Unlocking the power of pharmacovigilance* An adaptive approach to an evolving drug safety environment PricewaterhouseCoopers’ Health Research Institute Contents Executive summary 01 Background 02 The challenge to the pharmaceutical industry 02 Increased media scrutiny 02 Greater regulatory and legislative scrutiny 04 Investment in pharmacovigilance 05 The reactive nature of pharmacovigilance 06 Unlocking the power of pharmacovigilance 07 Organizational alignment 07 Operations management 07 Data management 08 Risk management 10 The three strategies of effective pharmacovigilance 11 Strategy 1: Align and clarify roles, responsibilities, and communications 12 Strategy 2: Standardize pharmacovigilance processes and data management 14 Strategy 3: Implement proactive risk minimization 20 Conclusion 23 Endnotes 24 Glossary 25 Executive summary The idea that controlled clinical incapable of addressing shifts in 2. Standardize pharmacovigilance trials can establish product safety public expectations and regulatory processes and data management and effectiveness is a core principle and media scrutiny. This reality has • Align operational activities across of the pharmaceutical industry. revealed issues in the four areas departments and across sites Neither the clinical trials process involved in patient safety operations: • Implement process-driven standard nor the approval procedures of the organizational alignment, operations operating procedures, work U.S. Food and Drug Administration management, data management, and instructions, and training materials (FDA), however, can provide a perfect risk management. • Integrate safety data through guarantee of safety for all potential data and system interoperability consumers under all circumstances. When appropriately aligned and standards Despite this fact, there are viable supported, these areas can work • Implement workflow management solutions that pharmaceutical together to enable a flexible, technology to ensure appropriate companies can implement to support adaptable, and proactive system transparency and accessibility of pharmacovigilance—the systematic for addressing patient safety safety information detection, assessment, understanding issues. Companies can unlock the • Select a vendor that best matches and prevention of adverse drug power of their pharmacovigilance the pharmacovigilance operating reactions. When built into existing activities by creating an operational model, business process and research and development practices, framework that supports the key vendor/system selection criteria pharmacovigilance activities can patient safety infrastructures. The enhance patient safety while reducing following are recommendations for 3. Implement proactive risk or even preventing costly safety- companies developing an adaptive minimization related withdrawals. pharmacovigilance framework: • Develop risk management action plans based on pre-established risk Currently, however, pharmaceutical 1. Align and clarify roles, scoring mitigation processes executives face a number of challenges responsibilities, and communications • Implement data mining techniques in the area of pharmacovigilance. In • Develop an objective, data-driven, to bolster safety analytics, reporting, the four decades from the thalidomide team-based approach to risk and investigation tragedy to the recent concerns monitoring and evaluation • Incorporate continuous improvement about Vioxx, companies have used • Implement well-defined decision- activities and standardized risk pharmacovigilance methods designed making models, escalation communication plans to identify rare, easily identified safety processes, and communication • Create a dashboard that summarizes problems At the same time, we have channels and promotes timely awareness seen the growth of a fragmented • Determine the pharmacovigilance of safety risks across the portfolio healthcare system that has lacked workload and sufficiently resource and timely execution of safety risk a unifying infrastructure. As a result, the required effort minimization activities this system operates primarily in • Designate a pharmacovigilance reaction to rather than in anticipation operating model and business of major pharmaceutical safety events. process owner As drug consumption has increased • Ensure that appropriate process and and the public has grown to expect organizational checks and balances greater drug safety, the traditional are in place to limit bias and manage reactive approach has proven largely regulatory risk PricewaterhouseCoopers’ Health Research Institute | 1 Background The challenge to the Exhibit 1: Frequency analysis of ethical issues pharmaceutical industry Ethical issue Number of references Drug safety 114 A chief problem that pharmaceutical Drug prices 54 companies face in the area of Cinical study design & sponsorship 30 pharmacovigilance is the possibility Data disclosure—clinical and manufacturing 26 that a medicine may be taken in Marketing sales and incentives 14 a manner for which it was neither Reimportation/importation 13 New drug/treatment research 13 intended nor clinically tested. Developing countries 12 This can happen for a number of Issues related to vaccines 12 reasons: the number of participants NIH ethics rule 9 in the average clinical trial is dwarfed Righ tot life/contraception 9 by the thousands or even millions of DTC advertising 8 biologically unique patients who may Generic drugs 3 Medicare/Medicaid 3 take a marketed treatment; medicines Other 25 can be taken in combination with other therapies with which they have not Source: “Front Page Pharma,” by Stephen J. Porth and George P. Sillup, Pharmaceutical Executive, been clinically tested; and medicines February 1, 2006. may be prescribed for an indication different from the one for which they were approved. All of these factors, Exhibit 2: Prescription drug adverse event report growth, U.S., since 1995 including preexisting conditions, may increase the odds that serious adverse 23% events absent in clinical trials might easily occur postmarket. 16% 15% 13% 13% 14% Neither these odds nor the risks 12% 11% average 7% they represent are well understood annual by consumers, the result being that growth rate a spate of safety-related product withdrawals has hastened the recent -4% steep decline of public confidence in the ability of pharmaceutical 1996 1997 1998 1999 2000 2001 2002 2003 2004 companies and regulators to ensure Source: “CDER 2004 Report to the Nation: Improving Public Health Through Human Drugs,” Center safety. for Drug Evaluation and Research. August 22, 2005. Increased media scrutiny Growing public concern over drug safety also has spurred the media to focus on this issue. Drug safety was the top issue in Pharmaceutical Executive’s Annual Media Audit 2005, with drug safety and development issues dominating more than half of the print media coverage (Exhibit 1). Heightened media and public 2 | Unlocking the power of pharmacovigilance awareness has combined with Exhibit 3: The downward safety spiral greater scrutiny by regulators and elected officials to create a rapidly evolving—and potentially dangerous—environment for pharmaceutical companies. One reason for such media scrutiny Upstream risks is the release of reports from the FDA and the World Health Organization’s Vigibase (a global adverse drug reaction database) of significant increases in the number of adverse events reported in recent years. The FDA, for example, shows an average growth rate of 12% annually in adverse event reports to the agency from 1995 through 2004 (Exhibit 2). The causes and implications of the increase are the subjects of much debate. Despite increases in adverse Business/financial Safety risks event reports, safety-based drug impacts withdrawals in the U.S. have remained essentially flat, at about 3 per 100 New Chemical Entity approvals for the past 35 years.1 The public may view the increase in reported adverse events negatively, but the growing number of reports may result, in part, from increased awareness in the medical community and the sheer increase in drug consumption. The industry could benefit greatly if the public better understood these factors and their impact on pharmacovigilance. The impacts of safety issues are not limited to perception alone. Safety issues can lead to regulatory fines, litigation costs, reduced market share, diminished brand equity, and decreased shareholder value. Such impacts may affect a company’s ability to finance safety initiatives and thereby induce a downward spiral of further safety-related strategic and operational issues (see Exhibit 3). PricewaterhouseCoopers’ Health Research Institute | 3 Consumers do not hold industry solely “The public perception that every Partly in response to the GAO’s responsible for safety issues but blame problem can be solved by a pill has report, the FDA created the position government as well. A 2005 consumer to change,” said Raymond L. Woosley, of associate center director for safety survey conducted by the Henry J. M.D., Ph.D., president of the Critical policy and communication within Kaiser Family Foundation reported Path Institute. “Drugs are foreign the Center for Drug Evaluation and that 77% of respondents were “very” chemicals, and while they have Research to oversee drug safety or “somewhat” confident in the ability beneficial effects, they also have side issues and policies.5 of the FDA to ensure that prescription effects. The public must understand drugs are safe. Even so, 22% were that because