Post-Marketing Study Excellence (PH220)

Design Phase 4 Trials to Demonstrate Real-World Outcomes
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Published 2016
275 Pages
500+ Metrics
200+ Charts and Diagrams

Phase 4 and Post-Marketing Studies: Improve Late-Stage Team Performance

For pharmaceutical companies’ products to maintain market authorization and continue to earn product reimbursement and market share, Phase 4 and post-marketing studies provide an ideal opportunity. Companies need to conduct late-stage studies to investigate product effectiveness, health economic outcomes, product utilization and other key data not readily collected in Phase 3 trials.

Cutting Edge Information’s Phase 4 research report, Post-Marketing Study Excellence, is designed to improve post-marketing teams’ performance when conducting studies. This report analyzes the percentage of post-marketing studies that adhere to different Data also covers retrospective studies. The report’s data were compiled from global, US and country-level teams for Top 10, Top 50, and small pharma and biotech companies, as well as medical device companies.

The following principles are signposts to help improve your company’s Phase 4 and post-marketing studies:

  • Leverage medical affairs’ expertise to guide post-marketing study development.
  • Consider number of post-marketing studies per product when planning team strategies.
  • Outsource post-marketing study activities to decrease average duration from protocol design to training.
  • Be aware of the implications of providing patients with the product in observational trials.
  • Consider team region when determining Phase 4 study objectives.

 

Key Questions That This Study Answers About Post-Marketing Studies

  • What strategies can our team implement to improve cross-functional communication and coordination for post-marketing studies? How can we leverage medical affairs and clinical teams to accelerate timelines and lower costs?
  • Which activities should be left in-house vs. outsourced to shorten Phase 4 study timelines?
  • How can new technologies and trends, including mHealth and real-world data, facilitate post-marketing study obstacles, such as patient recruitment? What impact do these new trends have on regulatory concerns and payers?
  • How can companies improve study designs and identify primary research objectives to avoid unnecessary data collection?
  • How can companies best prepare for and ensure efficient post-marketing studies – interventional, observational and retrospective?
  • How much time should be spent on selecting vendors for interventional studies?
  • How much time should be spent training investigators in the different interventional study types (e.g., pragmatic, crossover or large sample)?
  • How many staff are needed to successfully run an observational trial? What is an ideal ratio of patients per investigator site for observational studies?

What are the benefits of retrospective studies, and how can teams overcome obstacles unique to studies of this type? How can teams also reduce associated costs for retrospective studies?
 

Top Reasons to Read This Report

Benchmark your post-marketing and Phase 4 trial timelines: One critical measure of post-marketing study productivity is the trial timeline. Time is money, and unreasonably long timelines both hurt the company financially and could hurt the studied product’s market position should competitors collect late-stage data faster. The study includes detailed metrics to benchmark your study timelines against the typical duration for interventional, observational and retrospective trials. 

Compare relative study costs to determine future spending: Although Phase 4 and post-marketing study cost is not the primary consideration for pursuing a specific trial, it is an important factor. The report’s data show percentage of annual costs allocated to different post-marketing study types. It also compares study costs for interventional, observational and retrospective among Top 10, Top 50 and small pharmaceutical companies. The data are also broken down to show costs for global, US, European and Latin American regions.

Leverage medical affairs’ expertise to guide post-marketing study development:
This report provides an in-depth discussion regarding companies’ general post-marketing study structures, including the functions involved and the responsibilities they undertake. The study includes a particular focus on medical affairs teams, who often provide additional guidance on Phase 4 activities. In fact, among all companies surveyed, medical affairs functions overwhelmingly handle the planning aspect of post-marketing research. The study found that surveyed life science teams with 78% of dedicated post-marketing study groups are aligned under medical affairs.

Outsource post-marketing study activities to decrease average duration from protocol design to training: A common point of discussion is whether the sponsor company should outsource its Phase 4 and post-marketing studies. After all, outsourcing certain activities can provide efficiency and speed during Phase 4. This report breaks down the most commonly outsourced post-marketing study activities, as well as those activities which make more sense to retain in-house.

Post-Marketing Study Metrics

 

Chapter 1: Promote Efficient Phase 4 Oversight Capabilities with Robust Post-Marketing Structures and Staffing

Major Takeaways

  • Involve medical affairs in Phase 4 planning and execution to conduct studies faster and at a lower cost.
  • Clearly delineate individual teams’ responsibilities and communicate project timelines.
  • Develop feasibility assessments as a springboard for post-marketing strategy and to determine how potential studies may address multiple functions’ needs.

 
Chapter Data

6 charts detailing postmarking team structure, reporting lines and scope of responsibility. Throughout the chapter, data are broken down by company size (Top 10, Top 50, and small pharma) and team region (global, US, and country-level).

  • Function under which dedicated post-marketing studies teams sit
  • Post-marketing studies groups’ scope of responsibility at surveyed companies
  • Functions involved in certain post-marketing study activities
  • Percentage of teams with certain functions involved in study strategic planning and execution

 

Chapter 2: Resourcing and Staffing Post-Marketing Studies

Major Takeaways

  • Outsource protocol development to shorten Phase 4 trial timelines.

 
Chapter Data

21 charts detailing the annual budgets necessary to support three types of post-marketing studies — interventional, observational and retrospective — each year. Further data highlight study team overhead, salary costs and team staffing. Throughout the chapter, data are broken down by company size (Top 10, Top 50, and small pharma) and team region (global, US, and country-level).

  • Post-marketing study costs for 2014–16 (by team region)
  • Total study costs, by year (2014–16), for interventional, observational and retrospective studies
  • Post-marketing study team salaries and overhead costs (by team region)
  • Post-marketing study team size for 2014–16 (by team region)
  • Percentage change in post-marketing team staffing (by team region)
  • Percentage of actual study costs outsourced (by study type)
  • Comparing timelines and outsourcing practices
    • Protocol development
    • Investigator and site recruitment
    • Investigator and site contract negotiations
    • Investigator and site training

 

Chapter 3: Post-Marketing Study Trends

Major Takeaways

  • Use social media and/or mHealth to expedite patient enrollment and data collection.
  • Track study timelines to show team efficiency and areas for improvement.
  • When designing a trial, consider the primary research objectives for a product to avoid collecting unnecessary data.
  • Plan the number of studies your team will conduct by comparing data about the average number of studies per product.

 
Chapter Data

32 charts detailing post-marketing study strategies, planning, timelines and trends. Throughout the chapter, data are broken down by company size (Top 10, Top 50, and small pharma) and team region (global, US, and country-level).

  • Percentage of studies requiring an IND, by study type
  • Range and average number of days spent from:
    • Study planning to submission of manuscript for publication
    • Study planning to first patient in study
  • Primary objectives for post-marketing studies (by study type and product type)
  • Stage when post-marketing study planning and execution begins (by product type)
  • Total and average number of studies per product for 2014, 2015 and 2016 (by company and team region)
  • Average percentage of post-marketing studies that are certain study types for 2014–16 (by team region)

Number of post-marketing studies conducted in 2014, 2015 and 2106 by study type (interventional, observational and retrospective)

 

Chapter 4: Diversify Interventional Study Designs to Yield Informative Clinical Findings

Major Takeaways

  • Select an interventional study design that best fits your primary research objective.
  • Set aside about 2 months for vendor selection for interventional studies.
  • Plan to spend more time training investigators for pragmatic, crossover and large simple safety trials than for traditional RCTs.

 
Chapter Data

38 charts detailing data from interventional trial case studies; data focus on patient enrollment, trial objectives, resources and timelines. Data are divided based on the type of trial design, such as traditional random controlled trial (RCT), pragmatic RCT, crossover or large simple trials.

  • Percentage of teams conducting interventional studies for 2014–16
  • Percentage of interventional studies that include retrospective data
  • Average percentage of interventional studies following particular trial designs:
    • Traditional RCTs
    • Large simple trials
    • Pragmatic RCTs
    • Crossover studies
    • Aggregated n-of-1 studies
  • Objectives for traditional RCT trials
  • Percentage of target patient enrollment achieved: interventional studies
  • Number of patients per site: interventional studies
  • Difference in planned and actual study costs: interventional studies
  • Percentage of actual study costs outsourced: interventional studies
  • Percentage of interventional studies that outsource certain items
  • Number of days spent recruiting and selecting vendors: interventional studies
  • Number of days spent negotiating vendor contracts: interventional studies
  • Total staffing for interventional studies
  • Stage when study planning and execution begins: interventional studies
  • Number of days spent from:
    • Study planning to first patient in
    • First patient in to last patient in
    • Last patient in to data lock
    • Data lock to submission of manuscript for publication
    • Training investigators and sites

Interventional Study Profiles

Chapter 4 provides profiles for five interventional studies.

Section 1: Study Background

  • Team region
  • Company size
  • Therapeutic area
  • Product type
  • Study type
  • Primary study objective

The background page also illustrates the study’s target patient enrollment, actual patient enrollment, and the number of investigator sites. Finally, this page highlights different study features, such as:

  • Did the study require an IND?
  • Did the study use retrospective data?
  • Did the study use mobile technology to collect data or recruit patients?
  • Did the study use social media to recruit patients?

Page 2: Study Costs

  • Study’s planned and actual costs and the percentage difference between these two
  • Percentage of actual study cost outsourced and the specific items outsourced for the study

Page 3: Trial Staffing

Trial staffing for interventional studies is divided into 14 different groups. Staffing is also divided into in-house and outsourced FTEs.

Page 4: Study Timeline

  • The last page describes the study’s timeline as well as the number

 

 

Chapter 5: Explore Real-World Data with Observational Studies

Major Takeaways

  • Use benchmarks to right-size observational study staffing; staffing an observational study often involves fewer than 15 FTEs.
  • Plan to have between 3 and 25 patients per investigator site for observational studies.

 
Chapter Data

35 charts examining trends among surveyed life science organizations and select observational studies. Data examine the prevalence of specific observational trial designs — cohort, case-control or cross-sectional studies — among surveyed studies, as well as the prevalence of specific trial objectives.

  • Percentage of teams conducting observational studies, by year (2014–16)
  • Percentage of observational studies that include retrospective data
  • Average percentage of observational studies following particular trial designs
  • Percentage of observational studies with certain objectives, by study design
  • Percentage of target patient enrollment achieved: observational studies
  • Number of patients per site: observational studies
  • Percentage of companies providing the product to patients for observational studies
  • Difference in planned and actual study costs: observational studies
  • Percentage of actual study costs outsourced: observational studies
  • Percentage of observational studies that outsource certain items (e.g., data analysis, data management, trial monitoring)
  • Number of days spent:
    • Recruiting and selecting vendors
    • Negotiating vendor contracts
    • From study planning to first patient in
    • From first patient in to last patient in
    • From last patient in to data lock: observational studies
    • From data lock to submission of manuscript for publication
    • Training investigators and sites
  • Total staffing for observational studies


Observational Study Profiles

This section profiles four surveyed post-marketing observational studies. Study profiles are organized based on the type of team conducting the study as well as by:

Section 1: Study Background

  • Team region
  • Company size
  • Therapeutic area
  • Product type
  • Study type
  • Primary study objective

The background page also illustrates the study’s target patient enrollment, actual patient enrollment, and the number of investigator sites. Finally, this page highlights different study features, such as:

  • Did the study require an IND?
  • Did the study use retrospective data?
  • Did the study use mobile technology to collect data or recruit patients?
  • Did the study use social media to recruit patients?

Page 2: Study Costs

  • Study’s planned and actual costs and the percentage difference between these two
  • Percentage of actual study cost outsourced and the specific items outsourced for the study

Page 3: Trial Staffing

Trial staffing for interventional studies is divided into 13 different groups. Staffing is also divided into in-house and outsourced FTEs.

Page 4: Study Timeline

  • The last page describes the study’s timeline as well as the number

 

Chapter 6: Maximize Retrospective Study Outcomes Through Early Planning

Major Takeaways

  • Don’t reinvent the wheel (conduct another prospective study) when retrospective data is available and will meet desired Phase 4 study objectives.
  • Retain at least some level of retrospective study activity in-house to limit associated costs.

 
Chapter Data

29 charts detailing an overview of the budgets, staffing and data resources necessary to support post-marketing retrospective studies.   This chapter also outlines some of the guiding objectives behind companies’ increased use of retrospective study designs.

  • Percentage of teams conducting retrospective studies, by year (2014–16)
  • Source of data for retrospective studies
  • Objectives for retrospective studies
  • Difference in planned and actual study costs
  • Percentage of actual study costs outsourced: retrospective studies
  • Percentage of retrospective studies that outsource certain items (e.g., data analysis, data management, trial monitoring)
  • Number of days spent:
    • Recruiting and selecting vendors
    • Negotiating vendor contracts
    • Study planning and execution
    • From study planning to protocol approval
    • From protocol approval to data lock
    • From data lock to submission of manuscript for publication
  • Total staffing for retrospective studies

Retrospective Study Profiles

Study profiles are organized based on the type of team conducting the study as well as by:

  • Product type
  • Therapeutic area
  • Data source
  • Study objective

Profiles detail study resource allocations, including planned and actual budget comparisons, percentage of costs outsourced and total in-house and outsourced staffing. Each profile also outlines responsibilities that each study team outsourced during its retrospective trial. The final page of each study profile describes the number of days necessary to achieve the following clinical trial milestones:

  • Study planning to protocol approval
  • Protocol approval to data lock
  • Data lock to completed statistical tables
  • Completed statistical tables to clinical trial report submission
  • Clinical trial report submission to publication manuscript submission

SAMPLE CONTENT FROM Post-Marketing Study Excellence

The following excerpt is from Chapter 3, Post-Marketing Study Trends.

DEALING WITH GOVERNMENT REGULATIONS

Government regulations play a large role in post-marketing studies. Agency guidelines determine whether or not a study classifies as interventional or observational, and these distinctions can affect ethics discussions and Good Clinical Practice (GCP). European guidelines regarding study classifications seem to be either a struggle or a boon for interviewed executives. Meanwhile, in the US, teams are slowly getting accustomed to the Physician Payment Sunshine Act protocols. Finally, some studies in the US require Investigational New Drug (IND) applications, requiring teams to work with their regulatory affairs group to help with filing.

DEFINING OBSERVATIONAL STUDIES

An interesting — if not frustrating — trend in the regulatory and ethics world is how to define observational studies. It seems like it would be a straightforward distinction, but there are some observational studies that have very low levels of intervention. It is important — both from a GCP and ethics standpoint — to clearly define these studies.

According to an interviewed executive at Company E, some observational studies may be defined as interventional based on some guidelines. The executive explained, “In Europe, they continue to update the regulations around real-world studies, and every time they update it I think it becomes grayer.” These so-called “gray areas” or unclear categories make it difficult for teams to decide how to present these studies to ethics committees. Problems with the ethics committee or any other regulatory concerns can delay trial timelines, so teams would do well to educate themselves about these guidelines to improve their study categorizations.

However, teams that focus on vaccines do not seem to be facing this problem. Company A sometimes conducts observational studies with low intervention, and it celebrates that there are a lot of discussions about clarifying what “low intervention” actually is. Beginning with its Guideline on Clinical Evaluation of New Vaccines in 2006, the EMA has continued to clarify the intent of vaccine Phase 4 studies, according to an executive at Company A. She continued, “For us, it’s very good because the guidelines and discussions will help us a lot.”

Phase IV Clinical Trials Report Sample


The following excerpt is taken from Chapter 1, “Study Management Structure, Oversight and Strategy.” It discusses departmental roles for setting Phase IV strategy among companies in the US and the EU using examples from surveyed companies. The full chapter explores the spectrum of post-marketing study management structures in place across the industry, citing benefits and disadvantages for each. It also explores oversight for Phase IV strategy and execution. Finally, it contains patient enrollment benchmarks for five different Phase IV trial types across seven different therapeutic areas.

 

Set Phase IV Study Strategy Within the Medical Affairs Function

 

Today, medical affairs teams remain the dominant players who set the strategy for Phase IV studies, but decisions are not made in a vacuum. Several other corporate functions impact strategy. According to Figure 1.17, 72% of surveyed companies indicate that their medical affairs teams play a role in the development of Phase IV clinical strategy. But clinical and marketing teams widely maintain influence on Phase IV strategy development. Clinical teams impact strategy development at half of all surveyed companies, while marketing teams are involved at 44% of all surveyed companies.

When survey responses are broken out into US and European data, patterns emerge. US pharmaceutical companies ask fewer functional groups to take part in the development of a corporate Phase 4 strategy than do European companies. Half of the US companies surveyed (Figure 1.18 [not shown]) use only one department to set Phase IV strategy; two companies use medical affairs and two companies use clinical development.

In contrast, European companies (Figure 1.19 [not shown]) employ a committee approach to strategy development. Of the 10 surveyed European companies, only 2 rely on a single department to set strategy — both use medical affairs. In fact, 30% of European companies ask four or more departments to assist in Phase IV strategy development.

One reason for such heavy Phase IV responsibility within medical affairs is due to the use of IIS as Phase IV studies. In addition, once pharmaceutical brand teams launch their products, companies often transition responsibilities away from the initial launch team. For example, many companies employ a lifecycle management team to oversee product activities after launch. This shift in responsibility allows the LCM team to prepare for the drug’s inevitable patent expiration. Phase IV studies play an important role in lifecycle management, especially when companies use study results to expand into new markets.

In much the same way, medical affairs teams take over responsibility for Phase IV studies after product launch. Company B, for example, shifts its post-marketing research operations away from its commercial teams to medical affairs. The company’s Phase IV study management organization is housed within medical affairs; however, the responsibility for setting strategy and executing the trials falls to each therapeutic area leader. Each therapeutic area also has medical directors who provide input on study strategy and execution, but the two responsibilities are not separate.

Company A’s medical affairs department sets the strategy for all Phase IV studies. For IIS, the medical affairs department works closely with each investigator to develop protocols that fit best with company strategy. The company’s medical affairs team is also responsible for approving the IIS and processing payments to investigators.

For company-sponsored studies, Company A’s vice president of medical affairs designed the main post-marketing research strategy with input from the company’s medical director and MSL director. However, the marketing or commercial operations group, in collaboration with medical affairs, often develops the strategy for a Phase IV study’s direction.

According to one interviewed executive at Company A, Phase IV studies are designed to support the brand franchises in each therapeutic area. In addition, the technical aspects of the study design, protocol, endpoints and analyses are all medical affairs’ responsibilities.

The following excerpt is taken from Chapter 2, “Phase IV Trial Timelines, Activities and Performance Metrics.” The chapter examines trial timelines and performance measurement, identifying areas that cause delays and providing solutions for trial acceleration. Benchmarking data for the EU and US are broken out by therapeutic area and by trial type. This excerpt discusses one of the greatest challenges — and areas for improvement — in Phase IV research: patient enrollment.

 

Patient Enrollment

Companies of all sizes struggle with patient enrollment. Surveyed companies offered a variety of reasons why patient recruitment and enrollment occupies such a significant amount of time. Companies face two major problems in recruiting patients. First, they have difficulty finding patients on the whole, whether the companies are looking for general practice patients or treatment-naïve patients. Second, even if there is a potential patient population to recruit, the competition for available patients is fierce.

Figures 2.31 to 2.38 show planned versus actual patient enrollment for IIS, comparative effectiveness, and registries and observational trials. IIS present the largest percentage deficit between planned and actual patient numbers, largely because IIS investigators tend not to have the experience and resources of the traditional investigators and centers used in Phase III trials. Registries and observational trials have the largest average difference between planned and actual patient enrollment numbers, but this is due to Company 20’s outlier data, in which it reported a 61% difference.

Lack of Patients

In Phase IV trials, many companies look outside the typical patient centers that would be used for Phase II and III studies. This is mainly to engage the more specialized patient populations sometimes required by post-marketing studies. And for companies that are accessing investigators and patients though the typical early-phase centers, many find it hard to locate qualified investigators and even harder to enroll the general practice patients in studies without enlisting the physician as an investigator. Companies will often provide additional training to investigators to encourage them to enroll, and in return, the company receives the benefit of enrolling that investigator’s patients in the post-marketing study.