![](media/image1.jpeg){width="1.3833333333333333in"
height="0.3423611111111111in"}McKesson Corporation

One Post Street

San Francisco, CA 94104-5296

![](media/image2.jpeg){width="0.25in" height="0.15in"}

April 30, 2003

Dockets Management Branch (HFA-305)

Food and Drug Administration

5630 Fishers Lane, Room 1061

Rockville, MD 20852

> **RE: Comments on Risk Management Programs Concept**
>
> **\[Docket No. 02N-0528\]**

Dear Sir or Madam:

McKesson Corporation (hereafter \"McKesson\") appreciates the
opportunity to provide comment on the *Risk Management Programs Concept
Paper* (docket number 02N-0528) published by the Food and Drug
Administration ("FDA") on March 7, 2003. McKesson commends the
Administration\'s efforts to seek industry input on the design of a risk
management program in an effort to maximize the benefit and reduce the
risks associated with the use of pharmaceutical and biotechnology
products. This is an important step toward improving patient safety,
while facilitating the appropriate introduction of new, life-saving
therapies.

We attended FDA's April 10, 2003 Risk Management Public Workshop and
noted with great interest the breadth of stakeholders and their comments
regarding the FDA's risk management initiatives. As the FDA has noted, a
risk management program can be designed to either *facilitate* or
*constrain* the target audience. It has been our experience that it is
important to maintain an appropriate balance between these two
techniques to facilitate optimal patient care. We agree that the primary
focus of these tools is prescribing physicians, dispensing pharmacies
and patients. However, we believe it is also important to consider the
role other healthcare delivery system stakeholders including payers,
pharmacy benefit managers ("PBMs"), pharmaceutical distributors, other
healthcare professionals have in improving patient outcomes. Their
requirements should also be evaluated whenever possible to promote an
optimal implementation.

McKesson is a *Fortune* 20 corporation and the world\'s largest
healthcare information technology and services company. McKesson
provides a full range of supply management solutions and information
technologies that are designed to improve performance across the entire
continuum of healthcare. Our market-leading businesses include
healthcare information systems; patient services such as patient
assistance, patient resource centers, and disease management programs;
pharmaceutical and medical-surgical distribution; automation; healthcare
information systems; and medical management products and services. As
one of the largest nationwide distributors of pharmaceuticals and
medical-surgical products to pharmacies and other health care providers,
we serve as the interface between the pharmaceutical manufacturing and
retail pharmacy community. McKesson's Health Solutions subsidiary
occupies a unique position in the pharmaceutical care system. Working in
conjunction with patients, physicians and dispensing pharmacy providers,
this division provides services related to the manufacturer and
distribution components of pharmaceutical care delivery. In addition,
this group coordinates programs and services with a broad array of
payers, PBMs and other fiscal intermediaries to coordinate various
reimbursement-related services for pharmaceutical and biotechnology
products.

Our unique footprint in healthcare and broad array of industry touch
points offers us a unique perspective of the healthcare system and how
technology can be deployed to meet the needs of all stakeholders. We
understand the diverse platform that is required for more effective
program administration and data collection and have first hand
understanding of how an effectively designed risk management program can
improve patient care. Our experience includes the design and operation
of managed distribution and patient support programs for beta
interferon, human growth hormone, etanercept and alpha interferon at
various stages of clinical development and post-approval. Each of these
products and their corresponding programs were unique, with unique
storage, distribution, product administration, reimbursement and patient
support needs.

McKesson offers these comments based upon our firsthand experience with
those program components that work well, and the dramatic impact of
seemingly minor details on effective program administration.

**[1. Risk Management Concepts (Sect. II, lines 16 -- 35 -- page
2)]{.underline}**

We agree with the FDA comments that optimizing the benefit / risk
balance associated with patient drug use is a continuous learning
process. Our cumulative experience with providing managed distribution
systems for biopharmaceutical manufacturers over the past ten years has
proven invaluable in the design and administration of subsequent
programs. We encourage the FDA to continue to seek out the experience of
other stakeholders. Changing program dynamics often require a quick
implementation of appropriate interventions. Although new biotechnology
products have revolutionized the treatment of several diseases over the
past decade, our daily patient interactions suggested early on that a
comprehensive program for patient training in self-injection was
critical in removing this barrier to initiation of therapy.
Interestingly, these improved techniques result in reduced adverse
reactions, improved compliance and persistency, and ultimately patient
outcomes. By taking a drug-by-drug, program-by-program approach, unique
patient and program needs can be considered and often accommodated.

**[2. Comprehensive, Coordinated RM Planning (Sect. II, lines 40 -- 45
-- page 3)]{.underline}**

McKesson shares the FDA vision of a comprehensive approach to risk
management planning which also includes good risk assessment practices
during the clinical development phase, and appropriate pharmacovigilance
practices and assessment of observational data. While we are not
offering specific comments to these concept papers, we echo the comments
voiced by several meeting participants that these initiatives, while
distinct in their design and overall goals, should be integrated
whenever possible. We believe one key to addressing this challenge of
coordinated risk management planning is to clarify how a technological
approach and comprehensive, flexible, platform design can support both
the varied needs of successful drug risk management programs and the
broader risk management planning process. While, as noted by one
speaker, the RM tool could be viewed as the "Achilles Heel" of the FDA's
risk management initiatives, we believe it can also serve to unify these
three distinct program components. This framework not only provides
needed direction to pharmaceutical and biotechnology manufacturers; it
can also be helpful in the risk assessment phase by clarifying how a
given tool or intervention might be operationalized and deployed. Such a
tool could be an invaluable resource in the transition of a product from
Phase III clinical studies to Phase IV surveillance. Likewise, this tool
could also provide a framework for identification of product safety
signals and development of a pharmacovigilance platform.

**[3. Human/Institutional Factors (Sect. II, starting line 76 -- page
3)]{.underline}**

McKesson's experience is consistent with the FDA's belief that a risk
management program should consider critical processes, behaviors and
human factors of targeted stakeholders.

*Patient*

Our experience suggests factors such as patient education, language and
socioeconomic background are critical factors in the success or failure
of therapy. For example, a risk management program will be more
effective in influencing compliance for a Spanish- speaking patient if
the program has integrated Spanish-speaking nurses that can communicate
effectively with the patient. Similarly, nurses trained in methods of
communicating at varying levels of sophistication will be more effective
in influencing compliance of patients from different educational
backgrounds.

*Physicians*

It is important to consider the varying processes, behaviors and
practice infrastructure of prescribing physicians. For example,
physician office training of patient self-injection is less commonplace
with neurologists, which usually do not have appropriate support
processes or personnel, than with endocrinologists who will often train
diabetics regarding insulin injections. Similarly, the desired
communications channel might differ between a busy infectious disease
physician and a research-based geneticist in a teaching setting that
treats rare genetic disorders.

*Pharmacies*

The most effective method of communicating with various types of
pharmacies differs, and it is important to understand these dynamics to
ensure a consistent message. Chain pharmacies, for example, tend to have
centralized methods of communication, and the most effective way to
communicate to these providers is often through the corporate chain
headquarters. Likewise, a blast fax may be a more rapid and effective
means of communicating critical information to independent community
pharmacies.

**[4. Current Risk Management Program Tools (Sect. III, lines 175 -- 213
-- page 6)]{.underline}**

The FDA concept paper describes and categorizes many of the tools that
are currently in use to promote the safe use of drug products. While
acknowledging FDA authority and responsibility for the ultimate
selection and implementation of risk management tool(s), we submit our
perspective regarding some of these existing interventions.

# [Education and Outreach]{.underline} 

As noted earlier, effective communications to healthcare professionals
and patients must take into consideration the diversity of these
audiences, their frame of reference, potential language barriers,
differences in physician specialties, practice settings and
socioeconomic factors. Our experience suggests that multiple methods of
communication are necessary to effectively reach physicians, pharmacies
and patients. In addition, use of more than one communication channel
(phone, facsimile, web, print) increases the likelihood of reaching the
intended audience.

[Passive Prescribing & Dispensing Controls]{.underline}

The use of patient agreements and documentation of informed consent are
useful tools that help promote better patient understanding and
attenuate the risks associated with the use of a drug. Ideally, these
records should be maintained in a centralized, electronic repository
where they can be readily accessed, verified and updated as required,
rather than a decentralized, paper-based file in each prescribing
physician's office. This is of even greater importance today with the
implementation of the Health Insurance Portability and Accountability
Act of 1996 (HIPAA) and its associated requirements. McKesson's
experience includes multiple programs requiring the enrollment of
patients, prescribing physicians and dispensing pharmacies, and we can
attest to the wealth of information that can be obtained when these
processes and enrollment data are integrated with electronic systems
that authorize and capture key dispensing event data (prescribing
physician, patient, pharmacy, quantity, days supply and refills).

[Restricted Access Systems]{.underline}

While restricted access systems are highly effective in enforcing
compliance with a risk management program, McKesson endorses an approach
that allows participation by any dispensing pharmacy provider willing to
meet the terms and conditions of program participation, rather than a
system that uses a single or limited number of pharmacy providers. We
believe that a risk management tool that incorporates broad pharmacy
access removes a potential barrier to patient use by improving patient
access, and promotes greater continuity of care by allowing patients to
use the pharmacy of their choice for all of their pharmaceutical needs.

**[5. Effective RM Tools (Sect. III, line 225 -- 240 -- page 7) Lines
229 -- 231]{.underline}**

We agree that it is important to consider input from key stakeholders,
such as those identified in the Concept Paper (Sect. III, lines 229 --
230 - page 7), on the feasibility of implementing and accepting the
tools in usual healthcare practices, disease conditions, or lifestyles
when choosing the most effective tools. We would like to add that the
varied nature of these stakeholders' respective practice settings should
also be considered.

Varying types of pharmacies, such as mail order pharmacies, specialty
pharmacies and infusion pharmacies will have unique processes and
requirements. A risk management protocol incorporating quantity
restrictions of a 30-day supply will not impact a traditional retail
pharmacy setting, but does not fit into the standard processes and
prescription plan designs of mail order pharmacies whose business model
is based upon dispensing larger quantities.

Similarly, protocols, processes and requirements differ by various third
party payers, such as commercial healthcare insurers, managed care
organizations, Medicaid, Medicare and other federal programs such as
Department of Defense and Veterans Administration. A risk management
program that impacts Medicaid patients must coordinate Medicaid pharmacy
provider services in each of the 50 states.

## Lines 232 -- 233

We agree with the FDA's assessment that the most effective tools will be
consistent with existing tools that are familiar to and accepted by
targeted groups. We believe it is important that a risk management
program not disrupt the daily processes that the target groups already
have in place. For example, while the internet may generally be an
effective medium of disseminating information, many pharmacies are
either not internet enabled, or do not regularly utilize the internet.
Therefore, a tool that relies upon pharmacists to electronically capture
or record information via the communication channel may be less
effective than alternative methods.

## Lines 236 -- 238

We agree that documented evidence of effectiveness that supports
rationale, design, or method of use should be considered in choosing the
most effective tool. As described earlier, a patient injection-training
program offered through skilled nurses was found to result in fewer
adverse reactions and increased patient compliance.

## 

## Line 239

We believe that a well-designed platform of RM tools will reduce the
program variability and increase the repeatability of desired results.
As several speakers noted during the FDA Workshop, many existing RM
tools such as "sticker programs" are viewed by stakeholders as
cumbersome, labor intensive and time consuming. It is our view that a
more effective tool would reduce reliance upon such paper-based systems
and would deploy information technology to simplify administration.
Equally important, an information technology system would generate
valuable information at the physician, patient, product and dispensing
level for FDA and manufacturers' use. Such a technology platform
approach would have the flexibility to incorporate varied interventions
or tools that are needed for a particular product.

**[6. Risk Management Program Categorization (Sect. III, lines 253 --
260 -- page 7)]{.underline}**

McKesson commends FDA's proposed approach to assigning levels of risk
management for biopharmaceuticals to promote patient safety. We believe
such a program would, where appropriate, accelerate the product approval
process and promote the introduction of new, novel therapies used to
treat life-threatening illness, while addressing the important issues
surrounding patient safety. While we understand biopharmaceutical
industry concerns that a RMP leveling system might result in a stigma
associated with the product, this risk is significantly over-shadowed by
the substantial increase in patient safety.

**[7. Evaluation Methods (Sect. III, lines 366 -- 384 -- page
10)]{.underline}**

McKesson's experience with collecting adverse event data and claims data
supports FDA's concerns regarding strengths, weaknesses and merits of
different evaluation methods. First, McKesson's experience emphasizes
the importance of differentiating between stimulated and non-stimulated
adverse events. For example, a call center scripting system that manages
communications to patients will avoid inadvertent stimulation of adverse
event reports and maintain message consistency.

Second, we are familiar with the limitations of relying upon fragmented
sources of claims data. For example, purchased claims files constitute a
limited universe of patient data. Through our experience administering
pharmaceutical managed distribution programs, we have learned the
tremendous value of rich patient data generated by an independent, fully
inclusive and all encompassing database. The database generated by such
a program provides a robust source of information for the ongoing
management, evaluation and revision of a risk management program.

McKesson envisions a flexible, technology-based platform from which
various risk management tools can be deployed to meet the unique program
objectives that will invariably be associated with each drug product.
From this platform, we believe customized, comprehensive, integrated and
inclusive risk management tools can be designed and implemented as the
need arises to effectively work within the complex U.S. healthcare
system. The following diagram, while depicting a somewhat oversimplified
system of the pharmaceutical care system, illustrates this concept:

Figure 1

![](media/image3.wmf){width="5.3in" height="3.4604166666666667in"}

While any risk management program must focus primarily on the
pharmaceutical care component of this model, it is also important to
consider associated distribution and reimbursement processes. Varying
policies and requirements of Medicare, Medicaid, managed care and
commercial insurers must be considered. Risk management tools for
products covered under an outpatient prescription drug benefit
administered by a PBM will have different considerations than those
products covered under a major medical benefit. A program that limits
dispensed quantities to monthly supplies, while easily accommodated in a
community pharmacy setting, conflicts with normal mail service pharmacy
routines that dispense three-month supplies. Likewise, each of these
dispensing pharmacies has differing drug purchasing and distribution
processes and relationships. Under most circumstances, this distribution
component must be coordinated with one of the dozens of pharmaceutical
wholesalers from which a pharmacy selects as their prime vendor for drug
purchases. Similarly, some programs may not interact with traditional
dispensing pharmacies, based upon the distribution channel and site of
care. For example, a risk management tool associated with a product that
is administered via infusion in a physician's office or alternate care
facility will have different characteristics than a tool associated with
a drug ordinarily dispensed in a community pharmacy setting.

Figure 2

![](media/image4.wmf){width="6.229861111111111in"
height="4.1722222222222225in"}

As illustrated in Figure 2 above, one way to conceptualize this risk
management platform and its associated toolbox of interventions is to
view it from a technology infrastructure, the requisite operational
interfaces within the pharmaceutical care model, and the programs,
processes, functionality and services that are associated with these
various integration points.

Figure 3

![](media/image5.wmf){width="4.9in" height="3.7881944444444446in"}

Figure 3 illustrates with greater detail the technology infrastructure
and some of the systems, databases, services and metrics that could be
associated with a risk management program. One key result of this
approach is an integrated data warehouse that can become a
stepping-stone to a complete clinical surveillance and evaluation tool.

Figure 4

![](media/image6.wmf){width="5.629861111111111in"
height="4.129166666666666in"}

# 

McKesson appreciates the opportunity to comment on FDA's Risk Management
Concept Paper. We are pleased that the Administration is taking
appropriate steps to improve patient safety, while considering the
unique risk / benefit profiles of pharmaceutical therapies. We believe
that a technology based, inclusive risk management program that
accommodates the practice settings, systems, operations and processes of
the various stakeholders in the pharmaceutical care system will most
effectively achieve this objective.

Although no model currently exists, much of the technology and
infrastructure exists and is operating today. We believe that a platform
as depicted above can also assist in the critical task of a completely
integrated risk management solution, inclusive of risk assessment and
pharmacovigilance. McKesson stands ready to assist the Administration
and the healthcare industry in accomplishing these risk management
initiatives.

Sincerely,

![](media/image7.png){width="2.5125in" height="0.5694444444444444in"}

Ann Richardson Berkey

Vice President Public Affairs

McKesson Corporation