 that compliance professionals are faced with an ever-changing environment of state and federal regulatory requirements. Staying compliant requires more diligence and resourcefulness than ever before. But having the underlying knowledge remains paramount; it is extremely difficult to fully comply with something that is not properly understood. Successful compliance requires an in-depth understanding of both the big-picture goals of regulators and the practical nuances of applied best practices. Learning and knowledge-sharing are the vehicles to that understanding.

Today’s expanded vision of compliance learning and sharing includes exploration of important issues such as the safety and security of our drug supply chain, drug sample distribution and other marketing initiatives, transparency requirements, fraud and abuse, ever-changing state regulations, and much more. That’s why 2017 marks a significant milestone for The PDMA Alliance: our transition to a new brand identity.

In 1990, a small group of pharmaceutical executives responsible for compliance to the Prescription Drug Marketing Act of 1987 (PDMA) came together to discuss the relatively new PDMA and how it was impacting their work days. They shared ideas and networked on issues related to sample accountability. The group continued to meet annually and grew to become The PDMA Alliance, a not-for-profit organization. The PDMA Alliance was founded “by the industry, for the industry” as the voice of pharmaceutical, medical device and biotech compliance professionals.

Over the following 27 years, the Alliance has expanded its knowledge base well beyond the Prescription Drug Marketing Act of 1987, incorporating new content each year to reflect the challenges facing our members: OIG guidelines, corporate integrity agreements, Open Payments, aggregate spend, investigations, the Drug Supply Chain Security Act, 340B drug pricing program and more.

To complement this new knowledge, we recognized the need to modify our identity. Over the next few months, you will see our brand fully evolve from The PDMA Alliance into The Sharing Alliance. Our rationale for this is sound: We are well aware that the issues challenging pharmaceutical, medical device and biotech compliance professionals are both broad and deep. Most certainly, compliance with the PDMA remains an important industry concern, and we will continue to share our expertise in this area with our membership. But as pharma, biotech and device compliance needs have changed and multiplied, the Alliance has expanded in response. We haven’t lost touch with our roots and still consider ourselves to be the premier resource on PDMA compliance; instead, we’ve expanded to deliver even more to the compliance community.

Our organization is comprised of people like you: professionals at pharmaceutical, medical device and biotech companies who work in compliance, marketing, legal, sales ops and other job functions who are motivated to help address the health concerns of our nation while adhering to federal and state regulatory mandates. They attend our annual conference and become year-round members of our learning community. Some even volunteer to serve on our Board and work together to identify ways the Alliance can better serve its members.

The Alliance maintains good relationships with the US Food and Drug Administration (FDA), Centers for Medicare and Medicaid Services (CMS), the Office of Inspector General (OIG) and other agencies to continually understand and educate the industry on pharmaceutical, biotech and medical device compliance business, and security best practices. The Alliance Board is committed to the ongoing expansion of the not-for-profit Alliance by supporting members through dynamic pharmaceutical industry changes and challenges.

Our mission is clear: to improve the understanding of laws and regulations that most impact the compliance professionals that make up our membership; to help facilitate the communication and sharing of compliance best practices; and to continue the legacy of excellence the Alliance has held for more than 25 years.

This October, there is a real opportunity at the 2017 Sharing Conference to gain insights about the most important compliance issues that are surfacing from our changing culture. Together, compliance specialists will have the opportunity to rid themselves of obstacles that cloud the path to a clear vision.

Our program is chock full of learning opportunities, with more than 20 sessions over two and a half days. Attendees will hear from speakers representing the US Government, the biopharma industry, the medical device industry and the vendor community that supports the conference.

The Alliance continues to foster communications between industry and CMS. At the Sharing Conference, attendees will get the opportunity to have transparency reporting questions answered directly from CMS Open Payments representatives, led by Robin Usi, director of the Division of Data and Informatics (DDI). Questions for CMS can be sent in prior to the conference or during the Town Hall meeting itself. Previous attendees have told us that these Town Hall sessions are a great way to get clarification on specific requirements while providing a platform to alert CMS to specific challenges manufacturers face when compiling federal reports.

Over the past 25-plus years, the Alliance has been privileged to have members of FDA, CDER and OIG regularly present at the Sharing Conference. Plans for this year’s conference are ongoing; detailed announcements on speakers and topics will be posted to sharingalliance.org and sent via email notification. You can join our mailing list by using the Contact Us link on our website.

No compliance event offers as many learning opportunities in 2 ½ days as the Sharing Conference. This fall, we will be delivering more than twenty, hour-long workshops on diverse topics, including:

Successful compliance training strategies

Project management: doing business using lean principles

Techniques for easing system implementations

Ensuring quality and product safety in cold chain distribution

Compliance 101 for pharmaceutical & medical device professionals

Ensuring compliance in sample delivery processes

Data integrity: keeping up with HCPs on the move

Aligning US transparency initiatives with global requirements

Fraud and abuse of co-pay cards, coupons and vouchers

Successfully partnering with a contract sales organization

As always, the learning session agenda will also include our “Sharing” forums. Attendees value the chance to discuss any and all compliance-related subjects with conference colleagues in this interactive open forum setting.

Our conference agenda also includes eight “Speed Sessions” designed to provide attendees with a 15-minute introduction to important, emerging issues. Scheduled topics include:

UDI—medical device security, tracking and protection

Life After a Corporate Integrity Agreement (CIA)

As this article went to press, the Alliance was finalizing plans to add an exciting Special Guest Speaker to our agenda. This guest is likely to keep attendees on the edge of their seats with a story that is exciting, engaging and motivating. His headline-making experiences are sure to be a can’t-miss hour. Make sure you visit 

 regularly for this important announcement.

As you can see, 2017 is an eventful year for both the Sharing Alliance and the Sharing Conference, which means it’s also an eventful year for our Alliance members. We’ve expanded our content. We’ve sharpened our focus. We’ve rebranded to better identify what we offer. And we’ve gathered an impressive collection of speakers and presenters to deliver some very important information. If you haven’t already registered to attend the conference and become an Alliance member there’s still time. See you in October!

Deb Segura is executive director of The Sharing Alliance (formerly known as The PDMA Alliance; 

Articles

The Sharing Conference returns to Baltimore in 2017

Clearing the path by understanding the obstacles: The 2017 Sharing Conference

 the life sciences industry has expanded its capacity to treat patients addicted to pain killers by 91%. However, treatment center coverage remains uneven in the hardest-hit rural communities where emergency services may be limited, treatment options sparse, and more people endure chronic pain from working in labor-intensive occupations. If life sciences companies were equipped with such up-to-date patient data, they could more closely match the rapidly evolving needs of patient communities and promote treatment options to healthcare professionals (HCPs) serving these deficient areas.

Project Lazarus (www.projectlazarus.org) is an example where data empowered organizations to swiftly redirect efforts to help thousands of patients recover from the misuse of opioids in an underserved area. The community of Wilkes County, NC in the foothills of the Appalachian Mountains has fewer than 70,000 residents, but the third-highest prescription opioid overdose rate in the nation. Project Lazarus encourages cross-sector collaboration, promotes public and provider education, and focuses on increasing access to treatment. Purdue Pharma, schooled in the patient data, invested in the program and helped cut the overdose rate in Wilkes County by 72% over three years.

No single system can—nor should—maintain the universe of patient information as well as the patient’s relationships with doctors, specialists, current prescriptions, healthcare payer and plan. To get the most benefit from patient data, it must be made accessible in multiple systems. To do this, all data points must be ‘related’ to one another, which requires each patient to be assigned a unique identifier, but this process can become very complicated. Traditional approaches are not sufficient for today’s large quantities of multifaceted healthcare data.

Modern data management applications solve this problem by linking patient data across an organization’s IT landscape, which ensures data consistency among systems. This advanced technology relates all patient data so that when it changes, the change is reflected instantly across all systems. Unlike other types of data technology, MDM can also manage multiple data sources, structured and unstructured data, and inconsistently formatted data.

MDM also provides additional capabilities for data quality, data stewardship, survivorship rules, access rights and other data governance needs, and can centralize it all for consistency around the world. Queries aggregate data across multiple systems while cloud-based solutions capture data changes in real time to form a reliable, 360-degree view of patients. With this comprehensive view, life sciences companies can finely target their marketing, personalize care, and promote treatments where they are needed most.

One global pharmaceutical company has initiated a pilot program to more fully leverage patient data to build closer relationships with them and their caregivers. However, with numerous entry points and channels, the data is too easily fragmented and ungoverned. The company is turning to MDM to match, link, cleanse, validate and standardize patient information and to accurately relate patients with their HCPs, insurance companies and products with the ultimate goal of improving patient care.

MDM is especially beneficial for long-term care patients like the growing population of baby boomers, oncology patients and opioid addicts. High-touch specialists who treat these chronic conditions can dramatically improve their quality of care knowing key information about patients, such as their primary care physician and specialists, hospital preference, other prescriptions, payer plan, and approved products on the payer’s formulary. And drug companies that share patient data with prescribers can engage in a more collaborative relationship with doctors and help them adjust treatment accordingly.

Additionally, as more patients start using wearable or injectable devices, valuable real-world adherence data (i.e., time of day a dose is taken, dosage amount, frequency) can also be shared and inform treating physicians. This could have powerful implications for patients taking ongoing medications, such as those with Type II diabetes. Life sciences companies that can effectively manage and provide this type of master patient data to HCPs in combination with treatment information foster rich partnerships with doctors in the battle against disease.

Patient data saves lives

has a customer list. It remains a very basic, yet very challenging, part of how the pharma industry interacts with its primary customers, the healthcare providers: reliably identifying their location, credentials and affiliations (Fig. 1). For many years, the IT industry has addressed these needs (and those of other industries) with “master data management” (MDM) software. For life sciences companies, the game changed quickly to matching physician demographics with their prescribing behavior; another driver was the Prescription Drug Marketing Act (PDMA), which now requires tracking how many drug samples are delivered to a physician. In addition, corporate integrity agreements (CIAs) often specify which drugs can be sampled to which physicians.

Another driver—which the industry is still resolving—is the Physician Payments Sunshine Act, which led to the Open Payments system operated by CMS. The Sunshine Act (which, it’s worth noting, was a part of the Affordable Care Act that the current administration still wrestles with repealing) requires tying “transfers of value” (which could be a pizza delivered to a doctor’s office by a rep) to the specific physician, aggregating the spending across companies and interactions, and then making that data publicly available. From its high-drama first years of implementation (Pharmaceutical Commerce, July/Aug 2014, p. 14) to now, the annual Open Payments report has become a matter of routine, but there are significant changes going on, both in the US and abroad, over this type of transparency in pharma activity.

 Fig. 1. What affiliations a prescriber has affects the contractual terms of drug dispensing.

While these compliance requirements were evolving, so was the technology. MDM used to be looked on as basic plumbing for managing sales territories and keeping track of contact information of prescribers; now it is becoming the foundation of higher-level business intelligence and analytics, including the Big Data applications that have arisen from the large-scale communications and e-commerce like Amazon or Google. And it’s all moving to the cloud, although there is considerable debate about how best to take advantage of these technologies.

The one constant that can be discerned in both the business applications and the technology is speed of obtaining, verifying and deploying MDM data. “It’s amazing what’s happened in the past five years,” says Greg Ungemach, product specialist at MedPro Systems, one of the leading US providers of master data. “Clients were accustomed to annual or semi-annual updates of prescriber lists; now this information comes faster, from a broader set of sources, and is updated in days or even hours.” Some of this speedup is through retrieving digital data from repositories—a “machine to machine” connection, but Ungemach says that manual processes and stewardship are still a vital supplement to providing validated, reliable data.

“We track how quickly we can update a DCR [data change request] that might come in from a field rep visiting a doctor’s new location,” says Jim Cushman, VP and GM for Veeva OpenData, that company’s reference data service. “We can verify and update a record in less than five hours for 60% of DCRs, and 95% within 24 hours.” He goes on to note that in the past, the unreliability of master data often compelled users to block updates for days or weeks to allow data to be validated. “Overall data governance is better.”

Technologies are growing in number; applications are growing in number, but the vendors appear to be shrinking, especially on the data-gathering side. IMS Health (now QuintilesIMS), a longtime power in the reference data-gathering world, purchased Cegedim Relationship Management, owners of the OneKey global database in 2014; since then, it acquired Healthcare Data Solutions, another data provider, and two application-oriented firms, Privacy Analytics and Polaris Management Partners. LexisNexis, big in financial and insurance data, acquired Health Market Science in 2014. Veeva acquired AdvantageMS in 2013, and several overseas data houses. Most recently, PRA Health Sciences acquired Symphony Health Solutions—a pairing of a data provider (mostly of scrip and claims data, but also MDM reference data) and a contract research organization (CRO), just as Quintiles and IMS’ merger has linked the two.

These merged entities boast an ever-growing universe of healthcare provider (HCP) reference data: MedPro, 21 million records (primarily US); QuintilesIMS, 13 million; and Veeva, 20 million. LexisNexis claims seven billion name/address combinations (across its universe of personal and professional data). As these numbers indicate, the reference-data universe is tipping beyond HCPs and into patient databases—more about that later.

For fulfilling the traditional, basic role of an MDM—providing a sales rep with current contact information—there is a close tie-in between the MDM service and sales force automation tools, such as customer relationship management (CRM) solutions. “We got into this business because our CRM customers had problems with the data they were seeing, and blamed the Veeva CRM software,” says Cushman. Now, there can be a seamless integration between Veeva’s CRM products and its MDM reference data. Likewise, QuintilesIMS brought in both Cegedim’s CRM and its OneKey data with the acquisition; IMS Health had its own CRM platform, and has since announced new efforts in that arena. However, these and other CRM providers stress that clients have the ability to integrate other data sources of their choosing into the CRM systems.

These “other data sources” capabilities are a topic of bitter contention between Veeva and QuintilesIMS. In January, following what is said (on both sides) to be years of continually trying to resolve a data-access arrangement that would preserve proprietary QuintilesIMS data and methods, QuintilesIMS filed suit in New Jersey federal court (Case No. 2:17-cv-00177) claiming theft of trade secrets, false advertising, unfair trade practices and three other counts. Veeva then countersued, claiming antitrust violations and unfair competition.

Part of the underlying logic of QuintilesIMS’ position is the approach Veeva takes to how its reference data is updated. According to Cushman, when a Veeva client sends in a data change request (DCR), it goes through the Veeva validation process (which can include the intervention of more than 100 data stewards in the US, and a couple hundred more in offices overseas), and then becomes an updated record available to all Veeva clients. (There are contractual items involving how detailed this is; for example, the record might include an HCP’s communication channel preference, information that could be considered proprietary by the originating DCR, which would not be conveyed over to OpenData.) QuintilesIMS keeps client data contained for each client, asserting that competing pharma clients do not want to share fresh data with each other.

It is possible, however, for Veeva data and QuintilesIMS data to co-exist with the same client, by means of third-party agreements (TPAs) between the various parties. “We put up a firewall such that we can push into the client’s instance of another reference data set, but that data set can’t push out to our data,” says John Busalacchi, senior principal in QuintilesIMS Enterprise Information Management center of excellence. “The client decides which reference data to use as its core.”’

QuintilesIMS’ suit maintains that these TPA have been abused; for its part, Veeva says that it provides a migration path for a current user of QuintilesIMS data to shift to Veeva’s reference data. The litigation, according to the firms, is about to enter a due diligence phase; it could go on for years.

Coming at the data validation process from another direction, LexisNexis provides what it calls a master file Data Enhancement Service; a client’s existing reference data is digitally matched against LexisNexis’ master files, and a report reconciling the two is issued. Josh Schoeller, VP, healthcare markets for LexisNexis, says that any master file degrades quickly—“physicians’ affiliations change at a rate of 30% per year, and our verification tests have shown that we can typically raise the quality of a file by 20 percentage points. We can then benchmark the quality level of the existing database, and an MDM manager can calculate an ROI in terms of improved sales team accuracy.”

MedPro (which stresses its linkage to any MDM software) highlights its linkage with Concur, a popular resource for recording and tracking travel expenses and other field-rep activities; MedPro was declared “App Center Partner of the Year” in 2017 by that firm. (Veeva and other CRM players also interact with Concur.) “Typically, a rep will record a recent doctor’s office visit in Concur, and by hitting one button, that HCP’s location and licensing information will be automatically populated with the latest MedPro data,” says Ungemach.

Although location and certifications are often considered commoditized—undifferentiated parts of MDM reference data, in fact—the topic continues to cause worry for data managers. A notable irritant is the reporting for aggregate spending under the US’s Open Payments system, and the now-established transparency standards in the EU. In the US, agg spend reporting is fairly settled; when CMS published the 2016 data on June 30, there was barely notice taken in the popular press. (ProPublica, an investigative journalism organization that had been publishing a “Dollars for Docs” report even before Open Payments, did not update its reporting this year.)

For the record, the industry reported $8.18 billion being spent on physicians and healthcare organizations and related revenue transfers; it was up by a mere 1.1% from the $8.09 billion reported in 2015. (The 2015 figure was revised based on later analysis by CMS; the original figure was $7.49 billion.) Of that, $2.8 billion was spent on “general” payments (this would include most sales-rep expenditures), but that hardly budged from the $2.68 billion spent in 2015.

A key MDM element of agg spend reporting is the National Provider Identifier (NPI) number of physicians; but here’s where such reporting gets complicated: this year, the state of Ohio established a new rule for its so-called Terminal Distributor of Dangerous Drugs (TDDD) program, which is a licensing registration for who handles most types of prescription medicines (the definition of a “dangerous drug” is one that is only available by prescription). Now, not only is the physician responsible for receiving a drug required to be identified to the state, but also the specific location where the sample was dropped off. “Doctors maintain multiple offices, so now you need to correlate who received the sample with the location of the physician,” notes MedPro’s Ungemach. “It’s essentially temporarily shut down sampling in that state until pharma companies’ databases have this information collated.”

Ohio’s rationale for changing the TDDD rules is to get a better handle on the sampling of controlled substances; however, the rule goes well beyond controlled substances. And while sampling is required to be documented nationally under the Prescription Drug Marketing Act, some states make the sample part of what gets reported as an Open Payments-type transfer of value.

The Open Payments requirements demonstrate both how many parts of a pharma company need to track interactions with HCPS (Fig. 2) and what companies have been doing to address the need (Fig. 3). QuintilesIMS, which published a “US Trends in Aggregate Spending” survey last October, concluded that “manufacturers are not closing the book on their transparency initiatives; rather, they are just beginning the second chapter as they identify opportunities to achieve a more efficient and effective compliance operation.”

NPI numbers are just the beginning of the physician categorizations that today’s MDM systems are achieving. There are also DEA registration numbers (which used to be the default numerical ID before NPI became widely established); state medical licenses (a significant number of physicians operate in more than one state); certifications by medical specialty (which, under PDMA rules dictates what drugs can be sampled to which specialties). LexisNexis touts its sourcing of data from a consortium of 70 payers (insurers), which generates 1.6 billion medical claims annually, and whose data is used by CMS itself in tracking public insurance payments. “A good part of this work is for the benefit of healthcare providers,” says Schoeller, “but we have the opportunity to leverage this data to the pharma industry.”

The lion’s share of attention is currently focused on affiliations—which health systems prescribers belong to, and which pharmacy benefit managers and health plans have agreements with those systems. With the shift to market access teams to address prescription choices at institutional as well as individual prescriber levels, these connections become vital.

According to QuintilesIMS’ Busalacchi, affiliation data (which can also tie into related topics like formulary decisions and other factors) can best be addressed by taking an enterprise information management (EIM) perspective on MDM systems. QuintilesIMS calls this the “orchestrated customer experience,” and it could include any relevant MDM data, combined with the claims data that QuintilesIMS has been providing the industry for years, and with affiliation details as well as both structured and unstructured data (i.e., data that has not been organized into an integrated fashion). The orchestrated customer experience is branded as IMS One, but IMS One has significant technology components to it.

A key element, says Busalacchi, is a close partnership QuintilesIMS has with Reltio, a San Francisco, CA company that deploys Big Data technology to link and then visualize diverse massive data sets. According to Ajay Khanna, VP of marketing at the firm (and a former Veeva employee), one component of Reltio’s offering is a proprietary type of graphing technology (“graphing” is a term of art in organizing large data sets).

“Our graphing technology enables a user of the data to quickly pivot from, say, a view of a prescriber and that person’s affiliations, to one of the affiliations and all the other prescribers connected to it,” he says. “Additionally, a new data set or dimension can be added and the system quickly adjusts.” With conventional relational databases—or traditional MDM technology—such switching could only be carried out by reprogramming the MDM software, taking time and effort and making the maintenance of the reference data heavily burdensome.

QuintilesIMS is a value-added reseller of Reltio technology, but IMS One includes other features that QuintilesIMS is bringing together to make IMS One a “platform” for EIM, notes Busalacchi. Specific elements include Amazon Web Services such as S3, and the IMS One platform is being designed to be open to a variety of analytics services and other data-storage systems (QuintilesIMS had earlier announced relationships with Cloudera, a data-storage technology company, and with Salesforce.com, whose Force.com platform enables applications to be built quickly).

Veeva—ever ready to go at QuintilesIMS it seems—proposes a different approach. “You don’t need to bring complex analytics tools into MDM to get useful insights from it,” says Veeva’s Cushman. “You’re not going to train hundreds of field reps in data science to get a multidimensional view of their clients.” Veeva offers what is called “portlet” technology that enables data to be viewed from the MDM database, rather than generating integrations to the various other software applications. Having said that, however, Veeva’s OpenData system is accessible to those analytics systems should clients desire it. Veeva’s overall data platform is branded as Veeva Network, and Network enables easy tie-ins to other Veeva products, such as its Vault application for storing and tracking (among other things) promotional materials.

Both LexisNexis and MedPro have partnerships with Reltio, and Reltio’s Khanna says that the company aspires to be an open platform accessible to the growing array of Big Data resources now on the market.

The ease with which large data sets can now be handled with cloud-based systems that offer low expense and high availability opens up another area of opportunity for the pharma industry: patient data, and dealing with patients directly.

LexisNexis’ Schoeller makes a point seldom recognized by pharma marketers: with opt-in systems, the pharma industry has a direct connection to patients; the challenge has been, what to do with it? “There hasn’t been a lot of utility to get more out of these registries than name and address standardization, but the opportunity is present to match identity data with lifestyle contexts, to get better insights into patient behaviors,” he says.

A way to address patient outcomes (without identifying specific patients) is the Systems of Care data service the company now offers, which is organized around the “social health” of patients. The service has been started initially to provide health systems with better characterization of their extended services (so that, for example, helpful lab tests can be targeted for certain therapy areas). Schoeller says that the methodology is going to be extended to patient populations during the coming year, as a potential boost for adherence programs

) notes that patient data organized in an MDM system is providing benefits to fighting the opioid crisis. And he (and others) point to the coming of wearable devices for medical monitoring, and the potential to interact with patients directly based on readouts from those devices (whether this information will flow to pharma manufacturers remains to be seen).

All of this, of course, threads the needle carefully with regard to patient privacy and HIPAA requirements. Reltio’s Khanna notes that the drive toward pay-for-performance agreements in healthcare, along with value-based contracting for pharma sales directly, is opening up channels of communication and information-sharing among payers, providers, patients and the pharma industry. It’s worth noting that Amazon Web Services, as part of its offerings to participants in healthcare, has already created resources for healthcare organizations to comply with HIPAA standards as they convey their data to cloud-based systems.

Looking for the equivalent of the US’s Open Payments system—one public repository where payments to individual HCPs is revealed and updated annually—is an eye-watering exercise in Europe. It’s not necessarily that there’s less intense public interest in the topic, but that the multinational regulatory practices across the continent allow for differing procedures, and individual privacy rights are more strongly guarded. Legislators and public interest groups who propelled the transparency initiatives had to engage in one negotiation with industry, and another with the professional organizations of HCPs, and the standards practices of those organizations.

All members of EFPIA, the European Federation of Pharmaceutical Industries and Associations (and the member companies in these associations) have agreed to provide annual reports on transfers of value to HCPs, but EFPIA does not attempt to aggregate all companies’ reports. Some countries, notably the UK, France and several other nations, have a central repository; in other cases, companies operating in the various nations report activity in each nation. EFPIA comprises 33 nations, five more than the EU.

Then there are the standards as to what’s reported. Again, there are variations, but as far as EFPIA is concerned, the key reporting on an individual basis is the funding of meetings and travel to them, speaking engagements and consulting arrangements. R&D expenditures are reported in the aggregate for each organization (other EU rules on clinical trials require identifying clinical trial investigators, but the trial funding and the investigator are apparently not combined). “Hospitality” expenditures on meals and drinks are generally not reported (considered “a disproportionate administrative burden” by EFPIA), but this varies by nation, too.

All that being said, data is beginning to come forward; EFPIA had a June 30 deadline for member companies to file reports. In the UK, the Disclosure UK program is in its second year: in June, it reported that members of the Assn. of British Pharmaceutical Industries reported a total of £454.5 million ($586.3 million) spent with HCPs and healthcare organizations—a 25% increase from 2015 (£363 million). The increase is tied to more R&D spending, said to represent 74% of total expenditures. The number of HCPs allowing individual data to be published also increased to 65% (the increased participation is not directly tied to the increased announced expenditure, which is an aggregate figure).

When it comes to individual company reports, it appears hard to beat Novartis, which has published transparency data (mostly tied to organizations, not individuals) across 38 nations. The reports are listed on one 

, but in each country’s language and currency.

The pharma industry has a growing number of dependencies on reliable master data

MDM’s growing role in running healthcare businesses

is deluged with data. However, because data is seldom standardized, companies cannot fully tap its potential to substantially reduce the failure rates in drug development. [1] By consciously streamlining and unifying data, drugmakers can improve efficiency throughout the four stages of clinical development—from design and start-up through execution and submission.

As a case in point, during the clinical development design phase, companies can integrate data from multiple sources to build a clear patient profile. Social media, patient focus groups and disease advocacy groups are all excellent sources of potentially valuable data. For endpoint selection, pertinent data sources may include similar trials, basic research, regulatory filings and payer data. Dose selection can also be better met with data from preclinical studies, population data and other sources that would allow successful simulations and predictions of dose response curves.

In our experience, it is important for companies to leverage both their internal, as well external, data. This is something that we routinely do when we optimize protocols—both from a design, as well as an execution perspective. To enable the above, we have created a metadata repository (MDR), which applies standardization and traceability from protocol generation (e.g., endpoints, visit structure), through data collection, mapping, statistical analysis and reporting, on through preparation of the clinical study report (CSR) (see graphic). Conventionally, the various individuals and teams responsible for these activities start from scratch to write their own sections of protocol, develop the electronic database and program the statistical analysis. This process can be cumbersome and has the potential to cause issues down the line. Our MDR approach allows us to standardize and expedite these tasks through automation, ensuring consistency in language and data collection.

An example of how metadata standardization works (and an illustration of data complexity overall) can be seen in this example: the collection of gender information. Every clinical study collects this information in the demography domain. The clinical data behind this concept would be “male,” “female,” “unknown,” and “undifferentiated.” This gender information for a given subject will be collected in different places by different people and systems for a given study (e.g. clinical data base, central laboratory, randomization system, specialty lab, clinical management system, etc.). The metadata for this item should follow the established industry Clinical Data Interchange Standards Consortium (CDISC) Standards, with “sex” as an item name and the values “M” and “F” for male and female. However, in many cases even in this very simple example we see different data sources using metadata such as “sex,” “gender” and actual clinical data such as “male, female,” ”M, F,” ”man, woman,” “0, 1,” “1, 2” or other variations. When these different data sources are then being put together, an enormous amount of mapping through programming needs to be put in place to allow to combine data. The complexity level increases for other examples, such as laboratory data with different test codes.

Research organizations around the globe are increasingly advocating and implementing data standardization. In 2012, the collaborative non-profit organization, TransCelerate Biopharma, introduced a Common Protocol Template (CPT) to provide a foundation for electronic protocols. [2] In addition, the US Food and Drug Administration (FDA) and the National Institutes of Health (NIH) last month announced availability of their own joint template, including sample language and instructions, to help researchers prepare Phase II and III clinical trial protocol. [3] Many fresh efforts to harness disparate data sets are likely to influence the conduct and design of clinical research going forward. The 21st Century Cures Act, passed by Congress several months ago, is a case in point. It may enable drugmakers requesting regulatory review of experimental treatments to bypass full clinical trials and instead submit “data summaries” and “real-world evidence,” such as observational studies and insurance claims data. [4] For its part, the Patient-Centered Outcomes Research Institute (PCORI) seeks to enhance engagement of clinical research stakeholders, including patients, caregivers and prescribing physicians. As PCORI and other groups fund investigations of highly complex issues, such as the best means of managing symptoms of end-stage illness across disease categories, standardization of data and methods for analyzing it will be key. [5]

Around the globe, it's clear that data-oriented research efforts will soon afford drugmakers access to data truly meaningful for clinical development. Some of the most visible include the United Kingdom's Clinical Practice Research Datalink (CPRD), the European Commission's eHealth Interoperability Framework, and the Structured Data Capture (SDC) Initiative. Guidance issued by FDA [6] and the European Medicines Agency (EMA) [7] also make plain that electronic health records (EHRs) will have a growing impact on healthcare and research.

Companies can harness standardized data during the start-up phase of development. Examples include site enrollment and performance on previous trials, epidemiological data, etc. Critical to unlocking insights from these standardized data sources is expertise with data storage architecture, ability to search across different data structures, data visualization capabilities, predictive analytics and more.

In the clinical development execution phase, standardized operational data can help companies save time and money by making it easier to determine whether the data being gathered from patients are in line with trial objectives. As a best practice, organizations should leverage a statistical monitoring approach to help data withstand regulatory scrutiny. Visual presentations of scientific data should be geared towards people with specific responsibilities and skills, such as data management, clinical, medical and statistical team members.

Beyond data processing, technological advances in data capture are also changing what's possible in the execution of clinical trials. Wearable devices equipped with sensors are swiftly becoming viable means for collecting clinical data from human patients in a real-world setting. Eventually, data captured via wearable sensor technology might be taken directly from a person's electronic health record and into databases established for hybrid studies and/or site-less clinical trials.

Data standardization is already making a big impact on the final steps of clinical drug development—analysis and submission—and its importance will only increase. Specific data formats are now widely used, including Clinical Data Acquisition Standards Harmonization (CDASH), for data collection standards, the Study Data Tabulation Model (SDTM), for submission of clinical and non-clinical data to FDA. The Analysis Data Model (ADaM), an increasingly popular description of dataset and metadata standards, is guiding the creation of powerful, flexible structures for generating, analyzing and replicating clinical data. CDASH, SDTM and ADaM are championed by the CDISC, an international consortium well-regarded for its work to “let data speak the same language.” In addition, genomics and proteomics technologies dependent on massive data sets are not only helping drugmakers discover fresh targets, but also increasing their ability to predict and identify specific subgroups of patients likely to respond to treatment.

In May, FDA approved Keytruda (pembrolizumab) for patients that screen positive for a particular tumor biomarker. [8] The drug was approved for “microsatellite instability-high” or “mismatch repair-deficient” solid tumors, based on a study involving just 149 patients. Ninety had colorectal cancer, while the remaining 59 had one of 14 other tumor types. This is the first time a cancer treatment not linked to a tumor's original location in a particular tissue type has been approved.

Keytruda's approval, in connection with the drug's mode of action (influencing the immune system), rather than a specific tumor type, is a prime example of the power of strategic data standardization. The drug's developer was able to find individuals across a host of cohorts with a specific molecular identifier who would respond to this compound.

Gathering and organizing data for submission to FDA or other regulators is often considered a daunting task. Companies can, however, simplify the process by defining the data needed for submission during trial design. With this, protocol would automatically drive the database setup. Findings would be collected and analyzed in consistent ways and results

would flow more smoothly into the clinical study report.

The tremendous heterogeneity of healthcare information systems remains a key difficulty. It's a challenge with deep roots that pre-date the digital era: as just one example, there may be as many as 50 descriptions for myocardial infarction. Yet recent years have also seen genuine progress towards data standardization.

Companies should consider leveraging an outsourced partner early on to assist with gathering, storing and analyzing data. Many vital decisions made at the onset of trial design determine how each successive step of the development journey proceeds. Getting it right from the start can help organizations save time, mitigate risk and improve the overall clinical development process.

Biotechnology Industry Organization study, February 2011

www.transceleratebiopharmainc.com/common-protocol-template-now-available/

Marks, P. (2017). FDA and NIH Release Final Template for Clinical Trial Protocols. FDA Voice, May 2, 2017. (

https://blogs.fda.gov/fdavoice/index.php/2017/05/fda-and-nih-release-final-template-for-clinical-trial-protocols/

114th Congress, Public Law 255, Act: To accelerate the discovery, development, and delivery of 21st century cures, and for other purposes. US Government Publishing Office. December 13, 2016. 

Patient-Centered Outcomes Research Institute (

Use of Electronic Health Record Data in Clinical Investigations: Guidance for Industry, Draft Guidance. U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH), May 2016. 

www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM501068.pdf

European Medicines Agency, News and press releases (2017). Use of big data to improve human and animal health: Task force to establish roadmap and recommendations for use of big data in assessment of medicines. March 23, 2017. 

www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2017/03/news_detail_002718.jsp&mid=WC0b01ac058004d5c1

Martins, I. (2017). FDA Approves Merck’s Keytruda for Colorectal, Other Solid Cancers with Specific Genetic Feature. Colon Cancer News Today. May 25, 2017. 

https://coloncancernewstoday.com/2017/05/25/colorectal-cancer-patientsspecific-genetic-features-win-fda-approval-keytruda-access/

Sy Pretorius, MD, serves as senior vice president and chief scientific officer at Parexel, where Martin Roessner, MS, is vice president, global biostatistics; Michelle Hoiseth serves as vice president, Parexel Access; and Michael Goedde is vice president, clinical data management and database programming.

Global efforts to collect clinical data in a more standardized form will lead to more research innovation

The power of strategic data standardization

 logistics field, as 2017 begins to wind down, continues to expand and mutate as new technological and regulatory concerns come into play. While large parts of biopharma industry management assume that cold chain logistics is a routine activity (and one whose cost should continually decline), knowledgeable managers know that it is a critical part of successfully distributing the industry’s products—and ultimately the financial success of their undertakings.

Perhaps the most prominent new trend is the early success of some cellular therapy products, notably Novartis’ FDA review-committee approval of its CTL019 (tisagenlecleucel) therapy for a type of lymphoma. It is the first so-called CAR-T cell therapy, which depends on extracting T cells from a patient, reworking the cells’ genetics and then re-infusing to the same patient. CAR-T cell therapy is all the rage in clinical research circles; many more products are in the pipeline. If these therapies prove out commercially, they will translate into a demand not just for cold-chain logistics to patients, but also from patients.

That round-trip logistics activity is very similar to what goes on in a clinical trial: Investigational drugs go out, patient tissue, blood or other biomaterials go back. The clinical trial logistics component of overall cold-chain activity is thriving, drawing some of the major multinational logistics providers into what has heretofore been a focus of specialized courier services for the most part. The competition is intensifying.

A significant part of this work involves sub-zero (°C) shipping or even cryogenics: whereas the large majority of most pharma cold-chain activity has been to prevent sub-zero temperatures, now there are supply chains restricted to those temperatures.

Meanwhile, routine delivery of temperature-sensitive pharma products streams along, with new technologies appearing in packaging materials, phase-change materials (PCMs) and other sources of cold, and the containers for bulk shipments. The industry is getting more comfortable with reusable containers (setting up a reverse logistics process for the empties once a delivery has been made); ocean-going containers are being tailored more closely to life sciences needs; and more active (powered) container designs are appearing.

On the regulatory front, the dominant trend is the rising importance of good distribution practices (GDPs) for CRT shipping—in other words, nearly everything except cold chain shipments. This is proving to be a boost for the use of thermal blanketing (along with, or instead of, an insulated container) to make deliveries. GDPs have already wrought considerable changes in Europe, and the industry practices are gradually taking hold in the US and the rest of the world.

The CEIV Pharma (Center of Excellence for Independent Validators in Pharmaceutical Logistics) program, promulgated by the International Air Transport Assn., is becoming more widely accepted in the pharma logistics community. Although it originated with the airfreight world, it is being applied to warehouses, storage facilities and ground transportation services.

GDPs are also driving more sophisticated use of electronic monitoring and reporting equipment, ranging from throwaway sensors to elaborate global communications networks to track shipments by geography and by environmental conditions. Logistics providers are now capable of providing near-real-time monitoring of shipments, from the warehouse to the loading docks of pharmacies and hospitals.

at double the rate of non-cold chain" alignment="left"/>

All pharmaceutical products, as well as blood, other tissue-derived materials (which are usually regulated in the US as “medical devices”) and clinical trial materials used in drug trials, require close supervision when being transported from place of origin to place of use. Most products can be shipped at what is considered “room temperature;” the approved “label” (a detailed description of how the product is to be dispensed, along with side effects and other data) specifies the temperature range within which the product is safely stored and transported. To varying degrees around the world, regulators inspect storage facilities and review documentation of shipments to ensure that products remain safe and effective.

From roughly the 1990s to today, the regulatory framework around the pharma cold chain has become vastly more detailed; at the same time, the entry of biologically derived products has come to dominate much of the new drug development around the world, and almost by definition, biotech products require cold chain handling. The major pharma companies themselves have internal staffs of packaging and logistics engineers that work out acceptable devices and practices to ensure safe delivery. At the same time, a continually growing number of vendors, in transportation packaging, freight forwarding and transportation, and electronic monitoring of both a package’s internal conditions, and the processes followed by carriers, has arisen to meet the industry’s needs.

 analyzes the biopharma cold chain industry annually, and publishes its findings in its 

. The analysis is based on a large number of government, industry and private-company data and forecasts, both of volumes and costs. This analysis is supplemented with direct contact with many of the leading pharma companies and logistics providers. The analysis is refined as more data become available from year to year (so, to a certain degree, it is not valid to measure the forecasts in an earlier edition of the 

 with later editions.) On the other hand, our analysis, confirmed by six years of publishing the 

, has been validated by numerous consumers of the publication and its data.

, as in the previous editions, is premised primarily on two things: a methodical review of the labels of most common pharmaceutical and biotech products to calculate how much of the overall pharma supply chain is dedicated to cold chain practices; and an analysis of as much data as can be collected on the costs of pharmaceutical logistics in the US and globally. A third element is an evaluation of the pharmaceutical “pipeline”—the pace at which drugs under development will come on the market, and how the market will grow for those and for existing commercial products. The forecast time frame is five years (2016–2020).

Our updated forecast for cold-chain logistics spending in 2017 is that it will be more than $13 billion worldwide, in an $80 billion overall pharma logistics market, of which $9 billion will be transportation and $4 billion will be specialized tertiary packaging and instrumentation, such as insulated boxes, blankets, phase-change materials, active-temperature-control shipping containers, and various temperature sensors and recorders. By 2021, cold-chain biopharma logistics spending will expand to more than $16 billion (Fig. 3).

The bulk of this spending is on refrigerated (2–8 °C) products. The amount of frozen and cryogenic products is small by comparison. There is a trend toward more spending on devices and system for controlled room temperature (CRT) shipping, but to date, most of this involves more careful monitoring of shipping conditions, and greater use of temperature-controlled transport vehicles, and not necessarily extensive use of insulation or other environmental controls. With the expansion of cord-blood stem cell products, and other cellular therapies, there is also a trend to more cryogenics, below -150°C conditions maintained typically with liquid nitrogen.

The overall $80 billion biopharma logistics market can be further broken down by what is spent for transportation, and what is spent for packaging and instrumentation. For 2017, the breakout for cold-chain and non-cold-chain transport and packaging is shown in Fig. 2.

Finally, there is an analysis of logistics by mode—air, truck and ocean shipping. Most intercontinental shipping of cold chain products is by air. “Parcel” is generally regarded as packages smaller than pallets, and shipped internationally by air. Domestic parcel delivery is a combination of air and truck transport (Fig. 3).

Predictions of pharmaceutical shipments are one measure of the market growth; another is the warehousing, storage and transfer capacity going into place at third-party logistics (3PL) providers, air carriers and the depots of clinical trial materials providers. From a logistics industry perspective, the volumes of life sciences products are relatively insignificant, compared to minerals, automotive parts, foodstuffs and other high-volume industries; yet because life sciences can usually command premium-level service, it draws the attention of global players. And while it’s possible to use most temperature-controlled perishables space in the logistics industry for life sciences products, providers are increasingly building dedicated spaces for those products alone.

Near the end of last year, FedEx Supply Chain (formerly Genco) added 1.1 million sq. ft. in Memphis, TN and another 400,000 sq. ft. in Toronto, primarily for healthcare products (only an unspecified portion is refrigerated). The company can provide kitting and relabeling from the facilities, as well as basic logistics services.

Over the summer, Life Science Logistics brought on an additional 132,000 sq. ft. of capacity at its Indianapolis, IN facility, which has quintupled in size over the past two years. About 12% of the new capacity is given over to refrigerated product. LSL has four locations in the US. Its neighbor in Indianapolis, MD Logistics, also brought on more cold-chain capacity at its 173,000-sq.ft. facility; it also operates in Reno, NV.

UPS Healthcare Logistics, which operates more than 60 facilities for healthcare products worldwide, built a second facility near Bogotá, Colombia in the past year, adding 76,000 sq. ft. there, and bringing its global footprint to more than seven million sq. ft. The company also expanded its Express Critical delivery service, which has been in place in the US, to Europe.

Arch-rival DHL Global Forwarding opened a new Life Sciences Center of Excellence in Ireland, the 43rd country with such a facility (some countries have multiple Centers). The 40,000-sq. ft. facility is close to Dublin Airport, and features room-temperature, refrigerated and frozen dedicated capacity, along with repackaging services.

 also evaluates logistics spending trends in the clinical trials market. There are both pallet and parcel shipments of clinical trial materials, but no good way to characterize their respective volumes. A factor that is somewhat outside the scope of the 

 is return logistics that occur during clinical trials—the delivery of, for example, blood or tissue samples from a trial. Our analysis is based primarily on the trend in trial startups, enrollments and locations, along with estimates based on how much of a trial’s budget is dedicated to logistics issues (Fig. 4).

Clinical trial logistics involves shipment of products to be used in trials to study sites which may be dispersed around the globe, as well as shipment of medical samples to centralized analytical laboratories. This year, we are updating our estimate for the market size to about $3.2 billion in 2017, due to continued growth in the number and enrollment of trials, as well as pharma R&D. Based on estimates of trail volume, location and industry R&D spending overall, our forecast now is for a continued expansion of clinical trials logistics at a rate of about 2% per year, to about $3.4 billion by 2021.

In the clinical arena, the two market leaders are World Courier (now a unit of AmerisourceBergen) and Marken (now a unit of UPS). Both have been expanding capacity and technical offerings to the clinical market; last year, World Courier announced the Cocoon, a passive, pallet-size container to handle larger volumes of shipments in one container. World Courier is also stepping into handling commercial (as opposed to clinical) deliveries; a pilot program set up in Australia is being expanded to more of its network.

For its part, Marken moved into a new HQ in Research Triangle Park, NC this summer, noting that the company’s global staffing had expanded 40% over the past three years. The company also opened a Patient Communications Center in Philadelphia, intended to serve “the logistics needs of patients who participate in home-based clinical trials,” according to the company. Most freight forwarders or carriers have 24-hour control towers for their logistics partners, but a provider like Marken extending the service to clinical trial patients represents a deeper integration of logistics and life sciences.

There is a bewildering array of regulations and industry standards in biopharma cold chain transportation; in addition, nearly every nation of any significant size has a Ministry of Health (or equivalent) that publishes its own regulations. The most central regulatory framework, globally, is the Good Distribution Practices issued by the European Union. Many shipping processes within the EU are already influenced by this regulation, and many countries around the world are adopting versions of it. GDP standards are vitally important for cross-border shipments, because customs and health inspectors are charged with ensuring compliance. Within many countries, however, inspection and compliance with GDP standards are less strict; one factor justifying this is that the shipments can be delivered fairly expeditiously to local destinations once they have cleared customs (there are many exceptions to this, of course.) The 

 reviews GDP standards and other relevant guidance.

CEIV Pharma program of IATA entails audits and reviews of logistics practices, training and facilities, carried out by independent auditors. Compliance with IATA Temperature Control Regulations (TCR), EU GDPs and relevant standards of the US Pharmacopeia, among others, is part of the process. According to IATA literature, some 170 entities have already obtained the CEIV Pharma certification, mostly in the developing world, although the Brussels International Airport and France’s Charles de Gaulle airport have also won certification.

Kuehne + Nagel announced in January that it had obtained CEIV Pharma certification for all 86 airfreight facilities around the world that are part of its KN PharmaChain network. DHL Global Forwarding had seven of its 11 US facilities, plus Bogotá, Colombia, CEIV Pharma-certified as of last spring, and is rolling the program out to more of its global facilities. Delta Cargo obtained CEIV certification earlier this year, saying that it is the first US global passenger carrier to receive this certification.

American Airlines is in the process of obtaining certification for its Philadelphia, PA pharma hub; the company also announced widebody aircraft transit between Puerto Rico and that Philadelphia center, mentioning its pharma logistics specifically as one of the motivations for the expansion. (AA also serves that route with narrow-body aircraft.) Further enhancing its Philadelphia hub, AA opened an expanded life sciences storage facility at London’s Heathrow Airport.

IATA’s goals are ambitious; although its main business is airfreight, it is promoting CEIV Pharma for other supply chain entities, including warehouses and ground transportation.

Although pharma logistics is a relatively minor part of the overall logistics industry, it is generally a premium service that justifies higher prices. This, combined with the competitive pressure from service providers and carriers, has led to significant investment by the leading global firms, as well as expanded services from regional 3PLs and others. Several of the major global air cargo carriers have networks of cold chain “stations” around the globe to process healthcare products specifically. Innovative tracking systems have been developed, both by the logistics providers themselves, as well as by third parties, to monitor shipments, in real time in some cases. Logistics providers and freight forwarders have also set up “control towers” where dedicated staff monitor shipments en route, and can intervene to ensure safe delivery.

Packaging, instrumentation, specialized markets

Like the logistics providers, companies specializing in transportation packaging and instrumentation have brought forth a continuing stream of innovations and new capabilities. There is a clear delineation between “active” containers (those that have internal refrigeration systems, generally powered by batteries), and “passive” containers (those containing a set amount of chilled material to provide cooling). In theory, with proper management of power sources, an active container can keep a cold chain product safe indefinitely—providing insurance that a shipment can be safely delivered even when flight or trucking schedules are upset. Meanwhile, suppliers of passive systems have continually evolved better types of insulation, and innovations in how temperature is maintained within the container, all to extend the duration that the container can sustain. Most active containers need to be returned for reuse (they are expensive as a capital asset, and are generally leased); most passive containers are less expensive and generally single-use (there are numerous exceptions). The overall cost of a shipment is a balance between the cost of the container, the cost to ship the container itself (factoring in how much weight and how much product volume can be contained), and return-logistics or disposal costs.

In the controlled room-temperature arena, Q Sales, one of the leaders in this space, reports that its thermal blanketing products are being boosted by the move toward GDP regulation of CRT shipments; blanketing represents a lower-cost option for shippers than dedicated containers with insulation panels and gel pack refrigerants. Ensuring the temperature control of the shipment necessitates matching the product specs with the temperature environment of the shipment; this is one of the reasons that Q Sales forged a partnership with a company, Riskpulse, that analyzes weather conditions of shipping lanes and performs weather forecasts.

DuPont, makers of the well-known Tyvek sheeting that has temperature- and vapor-control properties, announced a “breathable,” “third-generation” blanketing product early this year. The technology provides temperature protection while minimizing the occurrence of condensation accumulation.

On the instrumentation front, technologies range from simple indicators based on chemical or physical processes and giving a “yes/no” result, to data loggers, to multi-capability environmental monitors for temperature, humidity, vibration and other factors, combined with satellite or cellular communications. These advanced systems integrate with online communications networks, enabling global tracking in near real time.

A comprehensive directory of carriers, logistics service providers, packaging and instrumentation vendors, and consulting organizations follows.

“Cold chain” now means cryogenic and ambient shipping, as well as the traditional 2–8° range

2017 Cold Chain Outlook

Click to view or download a PDF of the Directory.

Cold Chain 2017 Directory

If the position of the Commission on Combating Drug Addiction and the Opioid Crisis is to be believed, the US is in the midst of a national public health emergency on par with a natural disaster or terrorist attack, and immediate action is called for. Yet, this interim report was prepared in the midst of the rancorous debate over repealing Obamacare—regarded by its opponents as an unnecessary intrusion of the federal government into healthcare—and so the result is an odd combination of a call to action combined with “listening sessions” and public hearings, and a goal of issuing a final report Oct. 1. (The Commission missed the original deadline for submitting an interim report, as specified by President Trump’s March 29 executive order, by a month already.) In August, President Trump acknowledged that the crisis is emergency-level, but as of press time had not directed any new federal effort.

Some of the delay might be the cognitive dissonance between the actions at the federal level called for while Congress has been debating many ways to reduce federal healthcare support. Among other items, the Commission calls for:

Expanding the availability of Medicaid funds for mental health programs (which would include substance abuse disorders [SUDs])

Mandating additional physician training, by HHS, for physicians involved in opioid prescribing

Funding more medication-assisted treatment (MAT), which would be a boon for anti-abuse drugs such as buprenorphine; there’s also mention of having NIH “to begin to immediately work with the pharmaceutical industry” to develop non-opioid pain relievers

Federal funding to expand data-sharing across state lines in prescription drug monitoring programs (PDMPs), currently in use in 49 states.

All of these call for increased federal funding and agency involvement in healthcare industry practices; some of them could be implemented immediately, raising the question of what is the holdup?

The Drug Enforcement Administration (DEA) shows up in the interim report as the enforcer of additional education verification for prescribers, and as one of the agencies to combat the illegal importation of fentanyl, heroin and other opioid-based drugs. In the past year, besides the everyday interdiction that DEA (and other agencies) perform, DEA and the Dept. of Justice have been levying heavy fines against both drug distributors (each of the Big three has been hit, most notably McKesson’s record $150-million settlement in January) and manufacturers. The manufacturer targeting is a new development: now, manufacturers are being called on to maintain “suspicious order monitoring” (SOM) systems, just like distributors. In early July, Mallinckrodt settled with DoJ on a $35-million civil fine; Mallinckrodt is one of the largest manufacturers of generic oxycodone. The DoJ statement noted that:

[T]he government learned that manufacturers of pharmaceuticals offer discounts, known as ‘chargebacks,’ based on sales to certain downstream customers. Distributors provide information on the downstream customer purchases to obtain the discount. The groundbreaking nature of the settlement involves requiring a manufacturer to utilize chargeback and similar data to monitor and report to DEA suspicious sales of its oxycodone at the next level in the supply chain, typically sales from distributors to independent and small chain pharmacy and pain clinic customers.

It has not been the case, historically, that manufacturer chargeback management is a resource for preventing drug abuse; that might now be changing.

At first glance, the settlements with DoJ are surprising, given that a law, the Ensuring Patient Access and Effective Drug Enforcement Act, was passed in early 2016 specifically to create coordination between DEA and drug wholesalers and manufacturers over SOM. An interagency report to Congress was to have been developed by last April on how the involved parties could work together (as opposed to DEA simply shutting down warehouses of legitimate, registered businesses). Also, the members of the Healthcare Distribution Alliance (which lobbied energetically for the law) “await DEA’s guidance on suspicious order monitoring, which will go a long way to provide the additional clarity we seek on how we can be a productive and cooperative partner in the fight against prescription drug abuse,” according to John Parker, SVP, communications, at HDA.

Most of the recent settlements between industry and DoJ involve situations from the mid-2000s to the early 2010s—before the law was passed. Nevertheless, the settlements are bound to keep manufacturers and distributors on edge—as maybe they should be.

SOM, in theory, should not be profoundly difficult to implement (and to be sure, most major manufacturers and distributors have an SOM system in place—DEA, however, cites companies ignoring the output of their own SOM systems in some cases). The companies are supposed to use statistical techniques to watch for unusually high levels of opioid transactions, and question the legitimacy of those orders. Sumeet Singh, president of Five Rivers RX (King of Prussia, PA) says that his company offers a relatively low-cost statistical package suitable for small distributors to address DEA inspections, as well as consulting for overall DEA compliance. The company, which recently joined the Healthcare Distribution Alliance, has a primary business in assisting distributors in meeting the Verified-Accredited Wholesale Distributor (VAWD) accreditation program of the National Assn. of Boards of Pharmacy.

DEA was also in the news in August when it issued its Aggregate Production Quotas (APQs) for Schedule I and II controlled substances for 2018. (The list includes a group of ephedrine and pseudoephedrine Schedule I chemicals as well.) It has proposed to reduce overall volumes by 20%, citing the reduced amount of synthetic opioid prescription consumption in the US. The action, while legitimate and necessary, seems to be comparable to the Dutch boy with the finger in the dike, given the massive volumes of opioids being illegally conveyed into the country—including opioids counterfeited to appear like legitimate prescription drugs, which tend to have a higher street value.

It would seem reasonable that if opioid drugs were less easy to abuse, that abuse would decline. Purdue Pharma reformulated its extended-release Oxycontin with abuse deterrent features in 2010, and nearly all current Oxycontin prescriptions have been shifted over by now. But the jury is decidedly out on how abuse deterrent formulations (ADFs) would play out in the US healthcare system for other opioid formulations. Prescription opioid manufacturers (there are more than a dozen that belong to the Abuse Deterrence Coalition, a trade group) have been lobbying for legislation to compel FDA to shift opioid formulations to abuse-deterrent ones—but this has been happening without a law being passed.

FDA has allowed for “abuse deterrence” to be part of reformulated drugs’ label; there are currently nine so described, and another nine in late-stage FDA review. (One, Endo Pharma’s Opana, was to be withdrawn from the market in June, due to a review panel’s recommendation that its risks outweighed its benefits.)

A study published in August by the Institute for Clinical and Economic Review (ICER) paints a discouraging picture of the impact of ADFs on addiction. Clinical data on ADF abuse prevention is sketchy—the testing of such drugs involves trials with nonaddicted recreational drug users; and an ADF that works in the lab can be found to be subverted in the real world by techniques that quickly get shared among drug abusers. (One profoundly simple abuse is to take more of them at the same time.) ADFs are significantly more expensive than their non-reformulated, generic equivalents. ICER, which has established a reputation for rigorous comparative-effectiveness analysis, concluded that for every 100,000 chronic pain patients who are switched from traditional painkillers to an abuse-deterrent version, healthcare system costs would rise by $500 million over five years. Preventing even just one overdose death represents more than $1 billion in healthcare costs.

In press reports of the ICER study, Dan Cohen, head of the Abuse Deterrent Coalition, is quoted as saying “At its core, the report basically asked the question: Can these products do what they're not designed to do? Not surprisingly the answer is no,” noting that "They can't prevent addiction because they're not designed to prevent addiction.”

The market for therapeutic drugs for opioid addiction, while maintaining a pulse, is best characterized as “stunted.” Medication-assisted treatment (MAT) has been around for years—the earliest version was the methadone programs originally for heroin addicts. Now, Suboxone and various other products based on buprenorphine are available; however, most addiction centers still operate in the belief that abstinence is the best course of action, despite data from (among others) HHS that show beneficial outcomes from MAT programs.

Greg Sullivan, MD, is a physician that is board-certified in addiction medicine and has been a clinical trial investigator for the past 25 years, overseeing clinical trials, including safety and efficacy studies for every buprenorphine product currently approved for the US market. Many patients undergoing MAT, depending on the MAT medication, need to be carefully monitored, he says. Even though physicians can be certified (via a one-day course) to prescribe MAT using buprenorphine, relatively few have done so until recently. Similarly, only in recent years has federal regulation, specifically Data200, opened up pathways for addiction therapy, and have insurance companies provided coverage for MAT.

Dr. Sullivan is the co-founder of Bridge Therapeutics (Birmingham, AL), which is pursuing FDA approval of drug combination BT-205 for the treatment of chronic pain in opioid-experienced patients. The drug contains an NSAID, meloxicam, plus buprenorphine, a partial opioid agonist that has superior pain-relieving properties, is non-tolerance developing and is considerably safer than traditional opioids. BT-205 is targeted for chronic pain sufferers who need a solution to address their high levels of pain without becoming helplessly addicted—and whose only other prescription choices currently are full agonist (traditional) opioids, he says. Dr. Sullivan expects approval of the investigational drug in 2019 under the FDA’s 505(b)(2) approval process, which addresses new formulations of existing drugs. “Chronic pain affects more Americans than diabetes, heart disease and cancer combined, which means that—more than ever—providers need access to effective, safer and less addictive pharmaceutical treatments to help their patients.”

QuintilesIMS Compliance Solutions (formerly BuzzeoPDMA) has 

 on suspicious order monitoring; here are its five points for an effective SOM program:

 The model identifies orders that fit any of the three criteria:

orders of unusual size, orders deviating substantially from a normal pattern and orders of unusual frequency. The most defensible models are statistically based—employing advanced mathematics rather than arbitrary thresholds.

, including “Know Your Customer” activities. This can include a range of activities, such as questionnaires sent to customers and on-site visits that may be made initially, and even periodically, over time.

 Appropriate review and/or investigations

 of “pended” orders. Because labeling an order “suspicious” triggers a set of reporting requirements, QuintilesIMS recommends using a term like “pended” to indicate potentially suspicious orders. That way, an organization knows to launch its own internal investigation, which likely will include contacting the customer via phone and/or email.

 Clear, comprehensive SOM standard operating procedures

 (SOPs). Ensure that the organization has a methodology for how it manages SOM and the supporting processes.

 Management support and employee training.

 Finally, of course, is creating an environment of compliance. From management to front-line employees, the organizational culture should be committed to complying with all regulations, including SOM.

Commission issues interim report with numerous calls to action, while manufacturers and distributors contend with multiple DEA penalties

Is the opioid crisis a national emergency?

The pharma industry is well along in a shift

 from traditional mass-market drugs to specialties, which now represent 43% of net drug spending (invoice price less discounts), and which has doubled its proportion in overall drug spending over the past 10 years (QuintilesIMS statistics). One of the hallmarks of specialty drugs is the need for close interaction with patients, for initial diagnostics, ongoing patient support (financially, medically and psychologically) and outcomes analysis. The shift to value-based care will only intensify these interactions.

These trends flow in the same direction as the oft-claimed “consumerization” of healthcare, with consumers (patients) presumed to have a more direct hand in their own healthcare. On the medical research side, the genuine excitement around cellular and genetics-based therapies points to an era of personalized medicine, with drugs tailored to a patient’s individual genetic makeup.

Taken altogether, these trends call for a more-direct interaction between pharma companies and patients undergoing therapy. The industry has stepped up with a variety of patient support programs—internal support groups, outsourced hub services providers and closer interaction with patient advocacy organizations (some of which have undertaken their own drug development programs). On the whole, this is a beneficial arrangement: getting patients the right therapy, keeping them on therapy, and developing new drugs faster translates into better healthcare. It is often said that pharma companies are unsurpassed in knowing the details of how their drugs work and what patients they benefit; keeping that line of communication open is vital.

Now, however, there is growing anecdotal evidence of abuse of the pharma-patient interaction. With the latest specialty therapies (especially in orphan drugs), a single patient can represent several hundred thousand dollars in annual income for a pharma company. That’s a powerful incentive to identify potential patients and to be closely involved with their care—perhaps too closely. A 

Pharmaceutical Commerce - September/October 2017

Clearing the path by understanding the obstacles: The 2017 Sharing Conference

Patient data saves lives

MDM’s growing role in running healthcare businesses

The power of strategic data standardization

2017 Cold Chain Outlook

Cold Chain 2017 Directory

Is the opioid crisis a national emergency?

It’s time for an industry guideline on patient support services

A conversation with Greg Flynn, Ashfield Healthcare US

LogiPharma meeting highlights digital transformation

Drug development in rare diseases

‘Right to try’ programs see renewed legislative attention

HDA’s fourth international conference heads to Geneva

Change is a constant for sales incentive planning

New approaches to specialty distribution

ODA-designation application to approval in 19 days for Curtana Pharmaceuticals

The under-regulated world of patient services

Mylan finalizes a DoJ settlement over EpiPen pricing

Post-approval trials of new drugs are showing limited clinical value

CVS readies a set of outcomes-based contracts for its clients

EMA entertains relocation bids, readies a business-continuity plan