Conducted across 46 states and with a group of 400 respondents, the sample was representative of just how many nurse practitioners, physician’s assistants, clinical nurse specialists and certified nurse midwives there are in the US. The demand for NPPs is leading to higher pay and an increased respect within the payer community. Aetna now considers nurse practitioners, for example, to be primary care providers and reimburses them for their services thusly.

When considering what influenced their behavior as prescribers the most, the survey found that NPPs tend to consider efficacy, their experiences with the drug, and price, in that order. As 82% of the respondents indicated they had no restrictions when dealing with sales representatives (17% had certain restrictions, and 11% said they were completely restricted), and that most respondents were open to support from them, why have sales reps and pharma by and large neglected to address this demographic?

Brenda Rizzo, author of the report and an advanced practice nurse herself, says sales reps make calls “based upon prescribing behaviors, and on that basis alone, NPPs are pretty much invisible.” Misconceptions about NPPs abound, according to the report, including that they prescribe based on a protocol set by their physician practice partners, that if they have the ability to prescribe, they rarely do, or that they are simply refilling prescriptions that have already been decided on by a physician. Pharma “doesn’t realize that this is an audience that makes independent prescribing decisions, and that having the right information to make those decisions is incumbent on pharma companies; to provide it to non-physician prescribers is equally important as it is to provide that information to physicians,” emphasizes Rizzo.

So what kind of information do non-physician prescribers want? As a group shown to be active attendees of national conferences and maintaining exchange of advice among colleagues and fellow professionals, first and foremost the information should be sharable and accurate to provide trustworthy resources that can further facilitate dialogue and be spread easily. Secondly, NPPs listed printed education materials from pharmaceutical companies as one of their top-rated tools when looking to improve patient compliance. More specifically, 61.3% of respondents, when asked about what kind of support they’d expect from pharma companies, said “Education about the pharmaceutical drug or medical device directed to the NPP for the patient,” 54.5% responded “Disease state information to educate the patient.” and 51.5% said “Assessment tools to help identify problems that can be addressed.”

NPPs, as this study shows, not only want to engage, but expect valuable engagement tools from pharma to help make their jobs easier. With primary care taking on a new definition that includes long-term, patient-focused care, the physician’s ability to orchestrate outcomes is increasingly being diluted and in need of help from nurse practitioners, physician’s assistants and other NPPs. As such, pharma needs to keep a keen eye on these providers: payers, private practices, and health care facilities have already gotten the memo.

As you look over the last 12 years of CBI conferences, a phrase relevant to this business issue comes to mind: “If at first you do not succeed, try, try again.”  For those of us engaged in this work, we know the challenges, results and skepticism from more than a decade of experience.  How do we ensure adequate funding and measurement of programs, to prove that program ROI is possible?  To do this requires support of senior leadership from your company or your client.

In 1984, I developed a patient adherence program with a chain drug store, to demonstrate the ROI.  We tracked the impact this program had on prescription refill lift.  The 6-month pilot showed a 2 to 1 ROI, in terms of test versus control.  However, our senior leadership did not support a larger program implementation, as the pharmacist at the store level was difficult to engage.  This is changing with recent initiatives, where scripts used by pharmacists, at first fills, are resulting in 38%+ refill persistence over 6-12 months.  Additionally, many chain drug stores have developed smart phone apps that automate adherence reminders and simplify prescription refill, with a 5 to 1 ROI.  So, guided interactions and technologies may to help solve this industry problem at very little additional cost.

There continues to be broad acceptance that medication adherence is a problem and that the industry stands to benefit the most from its implementation.  What is most needed is the continuous presence of adherence in the brand strategic plan.  We believe that, along with senior level commitment, this is the primary barrier to resolving the problem.  Why?  Without a plan based on evidence for what works, vendor tactics drive brand strategy in this area.  And, without experience with this planning, skill sets will not develop and be rewarded.  One top 5 pharma company has had 4-5 task forces/leaders of medication adherence in this past 12 year time frame, without changes in corporate policies and procedures to integrate and institutionalize programming to ensure revenue generation.  Perhaps this is one reason that some companies are looking outward, to a value based contracting model, to help solve the adherence challenge.  So, there is innovation and determination, but without the commitment of senior management, this issue cannot be solved.

The April 2013 CBI Patient Adherence and Support Summit (PASS), and the Strategic Patient Adherence (SPA) Awards, will highlight companies and initiatives where corporate and brand strategies have provided the ROI needed to make patient adherence an integral part of business.  I hope to see you at the conference this month.

Niels Erik Hansen, president and CEO of Intelligent Hospital Systems

Last fall’s deadly meningitis outbreak linked to contaminated steroid injections is a tragic reminder of the risk of errors inherent in manual pharmacy medication compounding. Unsanitary conditions at the Massachusetts compounding pharmacy that made the injections resulted in fungal contamination of the drugs. The resulting outbreak sickened nearly 700 people in 19 states, and killed more than 40. Can technology prevent another outbreak?

Although the Massachusetts case is an egregious example of medication compounding gone awry, it is hardly an isolated incident. In December, the journal American Health & Drug Benefits reported that medication errors from injectable drugs harm more than 1 million patients annually in US hospitals. Adverse events due to injectable medications cost US healthcare payers between $2.7 billion to $5.1 billion annually, an average of $600,000 per hospital.

If a contagious disease with such devastating consequences and costs were to emerge, we would put all available resources toward eradicating it. Yet this epidemic of medication errors goes largely unchallenged. What is perhaps most tragic is that the technology to prevent it is already available. Automated pharmacy compounding systems have existed for more than a decade – it’s just that too few pharmacies use them.

Medication compounding is a common practice in hospitals and pharmacies. Physicians prescribe combinations of medicines that are mixed in a single syringe or IV bag for a specific patient. To make these compounds accurately and safely, pharmacists must measure and combine drugs with meticulous care – for example, diluting a few milliliters of one drug and adding an equally small quantity of another. But despite the best efforts of pharmacy workers to mix medications perfectly, humans are not perfect.

One of the biggest advantages automated pharmacy compounding technology provides is removing the primary source of contamination and error – humans – from the compounding process. And automated compounding systems deliver many more benefits than the ability to make highly-precise sterile compounds exactly right every time.

Automated compounders have an aseptic chamber where medications are mixed. Vials are photographed and their barcodes are scanned; both are then matched to a product database to ensure the right product is being used in each step. As compounding progresses, pulsed UV light provides extra disinfection to critical puncture sites, needles are automatically capped (reducing the risk of needle sticks), and the finished product is dispensed in a syringe or IV bag with an electronic barcode label for documentation. The result is a sterile and accurate medication compound that is verifiably safe for the patient.

By increasing safety, the technology also saves money. Automation lowers the cost-per-dose of medication and reduces the need for medication outsourcing. Equally important, automated compounding minimizes the risk of medication errors that can result in patient injury, emergency intervention, extended hospitalizations and tort liability – critical considerations for hospitals already burdened with more than a half-million dollars in costs from adverse drug events every year.

Some will say that automated compounding systems are expensive, but that’s relative. CT scanners, MRI machines and many other types of healthcare technology can be considered expensive, but they are an investment in a higher standard of patient care. Fortunately, through enhanced safety and lower medication costs, even the most expensive automated compounding systems have paid for themselves in less than three years.

Last fall following the meningitis outbreak, Congress held hearings about how the FDA can better regulate compounding pharmacies. Rep. Ed Markey (D-MA) introduced legislation to enhance pharmacy safety, and plans to reintroduce it in the new Congress. It is imperative that any effort to regulate pharmacy compounding include a discussion of the available technology that is proven to make it safer. Congress and the FDA must seize this opportunity to put medical technology to its highest and best use, not just improving the quality of patients’ lives, but saving them.

Dr. Niels Erik Hansen is president and CEO of Intelligent Hospital Systems in Winnipeg.

Epigenetics is the study of changes in human gene expression, in particular from environmental factors.  Pharma is also experiencing epigenetic change.  Human genes are formed from DNA, which are instructions much like a blueprint.  Similarly, the environment is changing pharmaceutical DNA and how brand marketing is instructed.

For example, pharma’s genetic dependence on traditional blueprints (and standard agency recipes), targeting revenue from new molecules in the pipeline, is no longer sufficient for survival.  The environment has limited the availability of new blockbuster brands.

Similarly, the environment is changing the DNA of our belief systems. Here I am speaking of the evidence for effectiveness of patient medication adherence interventions.  How is this changing the DNA of brand marketing?

For more than a decade, we have believed that medication non-adherence was the result of patient knowledge and capabilities.  This has driven marketing focused on “patient education”, “segmentation” to identify profiles of patients based on their “barriers” (or “deficits”) and “tailoring” to help customize needed changes in the foregoing.

We have assumed that patient knowledge, of their disease and treatment, and their health literacy capabilities, for example, are critical to patient adherence.

However, the evidence now tells us that our assumptions were wrong.  More than 100 published studies show no correlation between a patient’s level of knowledge of their disease and treatment, and medication adherence.  How many valid studies show a correlation?  None of which I am aware.  Studies have shown that patient knowledge can be increased, but no increase in medication adherence has resulted.

Similarly, recent systematic reviews show no evidence that health literacy is associated with medication adherence in adult or pediatric populations.  As one of these review papers summarizes:

“A critical element of successful self-management is medication adherence. On this front, the evidence has been mixed. Although patients with limited literacy have more trouble understanding primary and precautionary medication label instructions and are less likely to be able to report the name of their medication, there is no consistent finding of worse medication adherence among patients with limited literacy.”

In fact, there is evidence that patients with “adequate health literacy are more inclined to purposefully not adhere to their discharge instructions.”

Do health literacy interventions improve adherence?  A 2011 systematic review found no evidence.

What about the promotion of health literacy programs?  Again, a 2011 review reports:

“…current research on health promotion for participants with low health literacy provides insufficient information to conclude whether interventions for health literacy can attract the target population, achieve an effect that is sustainable, or be generalized outside of clinical settings.”

“Tailoring” messaging based on patient characteristics has been a proposed as a solution to patient barriers.  However, a 2012 review paper, on the efficacy of tailored interventions for self-management outcomes of type 2 diabetes, hypertension or heart disease, concluded:

“Tailored interventions had no impact on self-management activities such as medication adherence, self-monitoring, exercise, smoking, or diet control.”

So, there is no peer-reviewed evidence to support developing pharma marketing strategy or tactics based on these assumptions of patient deficits.  Money spent in interventions based on these beliefs will produce limited or no ROI, as industry cost-effectiveness evaluations show.

What does the evidence, both academic and industry, show improves medication adherence?  This will be part of what you will hear at the Keynote Panel Discussion at CBI’s Patient Adherence and Support Summit (PASS) on Monday, April 29^th in Philadelphia.  I look forward to seeing you there.

Grant Corbett is principal at Behavior Change Solutions, Inc. He can be reached at grant.corbett@behavior-change-solutions.com.

The line between physician marketing and consumer marketing has blurred as the facets of a brand campaign – from disease and drug-mechanism education to efficacy, safety and lifestyle claims – dovetail across the traditional physician-patient separation.

“We know that DTC advertising is often the catalyst for patients initiating conversations with their physicians about their untreated or undertreated conditions,” wrote Janet Woodcock, director of the Center for Drug Evaluation and Research, in an email on the changes. “The decision to restructure the divisions reflects our commitment to continue providing close oversight of DTC advertising.”

Before it got upgraded to a “Super Office” in 2011, OPDP was fondly (or sometimes not so fondly) called DDMAC (dee dee mac), which stood for the Division of Drug Marketing, Advertising and Communications. When DDMAC turned into OPDP, the office was split into two divisions: the Division of Consumer Drug Promotion, and the Division of Professional Drug Promotion. As OPDP, the steady stream of warning and untitled letters continued unabated, mostly chastising pharma marketers for misbranding, off-label, overstating the efficacy or minimizing the risks of a product, or the misuse of a color scheme, in one famous educational piece created for Novartis.

With today’s announcement, ODPD, pending final review, will rename its two primary divisions. They will now be called the Division of Advertising and Promotion Review I, and the Division of Advertising and Promotion Review II. Review of promotional materials will be separated and organized by therapeutic class, not by professional or consumer. “ODPP concluded that a structure that integrates the review of health care professional-directed and consumer directed promotion across the two divisions” would meet the stated goals of increasing efficiency, improving work distribution, and eliminating redundancy, wrote Woodcock.

“Our ODPD reviewers will continue to use a comprehensive surveillance, enforcement, and education program to foster superior communication of labeling and promotional information to both health care professionals and consumers,” she wrote.

Tom Abrams remains head of ODPD. For a list of the new review groups categorized by therapeutic area, click here.

Falsified and substandard medicines can be ineffective, promote drug resistance and even cause severe illness and death, said panel chairman Lawrence Gostin, Georgetown University Law Center professor and director of the WHO Collaborating Center on Public Health Law and Human Rights. The report [“Countering the Problem of Falsified and Substandard Drugs” available at www.nap.edu] urged regulators to adopt international practices on surveillance, regulation and enforcement, including technical quality standards developed by the International Conference on Harmonization.

Most important to pharma companies, the panel backed a mandatory U.S. electronic drug track-and-trace system able to identify products at the unit level through unique serial numbers. This approach is supported by the Food and Drug Administration – which requested the report — but considered too costly and complex by manufacturers, pharmacists and wholesalers.

The expert panel also proposed to strengthen supply chain tracking through tighter state regulation of drug wholesalers, including creation of a public database of distribution firms that have had licenses suspended or revoked. And the federal government would help low- and middle-income countries detect substandard products by identifying new sampling and analytical technologies through a central repository at the National Institute of Standards and  Technology (NIST).

Counterfeits separate

One strategy for building support for all these activities is the panel’s decision to drop the term “counterfeit” in describing substandard drugs that pose a public health risk. The aim is to narrow the use of “counterfeit” to refer to products that infringe on trademarks and intellectual property protections, but are not necessarily substandard or adulterated. Calling all poor quality drugs “counterfeit,” the report notes, is seen by advocates for generic and low-cost medicines as a way to use the campaign against “bad drugs” as a guise to enforce patent and trademark regulations.

Similarly, the report  defines more clearly “substandard,” “falsified” and “unregistered” drugs to provide a basis for regulatory agencies to target their legal and regulatory efforts.

The panel also calls for international development and financing agencies to support drug manufacturers in low-income countries that seek to upgrade facilities to meet good manufacturing practices. Such investment efforts would counter fake drug marketing by boosting local capacity for producing quality medicines.

Although an international treaty enforcing drug quality standards is the ultimate goal, publication of guidance on best practices as an interim step “is more realistic,” noted panel member Hans Hogerzeil, professor of global health at Groningen University in the Netherlands. The IOM panel also is asking the World Health Assembly to support its basic recommendations at its May 2013 annual meeting.

There’s some optimism that this report may spur FDA, manufacturers, distributors and pharmacists to reach agreement on an effective drug track-and-track system, an issue that has generated heated debate for more than a decade. Congressional action is needed to authorize mandatory tracking, as well as to require states to support a database on licensed drug wholesalers. Added resources for FDA to take on these tasks also is a real challenge.

While cost is an issue everywhere in implementing new regulatory and oversight programs, Gostin noted that limiting the use of substandard drugs would bring notable benefits in terms of lower hospital costs and fewer drug-resistant medicines. Adopting the panel’s recommendations, he said, is “a very good investment.”

The commentary included in the law echoes industry concern that more clarity is needed to ensure that preemption is not applied ‘too narrowly’. While the law may not be the best news for pharma, “it’s better to have one burdensome statute than to have 50 different ones with variable impacts; a statute that at least imposes  uniformity across states has value,” as John Kamp, Executive Director for the Coalition for Healthcare Communication put it to Pharm Exec. CMS responded to the issue by promising guidelines to clarify the preemption requirements, while at the same time adding a confusing caveat that state preemptions would be evaluated on a case-by-case basis. Kamp warns, “This case-by-case clause is a flag to industry that says, ‘This may not be over’.” Such a contingency gives the CMS the flexibility to gauge how Federal Reporting actually works and then to adjust its actions accordingly, versus simply living with the reality of what States currently do in their own reporting.

Alternatively, The Sunshine Act may have the effect of doing away with the clash that state laws present against the status quo in Washington. In January, Minnesota repealed its physician payment disclosure laws in anticipation of the Sunshine Act’s release. “There’s an element of logic that dictates states will fall back on the federal statute and reinforce the complexity of Sunshine as it is,” says Saul B. Helman MD, Managing Director and Life Sciences segment leader at Navigant Consulting, a company that advises life science companies on issues of compliance.

“On the other hand,” he counters, “states may realize that they require disclosure for payments that are not included in the federal Act, or that they may require different thresholds and additional areas of reporting.” For instance, if a state decides that CMS’ defined list of teaching hospitals fails to include facilities that that state’s government pays for to provide services, more specifically the prescribing of medical products, it may prompt further requirements to be introduced. As Helman puts it, there’s an ambiguous ‘wait and see’ period as to how states will respond on this issue.

The bottom line is that compliance remains a dynamic area, especially with the possibility of stepped up international requirements being introduced to the mix in the future.  For now, the Act urges that companies continue to comply with state and local authorities in their reporting requirements until August 1st, when the federal requirements take effect.

In addition to taking a close look at pharma’s internal processes, manufacturing facilities and corporate policies this year, the US Justice Department (DOJ) – in the name of “protecting consumers where they are most vulnerable,” according to Frimpong – is also placing a “focus on people,” since processes and policies (at least publicly-circulated processes and policies) don’t typically break the law; people do. “We know there are enormous cost pressures, but you can’t sacrifice safety under these pressures,” said Frimpong.

To that end, Frimpong recommended that attendees ask themselves five questions about the group of people they work with, to help identify potential problems before they result in an investigation or worse. In summary, Frimpong’s questions are:

1. Do we have the right people? Are they experts in their specific task areas? “People are not fungible,” said Frimpong. Given the complexity involved in certain manufacturing practices, for example, it’s crucial that the right person is working in the right role.

2. Do our people have the right incentives enabling them to see problems, report problems, and fix problems? Frimpong said strong internal communications are key to facilitating diligent compliance programs.

3. Are our people satisfied and engaged with the company and their jobs? Frimpong said the departure of key people can sometimes lead to lapses in compliance, citing SB Pharmaco, a GSK subsidiary, and the manufacturing deficiencies at the company’s (now-closed) plant in Cidra, Puerto Rico.

4. Are people and policies working in harmony? Companies should set realistic goals, and refrain from crafting compliance programs and procedures that can’t be met. Unrealistic standards are doomed to fail, said Frimpong.

5. Do we, as chief compliance officers, know what our people are actually doing? Given the size and scope of many large, multinational pharmas, it’s important that leadership make a concerted effort to communicate with and assess the performance of specific individuals whenever possible.

Frimpong underscored the problem – and gave examples – of companies who’ve put patients in harm’s way in service of the bottom line, saying, “when companies put profits over patients, everyone loses.”

Extra: For a report from Jill Wechsler on comments about the recent Caronia decision made by Tom Abrams, director of the Office of Prescription Drug Promotion, at the CBI Congress, click here.

The approvals also show that the US continues to outpace Europe and Canada in approving new medicines, as the FDA works to speed up its application processes. This comes at a time when the EMA is putting more emphasis on reviewing medicines already on the market, bowing to government pressures to take the concept of value more seriously and to reduce wasteful health expenditures. Conversely, the fifth installment of PDUFA has given the FDA more resources to apply to the task of improvng the registration timeline.

According to Raghuram Selvaraju, head of healthcare equity research at Aegis Capital Corp, another reason FDA has pushed up the pace is industry ”beating Margaret Hamburg over the head” with complaints about review cycle delays, general disorganization and a level of risk aversion not commensurate with a drug’s potential benefit for patients. “The good news is that drugs that should get approved have been getting approved without delay, and in some cases, if the evidence is really overwhelming…ahead of the PDUFA date.” In its most recent effort to spur approval, the agency also issued guidance by which companies can more effectively demonstrate clinical value to their drugs by eliminating certain patients from trials.

Another explanation behind the approval uptick has been a steady increase in biologics brought to market. This increase highlights the growing familiarity the FDA has gained with such medicines and the sophisticated science behind them. But the best news of all is that drugs approved this year, in addressing real medical needs yet to be met, reaffirm that patients are still important to the industry.

Warm and fuzzy notions aside, it will be interesting to see how sequestration affects drug approvals in the year to come.  The question:  how will the FDA manage expectations to keep up this good pace of approvals when sequestration carries a mandate to cut the agency’s funding by $318 million?

What is strictly legal in the context of sales and marketing practices, working with government officials in global markets, and running and reporting on clinical programs, may not always be the last word on how a company should act in these areas. In other words, companies often need to go beyond adherence to the letter of the law, and instead consider the broader implications of specific conduct, before a decision is made, or a policy developed.

As the role and function of compliance teams grows within pharma companies, different approaches to the law, and what it should look like in practice, can differ, which sometimes pits internal lawyers against one another. “Compliance wants to truly ferret out any wrongdoing that’s going on – that’s not to say legal doesn’t – but compliance wants to expose it,” says Tim Ayers, VP, chief compliance officer, at Dendreon, a biotech focused on cancer therapies. “Legal wants to wrap everything under privilege, not to hide things, but to deal with things from a very legal, mitigating risk perspective, whereas compliance wants to come in and say, ‘Listen, this is what we’ve done, let’s fix it.’”

Companies operating under a corporate integrity agreement (CIA) by necessity have elevated compliance officers to the c-suite, but in other companies that haven’t had to deal with Office of Inspector General (OIG) or Department of Justice (DOJ) investigations – and there aren’t many of these left – compliance teams are sometimes subordinate to legal departments, even though the members of both groups hold law degrees. It’s in the application of the law, where the hairs get split. “Legal likes to ask very narrowly tailored questions, specific to the legal issue,” says Ayers. “And it might be perfectly sound legal advice, but it might not make sense from a compliance perspective, at forty-thousand feet.”

So what is the right organizational structure for compliance teams, and the chief compliance officer? “I used to be of the opinion that it all depends on the company’s evolution and lifecycle,” says Ayers, who was formerly associate general counsel and executive director of compliance at Seattle Genetics, and who has also served as general counsel at Allos Therapeutics, Salix Pharmaceuticals, and as a regional attorney at Pfizer. “But now I’m becoming increasingly of the opinion that there is an inherent tension between legal and compliance, and if [compliance] is subordinate to legal, it’s inevitable that an issue will rise up which literally speaks to this conflict of interest.”

For more on the issue of compliance, and how companies are bringing compliance personnel into the upper echelons of senior management, look for PharmExec’s feature on the subject in the January issue. Additionally, Ayers and many other pharma compliance executives and government regulators will be on hand for CBI’s 10^th Annual Pharmaceutical Compliance Congress, to be held at the Ritz-Carlton in Washington DC on January 29–30.