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PHOTOGRAPHY: WESTEND61, PHOTOALTO/ERIC AUDRAS, GETTY IMAGES ILLUSTRATION: PAUL A. BELCI
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The growing need to establish a drug's safety and long-term efficacy in a given population has increased the number of late-phase
studies performed by the pharmaceutical industry over the past decade. The competitive drug market has driven companies toward
product differentiation and positioning, both of which may be determined through postmarketing studies. Strategic guidance
in areas such as reimbursement, franchise development, and marketing is provided through late-phase studies.1Late-phase trials are postmarketing studies and classified as Phase IIIb or IV. The term Phase IIIb is used by the industry
to describe additional therapeutic exploratory and confirmatory studies conducted after the primary regulatory dossier has
been submitted by the manufacturer. They are typically conducted on marketed drugs to look for a new indication. Ziprasidone
hydrochloride (Geodon), a commonly used antipsychotic introduced to the market for the treatment of schizophrenia in February
2001, received approval for treatment of bipolar mania in August 2004 as a result of Phase IIIb research.2
Phase IV studies are typically conducted to capture physician prescription patterns, evaluate adherence to treatment guidelines,
and conduct safety surveillance after the approval of a drug. Phase IV postmarketing research has evolved into patient registries,
risk management programs, postmarketing surveillance programs, observational studies, disease management programs, and care
quality improvement initiatives.3
Figure 1. Some of the main factors that lead to treatment ineffectiveness.
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The Phase IV research environment is largely driven by the changing regulatory environment, increasing safety concerns of
new medicines, and the need for real-world data on the marketed drugs' safety and efficacy.4 The association between long-term combination Hormone Replacement Therapy use and a heightened risk of breast cancer was
discovered during a Phase IV trial partially funded by Wyeth and conducted by the National Institutes of Health.
Patient power
Decision-making by health care professionals in the United States is primarily based on patient visits, is highly decentralized,
and driven by professional autonomy to a large extent.5 The prevailing model of health care delivery is complicated, comprised of layers of processes and handoffs that result in
slow and expensive health care. The system often fails to consider the importance of tailoring care based on patients' needs.
While health care delivery needs to be timely and safe, the overall effectiveness of treatment can be optimized through patient-level
feedback.
Some of the main causes for treatment ineffectiveness have been described in Figure 1. Patient noncompliance, driven in part
by lowered treatment satisfaction, has emerged as one of the leading causes for treatment inefficacy. High patient noncompliance
leads to annual economic losses of up to $100 billion in the United States. Studies have shown that noncompliance causes 125,000
U.S. deaths annually, and hospital costs due to noncompliance have been estimated to be $8.5 billion annually.6
Since the 1990s, studies have shown that systematic attention to patient feedback on health care outcomes and behavioral change
lead to improved treatment outcomes.7 According to an IBM publication on health care in the 21st century,8 a patient-centric approach would ensure an improvement in health; a reduction in costs and premiums by payers; improvements
in the efficiency, quality, and safety of care; and a reduction of the financial burden in the industry.
Outcomes that matter to patients following treatment can be gauged most accurately using patient-reported outcomes (PRO) measures.
The term PROs has evolved to include any endpoint derived from patient reports, whether collected in the clinic, using a diary
or by other means, including single-item outcome measures, event logs, symptom reports or longer questionnaires. PROs are
typically used to measure health-related quality of life (HRQoL), health status, symptoms, adherence, and treatment satisfaction.9 The selection of appropriate PRO instruments depends on the study design, nature of the intervention, and the target population.
Results from psychometrically validated PRO measures can help us learn about overall patient treatment satisfaction, treatment
effectiveness, and the impact of the drug on patients' day-to-day lives (see Figure 2). Physicians can gain useful feedback
on prescribed treatments and could alter their course of treatment to improve the care delivered.
