Clinical Operations (PH152)

Clinical Operations Report Sample

The following excerpt is taken from Chapter 2, “Clinical Trial
Staffing Benchmarks.” It outlines the information contained
within this section of thereport. For complete access to
detailed benchmarks, please purchase the full report.

Staffing Levels for Development Phases

This section includes detailed staffing benchmarks for each of the five phases of
clinical trials: Phase 1, Phase 2, Phase 3a, Phase 3b and Phase 4. In addition,
the staffing data included in this section are broken down into 12 occupational
categories. Each represents a unique role in the clinical development process.

Although many of these development functions are members of trial teams at
most companies, not all companies analyzed for this study organize their clinical
development teams in the same manner. As such, some functions — such as
clinical trial supplies, chemistry manufacturing and controls (CMC), and drug
safety — often play a supporting role in the clinical development process even
though they may not sit on trial teams. In each category, the data tables present
staffing metrics for both in-house and outsourced staff. These are the 12
categories:

• CRAs/Monitors
• Trial Managers
• Vice Presidents, Clinical Program Directors, and other such therapeutic
  area supervisors
• Data Management
• Medical Writing
• Biostatistics/Bioanalytics
• Regulatory
• Clinical Quality Assurance (QA)
• Clinical Trial Supplies
• Chemistry Manufacturing and Controls (CMC)
• Contract Management
• Drug Safety

The data contained in each of the 12 categories represent peak staffing levels for
the development phase, as measured in full-time equivalents (FTEs). FTEs do not
always correspond to the number of people actually working on a certain task.
One FTE, for example, may equate to two people spending 50% of their time each
on the task.

The data tables [available in the full report] present actual staffing levels
for clinical trials in each phase. Each staffing table includes the following
information about each trial:

• Therapeutic area
• Study location(s)
• Number of patients enrolled
• Number of investigator sites

These four factors act as important guides to enable readers to compare staffing
trends between trials.

Clinical Trial Staffing: Phase 1

Data in the figures from Chapter 2 [available in the full report]
represent nine Phase 1 clinical studies from these therapeutic areas:

• Cardiovascular Disease
• Central Nervous System/Neurology
• Diabetes
• Endocrinology
• Oncology

Overall, Phase 1 clinical trials employ the fewest number of FTEs and outsource
the lowest percentage of staff. Figure 2.5 shows this clearly: the data show that
the largest staffing categories are CRA/monitor and data management, but they
still only account for an average of 3.1 FTEs and 2.5 FTEs, respectively. With an
average of 3.1 CRAs per trial, Phase 1 ranks lowest among all other phases.

The following excerpt is taken from Chapter 4, “Adaptive Clinical Trial Design.”
The full chapter provides a comprehensive analysis of adaptive design. It
includes a detailed discussion on the FDA’s new guidance, as well as
benchmarks showing adaptive design usage and its impact on time and cost.

Reaction to FDA Guidance

On its face, the guidance provides a cautious endorsement of adaptive design
as a method for accelerating the development process and increasing the
efficiency of clinical trials. However, the reality — as shown in Figure 4.3 [available in the full report] — is that it is used infrequently at all stages of clinical
development, especially in critical Phase 3 trials. Figure 4.4 shows survey
respondents’ perceptions of the likelihood of introducing adaptive design into
trials at various phases of development, rating each on a scale of one to five
(with five representing very likely). Respondents identified Phase 2 as the most
probable place to use adaptive design, followed by Phase 3b. During interviews,
industry experts noted that Phase 3b trials, typically follow-ups to already
successful confirmatory studies, are ripe for adaptive design because companies
are pushing to get an approval they are confident will occur, and time- and costsaving
tactics are at a premium.

The question of when pharma will begin to put adaptive design to use in Phase 3a
trials more frequently will hinge on the success — or failure — of some of the early
adopters of the technique. Until a high-profile drug approval is won with adaptive
design incorporated into the Phase 3 protocol, trepidation will remain.
“I think the FDA needs to clarify what their position is. Because in spite of what
is in the guidance...the reviewing divisions have made it clear that they’re still
uncomfortable with anything that happens to the data that might compromise
the integrity of the data or introduce bias,” said the regulatory affairs manager at
Company C.

He continued:

So I think frankly that a number of sponsors would entertain the idea of doing adaptive
design in Phase 3 studies, particularly if you’re doing the so-called seamless Phase 2-3.
They’re concerned that at the end of the day, the reviewers are going to come back and
say you unblinded the data too early, the study wasn’t over, etc., so there’s a chance that
bias has been introduced and you’re going to have to take either a statistical hit or do
something that will compromise your ability to gain an approval easily. I think it really is a
question to a certain extent of mixed messages.

The statistical review personnel at the FDA view adaptive design as a major technical
advance, but long-tenured regulatory personnel have a less favorable view of the new
technology and are less likely to fully support it. In response, clinical directors are
reluctant to take a perceived risk with adaptive trial designs that may not serve the
company’s goal of getting a drug to market as quickly as possible.