What can we do to increase efficiency?

THE STORY

"It's in the Label, so Surely I Can Say It."

OVERSTATEMENT OF EFFICACY

COMPARATIVE CLAIMS - Patient Compliance, Patient Preference, Patient Adherence

WHY FAIR BALANCE?

Reasonably Comparable

Patient Testimonials

Real World Evidence Standards: An Industry Call To Action

There is a plethora of important data in RWE. If we intend to use this data to support promotional claims, we must collectively, working with all involved parties, create standards to which we hold ourselves accountable. This is an imperative. Otherwise, the unintended consequences become a nightmare for all involved; our patients, their caregivers, their physicians, and for our business. We must do this to ensure use of this data is competent and reliable, benefits patients, is sustainable, minimizes litigation and Lanham Act suits, holds all companies to the same standards, and maintains industry credibility with all stakeholders.

This is hard, as there are a large number of challenging considerations to developing standards. Different groups are struggling to lead this. FDA is working daily to create regulatory standards. But this is also an industry opportunity. If we believe this data represents reliable information and that healthcare can rely on it, we must be willing to work to create robust, above reproach, data-driven standards to which we hold ourselves accountable. We have an opportunity to demonstrate our authentic commitment to advancing robust science and patient centricity. Now is the time.

Imagine a worse-case scenario. Imagine a mega database that can be evaluated in limitless ways. The company designs 200 exploratory searches to demonstrate drug A is better than drug B in patience adherence, tweaking different assumptions in each one. The programs run over night and the morning results show 5 scenarios that trend towards drug A outperforming drug B. The other 195 are either equivocal or show drug B better than drug A. That is unexpected, as the assumptions were deliberately chosen to give drug A the best possible results. However, as 5 of the scenarios showed drug A better, the company chooses to do further evaluation and eventually has the “best” study published in a reputable journal.

Clearly, this scenario raises numerous, important questions. What happens to all of the other data? No one outside the company will ever know that 95% of the studies came to a very different conclusion, nor that the scenarios were run based on selection-biased assumptions. How many patients might be harmed, either from lack of claimed effect, or delayed treatment with other proven products? How much unnecessary money will payers pay? What are the overall corporate compliance risks – product/payer litigation, DOJ investigation and subsequent fines, FDA enforcement, universal loss of credibility, loss of future research support, and damaged customer relationships, among many others.

No company representative reading this would ever condone such a scenario. But it illustrates some of the possibilities and reasons standards are an imperative. RWE standards are essential to ensure data confidence, optimal patient outcomes, and a “safe,” level playing field.

What should RWE standards address? I do not pretend to have all of the answers. The FDA is working daily on this. The Duke-Margolis Center for Health Policy is also leading this work, as are other groups. But, what is certain, is that we must find the will, and the leadership, to define and address those questions and create the standards by which we hold ourselves accountable. At a minimum, they must address both the data standards and definitions of the study design AND the appropriate context of presenting the information, with primary goals of producing scientifically sound data and minimizing bias, such as the following (NOT all inclusive):

1.    Study methodology and design adequacy, consistent with current, rigorous, scientific standards, designed to minimize bias

a.    Study intent/justification

b.    Areas of appropriate RWE usefulness

c.    Assumptions/endpoints selection appropriateness

d.    Data base (s) selection appropriateness and evaluation

e.    Inclusion criteria (patient demographics, disease severity, prior treatment, etc.)

f.     Data standard definitions (competent and reliable, for instance)

g.    Statistical considerations

h.    Control of variables

i.     Limitations of data

2.    Standards for data sharing must address the imperative for reducing the potential for bias, selection and otherwise

a.    Publication standards

                   i.    Study selection and transparency, including what is not published

                   ii.    Publication journal standards (or other publication type)

b.    Information dissemination – how, to whom and why

c.    Disclosure considerations

                     i.    Study design and limitations

                     ii.    Additional needed studies

  iii.    Relevant information from other studies, including differing conclusions

                    iv.    Author/researcher relationships with study supporter

                     v.    Inconsistencies with product labeling

In addition to the above minimal considerations, process and structure are imperatives to ensure consistency and accountability. For instance, as thought-starters:

1.    Should the standards also create a standardized template for presenting RWE, such as the one developed for sharing clinical trial information on CT.gov? The template could potentially help minimize discretion and variability in the application of the standards.

2.    How does this get memorialized and enforced? Should the industry, working with a broad group of stakeholders, such as Duke-Margolis and/or other nonprofit centers, create an industry code focused on RWE?

3.    Should the standards encourage the development of corporate internal processes, and perhaps provide examples, for ensuring that appropriate standards are applied to company communications involving RWE? For example, is additional rigorous scientific input required for RWE, even beyond the current standard promotional review committee structure?

Our industry, as one of the primary consumers of this data, has both a right, and a responsibility to help lead the development of the highest quality RWE standards. And, we have a responsibility to ensure the data is consistently of a scientifically sound standard and is developed and shared in an unbiased way. If we can’t create (and follow) consistent, data-driven standards - if it is too difficult - we must ask ourselves the obvious. Should we be using that data in promotion?

Truth or truth?

Almost two years ago, I published the article below. Please take a moment and refresh yourself with the points in that one prior to reading these additional thoughts, as that is an important piece of context.

I am constantly struck by the irony of how rapidly some things change, while simultaneously seemingly to never change. This concept of "off-label" promotion was the topic du jour then in our industry, as it remains today. In my 2016 article, I looked at this from the perspective of whether or not something is misleading and suggested some applicable tests from a review/confidence standpoint. Since that time, the FDA has issued a draft guidance clarifying some of these questions from their point of view. However, the question remains. What do we want to do?

As we continue to consider promotional claim support in all of the contexts discussed in the previous article, I think it is vital to also approach this from a "Truthful/truthful" perspective, as we consistently use that term in a definitive way as it is the ultimate test for our ability to promote a prescription drug claim. As the regulations allow, if a claim is truthful (and not misleading), we may promote it. The regulatory test for supporting a claim, after all, is that the claim must be truthful and not misleading.

So, my question. What is truthful in science? Truth in science is somewhat of a slippery slope, as just when we think we know the truth, we are often surprised. The "definitive" study is replaced, and contradicted by, another "definitive" study. And, to what standard of truthfulness should we hold ourselves when patients lives and health are at stake, regardless of what might pass the regulatory test?

As one would imagine, there are numerous definitions and thoughts on the most appropriate definition of truth and there are arguments on all sides for their appropriateness. I can only imagine the incredible conversations among the great philosophers! For our purposes, though, I will simplify and use just two of those thoughts with a little license of my own.

First, truth with a small "t." To me, the small "t" truth is the fact that we are accurately reporting what the study says. That, taking one approach, is truthful. However, as I said in my article below, does that study publication take into account all aspects of the study? Does it draw conclusions that the data does not support? Even using the small "t" truth, there may be some serious omissions, inaccurate conclusions, and ultimately, inappropriate drug use. Certainly, the FDA draft guidance addresses many of these questions from their perspective, though a final guidance has not been published and will only happen with much external input and deliberation.

Now, Truth with a capital "T." Even if the study data and publication pass all rigorous statistical tests, and even if we include appropriate disclosures/disclaimers, how confident are we that the study is definitive and robust enough to support a solid definition of scientific truth when considering the entire environment and complete evidence? Considering data has to first pass the definition of "truth" to support a claim, how do we represent this appropriately in the overall context of truthful and not be misleading? Does a disclaimer really clarify the overall importance (or not) of the data? Might a disclaimer actually make something Truthful? Even if so, have we objectively tested our assumption that the disclaimer works as we believe it does? How do we know when the overall data is robust enough and where the tipping point is for Truthful?

My goal here is to be provocative. There are no bright lines and there are many views. And, much of the question lies as much in the promotional approach and language as it does in the data itself. Take a few minutes and contemplate these thoughts, as well as those in the original article about our imperative to contemplate other legal and competitive considerations for our own business reasons. I am certain we all agree on this: The patients we serve deserve the most honest, authentic, complete, emotionally and business-neutral evidence and presentation as possible. To that end, the question is not only, what is the data standard the government and the environment require of us? The real question is, how do we define our industry standard of Truth?

Want to explore more? Visit our website at www.lucyroseandassociates.com

The Innovation Imperative

Innovate or become obsolete. This is especially true in the healthcare industry generally, and in the pharmaceutical/biologics industries specifically. The industry must urgently innovate relative to how it defines itself in a rapidly changing healthcare ecosystem. Individual companies must either aggressively innovate or risk falling behind on a daily basis. Though not everyone agrees on how to do so, everyone does agree on one thing - the time is now.

I was asked numerous times last week what I thought companies should consider while working to create a sustainable future in a morphing environment. For instance, how does the industry as a whole, and the companies working in it, create ideal environments and solutions for issues such as: payer and systems data needs and pricing challenges, metadata use, personalized medicine demands, pricing challenges, globalization, responsibility/ownership continuum for new product development, quality challenges, patent expirations, demands for meaningful clinical differentiation and higher (not lower) quality data, interactions with patients, commercialization, compliance challenges, industry perception, etc.

I do not pretend to have all the answers to these extraordinary challenges. The answers will be ever evolving, and will involve working at the tree AND forest level. We must think of healthcare in the broadest sense, using a wide-angle lens, not simply as drugs and devices - much like it is important to think of transportation as a whole, not just the train system. But I did spend some time contemplating this question last week, and in the spirit of strategic innovation, offer the following three strategies. They are not all-inclusive, but are intended to scratch this very rough surface. But, as with anything intended as a game changer, you have start somewhere.           

1.    Create a culture that demands innovation as an imperative at every level and rewards, embraces, and requires constant improvement.  Every company’s mantra should be, “THE STATUS QUO IS NEVER GOOD ENOUGH.”

According to David Champion in the Harvard Business Review (January 26, 2009), as long ago as 2009, “One Pennsylvania hospital, for example, was able to reduce infections caused by inserting catheters into a patient’s bloodstream from 37 occurrences to just six. Deaths from infections fell from 19 to one. The hospital also saved $1.4 million a year in the direct costs related to treating the infections. Achieving all this required virtually no investment, just six simple changes in procedure, such as requiring staff to completely remove faulty catheters and insert new ones rather than attempt to fix the faulty catheter.”

• a.    Hire employees based on their ability to innovate and foster innovation, develop them to be even more innovative, reward them for their innovation at every opportunity. Do not allow the old thinking of hiring based only on previous specific job experience to be the primary driver. Look for new ideas and for complimentary skills and strengths. Use hiring as an opportunity to infuse fresh thinking, whether hiring from within the company or outside. Insist on building a widely diverse workforce to enhance innovation.
• b.    Reward innovation in every department, every process, every small “win”, not just the major breakthroughs.  Ask every day, “How can we improve anything/everything by doing it better, differently, or not at all?”
• c.     Recognize that seemingly small improvements, even small process improvements, can create huge breakthroughs. Relentlessly search for these opportunities.
• d.    Determinedly scan the environment for new opportunities, innovations that you might leverage and improve upon, and futuristic business intelligence.
• e.    Make proactive listening, internally and externally, a cultural imperative. Constantly create opportunities for listening. Listen to learn and understand, not to respond or verify a preconceived idea. Listen, Listen, Listen.

2.    Commit to developing and commercializing truly innovative, medically critical, differentiated products with higher quality, value-driven data. The healthcare ecosystem is demanding it.

As Novo Nordisk CEO, Lars Rebien Sørensen, recently told Bloomberg TV, “The next line of products have to have an even greater height of innovation, which means those that do not have that height of innovation will have to be culled. We need to be innovative. Otherwise, it’s going to be difficult for us to get reimbursement for our drugs. Me-too or me-better drugs will not be good enough in the future and hence we need to prioritize.”

• a.    Develop products, recognizing all data needs, using “backwards planning.” In other words, develop products to demonstrate identified/desired information for approval, promotion and reimbursement.
• b.    Develop products that are clinically innovative, solve authentic medical challenges, and create demonstrable clinical value, not just variations of established products.
• c.     Commit resources to create high-quality data that address real value concerns to meet global payer and system expectations. Create these additional resources by decreasing the number of smaller, lesser quality studies that do not meet ecosystem expectations or requirements.
• d.    Evaluate possible mergers and acquisitions (and product acquisition) objectively with an expectation consistent with this commitment to high quality, innovative assets. Use multi-disciplinary teams for due diligence to honestly and openly evaluate for business success under this rubric, not simply to support an a priori decision to purchase.

3.    Change marketing incentive payment and expectations from revenue-based to profit-based. Perhaps the most difficult, it takes true business commitment and cultural change to make this happen. But, especially in light of drug pricing scrutiny, the need for targeted focus to increase profits is essential. It is easier to do this on the business/marketing side than on the sales side, as sales has less control of profitability variables. But, moving boldly moving in this direction, would:

• a.    Increase return on investment, through driving more careful targeting, planning, resource deployment, market understanding (especially payers and systems), promotional expenditures, and value-based focus.
• b.    Create a culture of vigorous authentic listening and questioning with all stakeholders throughout the asset’s life cycle, resulting in a clearer understanding of needs and more focused and effective programming.
• c.     Increase the quality, impact, and longevity of promotional materials and programs, while also increasing the quality of promotional execution and the alignment with compliance requirements
• d.     Decrease the volume of ineffective materials and programs, thereby preserving resources for more impactful promotion and increased clinical studies quality. 
• e.    Create vertical business data transparency and marketing alignment with overall business success measurements.

Healthcare delivery is changing at heightened speed. Consider recent innovation breakthroughs, such as - 3D printing, CRISPR, robotic surgeons, needle free dentistry, remote patient monitoring, prosthetic advances, health informatics, and light bulbs that disinfect and kill bacteria, to name a few. This is a defining moment for the healthcare industry. The question is not just one of relevance. More importantly, how does the industry define and structure itself to lead meaningful change that significantly, and authentically, contributes positively to the dynamic healthcare system?

Sharing Safety: A Patient, and Business, Imperative

Sharing vital safety information in promotional materials and sales representative presentations isn’t just required by law and regulation, it is an undeniable imperative for both patient and commercial success.

So why is minimizing it, or even omitting it, still the most common violation OPDP cites in enforcement letters? The answer I continue to hear most often is, “we need more room for efficacy claims, even at the expense of sharing the safety information.” Highly successful commercial professionals know better.

Acknowledging the obvious need to share efficacy information, sharing important and understandable safety is the most important aspect of overall commercial success. To maximize its success, it should also be relevant, timely, and integrated deeply into the product’s “story.” Consider the three reasons below:

1. The patients who take a medical product must fully understand the breadth of the treatment, both the efficacy and the safety, to maximize the benefit and improve their health. Patients who fully understand the benefits AND safety are more likely to stay on the product, thus increasing adherence and compliance. It is critical that they have appropriate knowledge and expectations in order to ensure successful treatment. To provide such is an indication of our authenticity regarding true patient centricity. And as we are in the business of improving patient health, a successfully treated patient is our best advocate for our product.
2. It is in our business best interest to also boldly share, and consistently reinforce, the safety profile of our products with health care providers – not because we have to, but because doing so creates the best opportunity for commercial success. Health care providers know all treatments may cause adverse events, thus we must share the safety to create credibility. Even more importantly, though, is that we must share the safety to enable appropriate patient selection, create appropriate expectations, and encourage appropriate use. It may take a sales representative 7-12 interactions to influence a health care provider to prescribe a new product, but it will take just a couple of unexpected middle of the night patient complaints to cause the provider to return to a previous treatment regimen. Sharing safety in an honest and transparent way creates win-wins for the patient, the health care provider, and the company’s bottom line.
3. We must share safety in a way that satisfies today’s legal liability environment, as well as the FDA regulations. When sharing safety, it is vital to consider both the content and the prominence. Here is the link to the FDA draft guidance on safety content and presentation for your reference.

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM155480.pdf

There are still many unanswered questions regarding safety presentation, such as patient recall and comprehension in TV ads, ideal amount of necessary information (without also scaring otherwise appropriate patients from even trying the product), and how to best provide the information in various media. Those challenges still need to be addressed and are valid concerns.

However, one thing is certain. Sharing appropriate safety should not be hidden below a sight line, lost in contrast, placed at the bottom of the ad in paragraph form with no header, left by a sales representative until the end of the presentation when it is clear they will not be able to share it, or especially omitted entirely. In addition to sharing appropriate content, it is an imperative to share safety with prominence reasonably comparable to the efficacy presentation.

Ensuring that health care providers and patients know what to expect from their treatment, both the benefits and the safety, is in the best interest of the patient and the best commercial interest of the company. A patient who stops taking a treatment due to unexpected adverse events will never benefit from its efficacy, yielding the worst outcome for everyone.

Forethought Wins: Strategically Assessing Promotion in a Post-Amarin Ecosystem

Pharmaceutical and biologic companies are evaluating recent court outcomes (such as the Amarin and Pacira cases) on promoting off label (or expanded or subpopulations) use, using other than the historical interpretation of substantial evidence data. As companies are determining their promotional path forward, they are taking into account the continued requirement to promote in a truthful and non-misleading way, as well as the use of disclaimers. Clearly, there is an industry interest to distribute these data.

However, as companies are evaluating these cases and their interest in data use/distribution decisions, it is also imperative to consider the possible long-term consequences of these decisions.

The following considerations are not all inclusive, but are some of those that must be contemplated as part of on-going deliberations:

1. Liability considerations – Will the type, level, and quality of data the company shares proactively put it at greater risk for liability challenges? If so, is the company willing and able to defend these suits?

1. Competitive considerations – As the FDA is taking substantially fewer promotional enforcement actions, is the company prepared, both from a will and resource perspective, to handle competitive promotional challenges? Is the company prepared to bring, and defend, Lanham Act suits? Will the company hold itself and competitors to the same data standard, and how will that be defined?

1. Payer considerations – At a time when payers are expecting higher quality data, including comparative data, will the quality of data the company provides meet these expectations? What are our expectations for our company’s competitor’s data quality? What internal requirements do we create for promotional data and how do we create executional uniformity?

1. Additional Governmental Agency considerations – What is the company’s overall marketing strategy, and how might other agencies (such as the DOJ, SEC, OIG, and the states) view this use of/distribution of data in the overall promotional context?

1. Reputation considerations - How important is the company’s reputation with stakeholders? Will the company’s (and product’s) reputation be harmed by the promotional decision?

1. Millennial authenticity considerations – Understanding data regarding Millennial promotional expectations, such as authenticity and transparency, will the company’s overall strategy for communicating this data build trust and long-term support with Millennials? If not, what are the long-term consequences for alienating the Millennial consumer base?

The decisions surrounding product promotion, and the evidence required to do so, are challenging for all companies. Each company must carefully consider not only short-term potential gains, but also fully assess possibly damaging long-term consequences.