary endpoint for a patient population with considerable variability.  We may, in an ideal world, feel we know enough about biology, disease pathophysiology, pharmacology, and the nuances of patient populations to be able to precisely design these definitive trials, but we probably don’t for most diseases.

Third, pharmaceutical companies may prematurely stop developing drugs they feel might not be able to demonstrate statistically significant differences to available therapeutic agents.  This would have been a catastrophe for antivirals HIV/AIDS treatments which we now know work best as cocktails of several products rather than one being “statistically  significantly “ better than another.  To further complicate this, regulatory approval studies are designed to establish efficacy and safety, not superiority.  I believe the need for demonstrating a statistically significant difference to meet market expectations and regulatory requirements for making a superiority claim (or to potentially gain approval) will make drug development near impossible where products already exist and efficacy is well established.

And if you are thinking about developing an as effective but “safer” product, good luck.  Regulatory requirements for claiming “safer” are even more challenging and from what I have seen, near impossible.

Lastly, this market expectation for demonstrating “superiority to available treatments” and regulatory requirements for making those claims, I believe will result in fewer therapeutic options for treating specific diseases (think antibiotic drug development over the past decade).  We are getting to a point where if a product is already available to treat a disease,  clinicians and payers want to know if your new product is better.  You would think this is not an unreasonable expectation, but it is an expectation that increases the cost, complexity, and uncertainty of drug development.

At the same time, pharmaceutical companies that demonstrate statistically significant differences for their branded products in comparative effectiveness trials will be able to command “super premium pricing” with an almost monopolistic “treatment of choice” position for the duration of their patent.  When a product demonstrates a clear benefit (statistically significant) over other treatments the bar is  raised for subsequent new products to demonstrate statistically significant superiority.  For products with trial supported superiority, regulators will have no choice but to allow superiority claims,  physicians will have little choice but to prescribe the product, and payers will have little choice but to provide reimbursement.  Unfortunately,  this also dampens drug development interest in therapeutic categories that already have well established “treatments of choice.”

And while we may have more effective and potentially safer products in the future,  if you think prescription drug prices are high now, just wait for these products that establish “treatment of choice” with clinically meaningful statistical differences.    mike@pharmareform.com

While it is hard to argue that you don’t need money to discover innovative new treatments for all the complex diseases that continue to cause illness, disability, and even threaten life.  At the same time, Big Pharma has shown that merely throwing money at discovery research won’t necessarily deliver the results you might expect.

As evidenced by many academic researchers and their teams, it is possible to discovered relevant disease targets and disease altering compounds with far fewer research dollars than Big Pharma has been spending over the past three decades.  Big Pharma R & D budgets, however,  are a misleading indicator of investment in innovation.   In other words, when Pharma holds out the total amount they are spending on R & D ($68 billion), you have to know that only about 30% of that is for discovery and preclinical research.  Still billions of dollars for a disappointing drug discovery return on investment.

Here is another way to look at pharmaceutical innovation productivity.  Let’s say the average Big Pharma has a $1 billion per year to spend on drug discovery and preclinical research.  How do you think that compares to what academic labs (or start up biotechs for that matter) have to spend on discovery research?  Maybe a couple million dollars they have secured in government grants?  Yet, dollar for dollar, who’s delivering the innovation? And why?  An increasing number and percentage of innovative new drugs are being discovered in government or government funded public laboratories.

While they may have less money to work with, academic labs have three essential ingredients that increase the probability for innovative drug discoveries;  expertise, time, and a passionate focus for a comprehensive understanding of the science behind their work (e.g., disease, pathophysiology, biochemistry, and molecular biology).

This is not to say that all Big Pharma researchers lack these essential ingredients.  But even if they do have them, these attributes are mitigated by the distractions of organizational expectations, bureaucracy,  and time pressures to deliver compounds rather than understanding the science.  Perhaps most importantly, expertise in Big Pharma is often rewarded with more work (projects, administrative duties, or increased management responsibilities) that removes (mitigates) the expertise, or at least the focus of the expertise, from the day to day work of discovery research.

Sure, more money can facilitates innovative drug discovery but without expertise, time, and a passionate focus on the science, don’t expect to fill your pipeline.    mike@pharmareform.com

In the previous post we discussed the CMS proposed ACO concept for developing healthcare provider systems that engage individual healthcare providers with “shared savings” incentives to improve the quality of care delivery and clinical outcomes as defined by 65 performance metrics.

Some pharmaceutical industry executives, healthcare providers, and even patients may view these performance metrics as a biased, bureaucratic process for defining medical practice and imposing the “cheapest, least expensive” treatment options.

Whether or not the ACO concept survives in its current form is not important, but rather, I believe it represents the next level of managing healthcare delivery that can not be ignored.   I believe the draft ACO concept also represents an important new context for how pharmaceutical companies need to be looking at developing, marketing, and selling their prescription drugs.  Here’s why…

For decades the pharmaceutical industry has boasted about cost savings, cost-effectiveness, and the pharmacoeconomic value of prescription drug treatment.  Professing that prescription drugs can reduce overall healthcare costs by avoiding the ancillary costs associated with chronic diseases, reducing office visits, keeping people out of the hospital, and most importantly, preventing and curing diseases.  And despite the industry’s best efforts, these claims and propositions have seemed to nebulous, lacking in credible data, and therefore mostly fell on deaf ears within traditional healthcare provider systems.

In an ACO-type healthcare delivery system, these value propositions have real meaning, especially as they relate to the defined performance metrics.  With electronic medical records, insurers, payors, and providers will now have more robust information systems to track and report performance of prescription drugs and validate the value propositions in their own healthcare system.  That means marketing and research must be aware of how their products will now be assessed against these performance metrics and design clinical trials that go well beyond establishing regulatory claims for efficacy and safety.

Getting your product identified as a “treatment of choice” in a performance metric would be the ideal and almost assure commercial success for a prescription drug in that healthcare system.  In fact, pharmaceutical companies who align their products and deliver data driven proof for improving healthcare delivery performance metrics as defined by ACOs will find healthcare provider systems more than willing to encourage the use of their products over other, less performance impacting therapeutic options.  Rather than trying to find ways to limit the use of seemingly expensive new products, this new perspective provides rationale for healthcare provider systems to proactively promote the use of prescription drugs that can help them meet or exceed their performance goals in a cost-effective way.

In the next post we’ll explore how healthcare statistics can provide an interesting platform for driving prescription drugs in this new performance metric, ACO-type healthcare provider market.   mike@pharmareform.com

The commentary and highlights of pharmaceutical industry challenges noted in Duff Wilson’s article “Patent Woes Threaten Drug Firms” in The New York Times (3/6/2011) and the Morgan Stanley report “An Avalanche of Risk? Downgrading to Cautious” come as no surprise if you have read the book Pharmaplasia™.  This disconcerting pharmaceutical industry situation has been decades in the making and unfortunately, will take decades to turn around.

Those looking for or postulating near-term quick fixes from strategic restructurings, mega-mergers, technology acquisitions, or breakthrough serendipitous discoveries to resolve the industry dysfunction will be sadly disappointed.  As described in Pharmaplasia™, the problems in the pharmaceutical industry are deep rooted and involve more than just a lack of  R & D productivity.

Sure there are going to be the occasional successful new product introductions that give us hope that the industry is recovering but even those introductions will have been the result of decades of development work and there will be too few to really make a significant impact on restoring healthy consistent revenue growth for the industry.  For the pharmaceutical industry there are no quick fixes and it could take decades for the impact of the multitude of strategic efforts today to really begin delivering the types of financial results expected from the magnitude of investment being made by the industry.

In addition to fixing R & D, the pharmaceutical industry business model must become more efficient (increase operational productivity and reduce waste), must be more responsive to healthcare market needs, and must replace traditional sales and marketing tactics with healthcare market embraced programs.  Success will depend on competent leadership that is more interested in satisfying evolving new healthcare provider needs and patient well-being than “driving revenues”, satisfying Wall Street, and building personal financial wealth.

In the end, a more prosperous future for the pharmaceutical industry will come from discovering and developing truly innovative new treatments that provide clinically meaningful benefits over currently available therapeutic alternatives.  This will take a major change in R&D philosophy with a much more comprehensive basic sciences approach to finding preventions, treatments, and cures for diseases rather than relying on historical “tweaking of chemistry” and “trial and error” approaches of matching compounds with postulated disease targets.   mike@pharmareform.com

As early as the mid- to late- 1980s the market started to become increasingly managed (think formularies) and the availability of many inexpensive generic antibiotics even then made it easy to set superiority expectations for new market entries.

About the same time, the widespread use of antibiotics rightfully started to raise concerns with the Infectious Disease community about the development of resistance.  Armed with microbiology data and clinical studies, formularies and treatment guidelines were developed to encourage appropriate antibiotic use.  Selectively targeted narrow spectrum treatments were preferred to the mindless routine use of broad spectrum agents.  To preserve their antimicrobial activity, the use of some uniquely effective agents was further restricted to prior approval by Infectious Disease specialists.

While these were responsible and commendable actions taken, they presented the pharmaceutical industry with a new set of expectations for developing antibiotics. The message was clear.  If you want your new antibiotic to be used and you want to be paid a premium price for it, you better have the data (comparative effectiveness) to support that it is better than what we already have (including generic alternatives) and be able to prove it is worth the money (comparative value) you want to charge.  And, even if it is that good and costs that much, we are going to make sure it is used selectively in only those patients who absolutely need it.

This wasn’t and still isn’t a very attractive investment opportunity for the industry given the ease of tweaking molecules and the lack of market resistance in other therapeutic categories. Even for companies that decided to have a go at antibiotic drug development, it hasn’t been a very easy road to market.  The few products that have gotten approved and done well were able to demonstrate or at least imply a clinical advantage over other drugs.

Now the industry and the FDA are faced with trying to figure out how to design trials that would allow for fair comparisons of different antibiotics.  Not satisfied with clinical “non-inferiority” the FDA and the industry seem deadlocked in trial design limbo.  More importantly for the industry, the market expectation is for superiority anyway. The company will need near impossible – to – obtain “substantial evidence” in their clinical data to obtain an FDA approved superiority claim needed to promote the antibiotic as superior.

Could other therapeutic categories become similarly unattractive for drug development?  When market expectations and regulatory hurdles become impractical and seemingly financially infeasible pharmaceutical companies will make one of two choices.  They will take on the task in hopes of beating the challenging circumstances so they can charge a super premium price when they bring that superior product to market.   Or, more likely, they will gravitate to therapeutic categories with lower market expectations and fewer regulatory hurdles.

Many pharmaceutical companies will fail making the first choice and many diseases will never have optimal treatments given the second choice.

mike@pharmareform.com

So what keeps representatives from having more engaging, more informative, and more credible discussions with physicians?  One of the most frequent reasons, or excuses, I hear about is the regulatory constraints placed on representatives.  Regulatory restrictions get in the way of being more effective as a sales representative when opportunities for product use exceed the label claims or where representatives could drive more sales by implying or even making comparative claims they can’t support with label claims or “substantial evidence.”

To ensure regulatory compliance, many companies, especially those with Department of Justice Corporate Integrity Agreements, now require representatives to stick to verbatim scripted presentations that mostly do not resonate well with physicians.  This “regurgitation of the company message” is an immediate turnoff for physicians, lacks credibility, and makes for awkward representative – physician interactions.

Now, keep in mind the premise of our discussion here. You are a professional representative and your mindset and focus is on making sure patients in your territory are getting the best treatment possible.  You are not just “driving sales” by doing and saying whatever it takes to get physicians to prescribe your product as much as possible.   Professional representatives don’t need to be reminded of fair balance or to stick to label claims and approved literature, they just do.  The challenge for them is whether or not they have the claims and sufficient regulatory compliant data and literature to meet the information needs of their customers.

Some sales representatives might suggest that they have all they need in terms of claims and published data and regulatory is just getting in the way.  If that is the case, then why would there be a regulatory compliance issue?  Why is regulatory review such a big deal?  Why would companies and representatives feel a need to promote off-label to make their sales? Why would companies feel compelled to script boring marketing messages to ensure sales representative compliance? More importantly, why is the market still clamoring for more comparative trials and better data to help them identify best treatment options for patients?

In this competitive market and knowing that products we now have were developed with a “get it to market “ mentality and indication – driven clinical trials to satisfy regulatory requirements for safety and efficacy, I’m going to suggest you do not have the claims or data you need.  How many of your products have two well controlled comparative efficacy trials to support claims of differentiation that you can use in sales presentations?  Can you claim superiority?  If not, how can you discuss why your product is better than another for a particular patient type? Can you do this and be compliant with regulatory requirements or are you expected to just cleverly implying a difference?

Here is the problem.   Even today, research gets the indications and it is up to marketing and sales to differentiate the product in the market.  When a physician or managed plan decision-maker asks why they should use your product rather than a competitive product, how do you answer?  Blatant claims of superiority or implied differentiation are the only way to convince them why your product should be used over another product.

What’s interesting is that when research and management talk about products to investors or in company presentations, especially before launch, they talk about and always answer questions about how the product is better than anything else out there, often using historical data from competitive products compared to their just released clinical data.  They highlight all the wonderful features and benefits that your product has over the competition, even quote data that imply superiority.

But, when marketing and sales wants to take those same messages to the market they have this regulatory issue.  While the research and management statements may be true,  they don’t necessarily come with the label claims or “substantial evidence” to support those same claims in advertising and promotion.  Yet, revenue forecasts are driven off those claims and expectations for differentiation.   And besides, who ever launched a product that wasn’t considered by their research team and management to be better than anything out there?

Pharmaceutical companies can no longer expect, pharmaceutical representatives to fill the label claim and “substantial evidence” data void for products.  The disconnect between product differentiation assumptions used for revenue forecasts and the regulatory constrained messaging puts the representative in an unfair position of having to deliver sales expectations beyond that which would be or ever could be achievable given a compliant presentation.

To be effective, even professional representatives need regulatory compliant information, comprehensive label claims, and more importantly, “substantial evidence” documented in peer-reviewed published literature.  This is the responsibility of management and the research team.  It is then marketing’s responsibility to develop forecasts that are aligned with the label claims and regulatory compliant information available for presentations and discussions by representatives.   mike@pharmareform.com

As word spreads and the popularity of Pharmaplasia increases so do the requests for more format options.  For those who have been waiting for the convenience of an e-book version of Pharmaplasia, it is now available as the Kindle Edition at Amazon.com ($9.99).

For industry insiders, Pharmaplasia provides a nostalgic look back at the changing pharmaceutical industry over the past five decades.  The book is packed with management and leadership lessons learned as industry veteran Mike Wokasch explores the root causes of mistakes and poor decisions that led to diminished trust and credibility and its current state of dysfunction.  With specific recommendations for change, Pharmaplasia answers many of the questions being asked about how pharmaceutical companies can increase R & D productivity; reduce operating expenses without sacrificing profitability, and what they should do to align with the evolving new healthcare market in light of healthcare reform.

“Wokasch’s insightful view of the pharmaceutical industry offers some logical explanations for the volatile changes and disappointment in that once proud business sector. As a senior level insider with access to key decision makers, Mike is able to provide both concrete examples and an educated perspective of the pinnacles and pitfalls surrounding this important segment of our economy and lives. This is a must read for both senior level pharma executives and those aspiring to bring back the real value to this once respected industry.” Jim Patchen

“(book) Came today and I read it straight thru. YES! I can certainly relate to the things you said in there! I just kept saying, how true, how true! ” C. Karabin

Order your  Kindle Edition of Pharmaplasia at Amazon.com

If we are trying to figure out how sales representatives can add value, we must start with those who will determine whether or not there is value being added… the customer.  This may be obvious to some, especially sales representatives, but over the past several decades pharmaceutical industry management has characterized the “value added” in the context of what sales representatives can do for the company or the product and not what sales representatives can do for the customer.  So let’s start with the customer (which is not just physicians in the evolving new healthcare market) and what their needs are and how we can add value by meeting or exceeding those expectations.

I don’t want to get off on a tangent but the needs and expectations I’m talking about here are not for things like lunches being delivered or a return of the tchotchkes.  Unfortunately, the industry trained physician offices into developing these expectations in lieu of meaningful clinical discussions about products.

So let’s review some of the evolving market expectations for pharmaceuticals that the industry must be ready to meet, especially in light of healthcare reform:

• Safe and effective products that can be differentiated (clinically proven and with label claims where possible) from currently available treatment options (including preventive medicines)
• A clear understanding with supportive data for the basic science behind the product, its mechanism of action, and rationale for efficacy and potential side effects and adverse reactions.
• Clinical data to support “comparative efficacy” and other claims of differentiation or even superiority (justify the premium pricing)
• Personalized medicine supported by biomarkers and companion diagnostics that can predict response, determine extent of response, and anticipate side effects and adverse reactions with specificity and accuracy
• Real world pharmacoeconomics data to support the economic value of the product and pricing that reflects the value being delivered. Again, justify the premium pricing.
• Hospitals will want data and methodologies to demonstrate the impact of products on newly established quality metrics and outcomes data that will be used to force rank their institution performance against national standards.

One of the first implications of meeting these more demanding market expectations is that pharmaceutical companies must readjust their thinking to be more selective in their pipeline evaluations and  a lot more comprehensive in their approach to research and development.  In the past, you could just find a compound, identify the potential indications for use, do the clinical studies, get approval, and go to market.  This traditional “get it to market” approach to R & D will deliver products and data that fall short of market expectations and hamper commercial viability of products in the evolving new healthcare market.

It also becomes apparent that regardless of the representative’s scientific or technical expertise, even the best of sales representatives will struggle to address these market expectations if the research foundation and data are lacking.  I believe this is one of the reasons sales representatives are struggling today.  Pharmaceutical research has not kept pace with the demands of the market and sales representatives are being asked to compensate for limited regulatory product labeling, a lack of product differentiation, and minimal real world clinical data that can be used in product discussions.

But let’s assume your company is committed to a much more comprehensive research approach to deliver truly innovative new products with robust data packages.  This has significant implications for how pharmaceutical sales representatives can add value for customers.   You might be surprised by some of the implications we’ll discuss in our next post.  mike@pharmareform.com

More often than not you hear Pharma defend high prescription drug prices as necessary to cover the high costs associated with pharmaceutical research and development.  Over the course of 7-10 years or longer they may spend $1.0 billion or more to get a product to market.  While the time and costs of drug development may be real, the rightfully skeptical healthcare market and patients have never really accepted this rationale for high prescription prices, often pointing to the more visible high cost of marketing and sales.  And now, this high cost of R & D rationale has become even less believable.

What makes this rationale even less believable today then ever before?  The fact that pharmaceutical companies can afford to spend tens of billions of dollars on mergers and acquisitions while dismantling the acquired companies, laying off thousands of employees (including research scientists), and at the same time, reducing the R & D investment the two merged companies might have otherwise spent.

The other area that challenges the credibility of the bogus high pricing rationale is the affordability pharmaceutical companies have to pay hundreds of millions of dollars or even billions of dollars in fines and settlements for alleged and sometimes proven wrongdoing.

Unfortunately, the billions of dollars spent on mega-mergers and litigation settlements don’t go towards producing any innovative new products.  Pfizer spent $68 billion (equal to the total annual amount of industry spending on R & D) to acquire Wyeth and Merck spent $41 billion to merge with Schering, not to mention the hundreds of millions spent by the two on restructuring, legal, and banking fees.  None of this money went to R & D.

Similarly, none of the $2.3 billion in fines and settlement Pfizer recently coughed up nor the hundreds of millions of dollars of settlement paid by other companies for their alleged indiscretions will go to R & D.   In fact, Pfizer’s $2.3 billion settlement represents more than 30% of their anticipated $6 billion spend on R& D this year.  The $2.3 billion alone would have put any other company in the top 20 of pharmaceutical companies in R & D spending.

So when Pharma says they need high prices to support R & D it is no surprise that the healthcare market and patients recoil with skepticism, frustration, and animosity.

mike@pharmareform.com