Optimizing the Clinical Trial Process: Strategies to Reduce Costs and Increase Quality

SUMMARY

INTRODUCTION

Expenditure on research and development by the pharmaceutical industry is increasing worldwide and is currently estimated to be over $45 billion ayear. Within the R&D process, clinical trials form the largest single cost center for new drug development. In order to maintain profitability,companies need to take measures to improve the efficiency and effectiveness of the clinical trial process.

SCOPE OF THE REPORT

• Quantifies the expenditure on R&D by the pharmaceutical industry and assesses the impact of increasing R&D spend on total sales
• Determines the monetary and time costs of the clinical trial process and identifies the critical drivers of these costs
• Presents the elements of effective clinical trial design together with extensive case studies
• Evaluates the cost of delays in subject and investigator recruitment and offers strategies for improvement

REPORT HIGHLIGHTS

Pharmaceutical industry expenditure on R&D is increasing at a rate greater than the number of innovative drugs generated through suchinvestment. Considering the dry spell in the R&D pipeline, the reduction of drug development costs has become imperative.

The responsibility of clinical trial design should be shared across disciplines within a pharmaceutical company organization. Research, marketing,clinical affairs and competitive intelligence departments should all be included.

To ensure regulatory approval for a drug candidate, pharmaceutical companies need to increase close contact with regulatory bodies throughout theclinical trial process, particularly during the design of phase III trials.

KEY REASONS TO BUY THIS REPORT

• Understand the magnitude and scope of the current R&D productivity challenge
• Identify the critical drivers of the monetary and time costs in clinical trials
• Adjust your investigator and patient recruitment strategies to reduce the costs of related delays

TABLE OF CONTENTS

EXECUTIVE SUMMARY

• Datamonitor insight into the optimization of the clinical trial process
• Pharmaceutical industry expenditure on R&D is increasing at a rate greater than the number of innovative drugs generated through such investment. Considering the dry spell in the R&D pipeline, the reduction of drug development costs has become imperative
• The responsibility of clinical trial design should be shared across disciplines within a pharmaceutical company organization. Research, marketing, clinical affairs and competitive intelligence departments should all be included
• To ensure regulatory approval for a drug candidate, pharmaceutical companies need to increase close contact with regulatory bodies throughout the clinical trial process, particularly during the design of phase III trials
• To recruit subjects for clinical trials successfully and efficiently, pharmaceutical companies should focus on utilizing those physicians that have relationships with broad patient populations as recruiters

CHAPTER 1

• Key findings
• Declining R&D productivity
• Overall R&D spend is growing
• US versus non-US R&D spend
• R&D spend versus total sales
• Dry spell in the pharmaceutical industry pipeline
• Improved efficiency of the FDA
• R&D spend per drug approval
• Direct calculation of R&D spend per drug approval
• Research on the growing costs of new drug development
• Escalating costs of clinical trials
• Proportion of total R&D spend attributable to clinical trials
• More time needed to complete clinical trials
• Differences in the cost and length of trials by therapy area
• Drivers of cost
• Increasing complexity of trials
• Changes in the regulatory environment
• Global trials
• Delays in subject and investigator recruitment
• Inefficient data collection and management
• Product recalls
• Defining 'quality' in clinical trials
• Clinical trials as a science-driven process
• Clinical trials as a marketing-driven process
• The 'optimized' clinical trial
• Steps of the clinical trial process
• The opportunity to optimize the clinical trial process

CHAPTER 2

• Key findings
• The importance of clinical trial design
• Impact of design on quality and cost
• Clinical trial shortfalls
• AstraZeneca's AZD3582
• Merck's GABA-A a2/a3 Compound
• Abbott's Atrasentan
• Sanofi's Dronedarone
• Objectives of clinical trial design
• Short-term objectives of trial design
• Medium-term objectives of trial design
• Long-term objectives of trial design
• The importance of stop-go decision-making
• Elements of clinical trial design
• Meeting the requirements for regulatory approval
• High-profile drug rejections by the FDA
• Increasingly rigorous FDA approval process
• FDA poised to help speed drug approval
• The importance of communication with regulatory agencies
• Marketing to physicians and patients
• What physicians require from product marketing
• Pre-approval comparator drug studies
• Post-approval comparator drug studies
• Patient requirements
• Marketplace to penetrate
• Biogen's Amevive to face competition
• Pharmacoeconomic considerations
• Boehringer Ingelheim's Viramune and its pharmacoeconomic differentiation
• The responsibility of clinical trial design

CHAPTER 3

• Key findings
• The evolving challenge of clinical trial recruitment
• The cost of delays in clinical trial recruitment
• The current recruitment process
• Overview
• Recruitment strategies today
• Developing relationships with investigators and patients
• Targeting physicians
• Physician investigator requirements
• Strategy to recruit physicians
• The desired role of physician investigators
• Recruiting the right patients and then keeping them
• Attraction - getting plenty of appropriate patients
• eRecruitment
• Conversion - ensuring the right patient mix
• Retention - keeping patients until trial's end
• The role of pharmacogenomics in screening
• Outlook

CHAPTER 4

• Key findings
• Data capture, management and analysis
• Market overview
• Size of the eDC and management markets
• Electronic data capture
• Inefficiency of paper-based data collection
• Physician investigator use
• Barriers
• Security
• Lack of standards
• Cost
• Electronic patient diaries
• Patient diaries: paper versus electronic
• Applications of ePDs
• The current market for ePDs
• Best practices in the application of ePDs
• Vendor market
• Outlook for ePDs
• ePD going forward
• Legal ramifications
• US regulatory issues
• European regulatory issues
• Submission to regulatory authority
• eSubmissions
• Regulations for electronic submissions
• Addressing the challenge of products with a global market
• Common Technical Document guideline

CHAPTER 5

• Supplementary data
• 21 Code of Federal Regulations Part 11
• Subpart A-General Provisions
• Subpart B-Electronic Records
• Subpart C-Electronic Signatures
• Research methodology
• References
• Future readings
• Relevant links
• SPP writing team
• Datamonitor's Healthcare Strategy Business Unit
• Nick Bennett, Strategy Lead Analyst
• How to contact experts in your industry

LIST OF TABLES

• Table 1: R&D expenditure within the US and abroad by PhRMA member companies
• Table 2: NDAs and NMEs approved (1986-2002)
• Table 3: Direct calculation of R&D spend per NME approved (1990-2002) 34
• Table 4: US R&D spend by function for PhRMA member companies (1998-2000)
• Table 5: US R&D spend by function for PhRMA member companies in 2001
• Table 6: Drug development times from synthesis to approval in years (1960-1999)
• Table 7: Summary of possible cost and time savings using eRecruitment
• Table 8: The 22 websites reviewed by the OIG
• Table 9: The clear presentation of trial-specific information on clinical trial websites is a key success factor
• Table 10: The largest number of data items collected on a single day basis is in Phase III and IV trials
• Table 11: Various costs associated with the paper-based collection and management of clinical trial data
• Table 12: The utilization of electronic NDA submissions is increasing exponentially

LIST OF FIGURES

• Figure 1: NME approvals versus US R&D spend (1980-2002)
• Figure 2: The New Drug Development Process 9
• Figure 3: The productivity crisis in R&D
• Figure 4: Domestic R&D expenditures in the European Union (1990-2000)
• Figure 5: The total pharmaceutical R&D spend more than doubled in the US between 1995 and 2000
• Figure 6: R&D spend as a percentage of sales, PhRMA member companies (1980-2002)
• Figure 7: NDA and NME approvals (1986-2002)
• Figure 8: NME approvals versus US R&D spend (1980-2002)
• Figure 9: Direct calculation of R&D spend per NME approval (1990-2002)
• Figure 10: The cost of developing a new drug has increased greatly since 1975
• Figure 11: The greatest level of expenditure during the clinical evaluation function is found in phase III
• Figure 12: US R&D spend on clinical trials by PhRMA member companies (1998-2001)
• Figure 13: The clinical phase of the drug development time has grown in each decade
• Figure 14: Indexed number of medical procedures per patient in clinical trials: Phases I-III (1992-2000)
• Figure 15: The New Drug Development Process
• Figure 16: Seventy-eight per cent of clinical trials missed their scheduled enrolment deadlines
• Figure 17: The Internet penetration in the surveyed countries is high, indicating the potential of online resources as an effective communication channel
• Figure 18: More than half of the physicians in all surveyed countries either currently use or would like to use the Internet to access information on clinical trials
• Figure 19: In the clinical trial process, pharmaceutical company sponsors should take measures to attract, convert and retain patients until completion of the trial
• Figure 20: Among the countries surveyed, the US has the largest proportion of consumers looking for health-related information
• Figure 21: Health information websites are the most popular online resource among consumers looking for health-related content in the US and all European countries surveyed
• Figure 22: Internet-enabled electronic data capture and management-a benefit for all clinical trials
• Figure 23: Electronic patient diaries have the potential to resolve many of the problems associated with paper-based diaries
• Figure 24: Datamonitor forecasts that the proportion of patient diaries that are electronic-based will increase as their use moves out of the pilot phase
• Figure 25: The appropriate form of electronic patient diary is dependent on the complexity of the self-report data and frequency with which it must be collected