What are late-phase clinical studies and why are they important?

Late-stage clinical studies are postmarketing trials classified as Phase IIIb and Phase IV that are conducted to establish a drug’s long-term safety and efficacy following regulatory approval, and to provide product differentiation and positioning in the competitive drug market place.

As with Phase II and Phase III studies, patients represent valuable data, therefore retention of patients, so that they are not lost to follow-up (LTFU) is equally important in later phase studies to assure appropriate data collection and dissemination of results.

Is there a difference between Phase IIIb and Phase IV studies?

Yes.  Phase IIIb are typically conducted to provide head-to head comparison data, confirmation of earlier results prior to product approval and/or to gain approval of the drug for an additional therapeutic indication.  Phase IV studies are conducted for several postmarketing objectives such as pharmacovigilance, patient registries, disease and risk management, and patient reported outcome.

What are the implications of patient reported outcomes (PRO)?

Studies have shown that attention to patient feedback on healthcare outcomes and patient behavior change can lead to improved treatment adherence and outcomes.¹ Applying such results to all early and late phase clinical studies, can help retain patients so that they are not LTFU.

What do PRO measure?

PRO measures are used to assess several factors such as health-related quality of life (HRQOL), treatment satisfaction, and disease symptoms and include and use endpoint derived from patient reports collected from several sources such as investigator sites, patient diaries, questionnaires, etc.²

What are some examples of PRO outcomes?

PRO endpoints in late-phase trial are used to gain patients’ perspectives in several areas such as support of secondary indications for an approved product label; revised guideline treatment recommendations and addition of an agent or tier advancement in manage care formulary.³

Notably, regardless of the clinical development and postmarketing programs designed for the lifecycle of a drug, valuable patient efficacy and safety data along with their treatment perspectives are critical for the long-term longevity of a product. Therefore patient retention efforts including a process to find those LTFU are essential to insure such success.

What is OmniTrace and how can it assist drug manufacturers in finding early and late stage clinical trial patients LTFU?

Omnitrace is a people locate company that has been in operation for 8 years.  Omnitrace has a stellar record of success in locating thousands of people worldwide, servicing several sectors including the pharmaceutical/biotechnological industry in finding clinical trial patient dropouts and those LTFU.  As mentioned, as every participant in clinical research is a valuable source of safety information, locating patients Lost To Follow-Up (LTFU) is critical to maintaining a robust risk management system.

References

1. Institute of Medicine, Crossing the Quality Chasm-A New Health System for the 21^st Century, 1^st Edition National Academies Press, Washington, DC, 2001

2. R.J. Willke, L.B. Burke, P. Erickson, “Measuring Treatment Impact: A Review of Patient-Reported Outcomes and Other Efficacy Endpoints in Approved Product Labels,” Controlled Clinical Trials, 25 (6) 535-552 (2004).

3. E.P. Rock, D.L. Kennedy, M.H. Furness et al., “Patient-Reported Outcomes Supporting Anticancer Product Approvals,” Journal of Clinical Oncology, 25 (32) 5094-5099 (2007).

With an overall goal in protecting public health, the objective of pharmacovigilance (PV) is to promote the safe clinical use of medicines and prevent adverse drug reactions from clinical investigation throughout post-marketing of a drug.  While there are multitudes of factors that affect a PV program, the focus of this article is risk management and the associated value of patients’ participating in clinical research, as they are a major resource to clinical drug development and represent important safety information during the clinical trial period and beyond.

What is pharmacovigilance (PV) and how does it relate to clinical research?

PV is an integrated risk management approach/system developed in efforts to assure drug safety from the clinical research stage through post marketing of a drug.1

What are the ramifications of insufficient risk management/PV systems?

The three main consequences are drug failures, drug withdrawals, and new regulations.  In the past decade a significant number of high-profile brands have struggled with safety concerns, either causing such drugs to be withdrawn from the market1 (e.g., Rezulin,Vioxx, Bextra), or those alerting U.S. lawmakers to enforce stricter laws and regulations.  A current example is the FDA recommendations that all antihyperglycemia agents under clinical development demonstrate lack of cardiovascular adversities the basis of which was fueled by concerns raised about the cardiovascular safety of drugs in this field, especially the thiazolidinediones (TZDs), including rosiglitazone (Avandia, GlaxoSmithKline).2

What key issues are involved with drug safety that a successful risk management/PV program can enhance?

*  Risk management from clinical trial participation through post marketing
*  Safety surveillance to detect adverse signals
*  The establishment and continuous monitoring of a drug’s benefit-risk relationship

How can the three key issues be managed more successfully?

One key factor that can favorably affect success is establishing effective patient retention processes from the time of participation in a clinical study throughout the postmarketing period of a drug; patients drop outs or those lost to follow-up (LTFU) represent valuable safety information long-term.

What percentage of patients’ drop out of clinical research or are LTFU that  hinder risk management?

There are various statistics reported depending on the investigational drug being studied. Centerwatch3 in past surveys has reported up to a 30% drop out rate overall and a study investigating arthritis medicine in osteoarthritis patients reported a 45% drop out with 54% of those LTFU. 4

Who is Omnitrace and how can it assist drug manufacturers in risk management/PV approaches?

Omnitrace is a people locate company that has been in operation for 16 years.  Omnitrace has a stellar record of success in locating tens of thousands of people world-wide, servicing several sectors including the pharmaceutical/biotechnological industry in finding clinical trial patients and those who dropout and become LTFU.   As mentioned, as every participant in clinical research is a valuable source of safety information, locating patients LTFU is critical to maintaining a robust risk management system.

What have we learned from drug manufactures that have established an effective PV process?

An integrated approach that takes into account the key stages of drug development including preclinical, clinical and postmarketing is critical.  The sum of several factors are required for success: Prepahase safety considerations + PV safety strategy + clinical trial safety including surveillance + risk management planning, plans, and strategy + postmarketing surveillance + signal detection of adverse events.5

As demonstrated, multifaceted issues affect risk management and PV systems. While the equation of success can be overwhelming, a common dynamic that exists throughout the process is the research participants as they represent important safety information during the clinical trial period and beyond.  Integrating an effective patient retention program so patients don’t drop out or are LTFU will assist in facilitating a successful PV strategy.

References
1. Maennl, U. Pharmacovigilance: A Company-Wide Challenge. (2008) Accessed http://appliedclinicaltrialsonline
2. Food and Drug Administration. FDA announces new recommendations on evaluating cardiovascular risk in drugs intended to treat type 2 diabetes. December 17, 2008. Available at: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01928.html
3. Available at http://www.centerwatch.com
4. Wider, F., Barrett, J. The association between medication usage and dropout status among participants of an exercise study for people with osteoarthritis. Physical Therapy (2005) 85; 142-149)
5. P.C. Waller and S.J.W. Evans, “A Model for the Future Conduct of Pharmacovigilance,” Pharmacoepidemiology and Drug Safety, 12, 17-29 (2003).

Please contact our CEO David Betz at 888-965-6696, and he will answer any immediate questions you have and provide you information about our OmniTrace lost to follow-up patient search services.  You can also email David at:  dave@omnitrace.com.

THE CONTENT ON OUR OMNITRACE OWNED WEBSITES IS MERELY GENERAL INFORMATION OBTAINED BY ORDINARY PEOPLE AND NOT LEGAL ADVICE.  ONLY A QUALIFIED LAWYER CAN GIVE LEGAL ADVICE.  WE ARE NOT LAWYERS.