Pharmacoeconomic trials

A related issue in pharmacoeconomics trials is the generalizability of the health care delivery system of the patients in the study. A pharmacoeco-nomic study conducted through health a maintenance organization using its members as subjects may observe less referrals to specialist physicians than would the same clinical study in a different practice setting. This effect may be even more pronounced in multinational clinical trials, in which health care systems, physician education, and patients expectations for treatment differ by country. 

To obtain reimbursement and formulary acceptance as health-care dollars become scarcer, the sponsor at launch or soon after should be able to demonstrate cost-effectiveness, superiority, convenience, and patient satisfaction, usually through data from Phase IV pharmacoeconomic trials (see also Chapter 19). 

The validity of pharmacoeconomic data is invariably diminished by two important factors a failure to account for all direct and indirect cost outcomes, and the difficulty of assigning costs to human experiences. In schizophrenia, validity is further reduced by the near-impossibility of conducting trials over several years, or even decades, so as to approach the reality of what is usually a lifelong illness. Given these observations, it would be imprudent to act on the minutiae of data generated in even the best-conducted trials, but it may well be appropriate to draw broad conclusions. 

Pharmacoeconomic evaluations of olanzapine are dominated by data generated from a single company-sponsored clinical trial (Tollefson et al, 1997) and its follow-up. The large number of participants in the trial and its international namre have afforded the opportunity for separate analyses according to country or continent. Whether or not this is a valid approach is debatable. 

Hamilton SH, Revicki DA, Edgell ET, et al (1999). Clinical and economic outcomes of olanzapine compared with haloperidol for schizophrenia results from a randomised clinical trial. Pharmacoeconomics 15, 469—80. 

Forder et al, 1996 Hylan et al, 1997) have described the breadth of health utilization that needs to be included for pharmacoeconomic studies. Nevertheless, attempts are still being made to limit the broad perspective that is required. Hotopf et al (1996) suggested that data for pharmacoeconomic evaluations should be limited to three sources randomized, controlled trials meta-analyses ... 

The pharmacoeconomics of the anxiety disorders has received litde attention. In the past drug costs were largely incurred by use of benzodiazepines, most of which are available in generic forms and are cheap. They are effective and acceptable in the short term. Long-term use is associated with the risk of physical dependence, with an adverse risk—benefit ratio and high cost terms to facilitate withdrawal. There is now a trend towards the use of antidepressants in the anxiety disorders. Clinical experience has been followed by formal trial evaluation. 

In recent years in some developed countries, the requisite of presenting economic evaluation (that is, pharmacoeconomic) studies of new dmgs has been introduced alongside the existing one of clinical trials. These studies have to provide proof of their efficiency (or cost-effectiveness) as a condition for the public financing of the new product. These studies improve information and market transparency and may help to make competition keener, but like the earlier requirements regarding effectiveness and safety, they constitute an additional cost factor and as such raise further barriers to entry. 

Therapeutic use (Phase III/IV) Refine understanding of benefit/risk relationship in general or special populations and/or environment Identity less common adverse reactions Refine dosing recommendation Comparative effectiveness studies Studies of mortality/morbidity outcomes Studies of additional endpoints Large simple trials Pharmacoeconomic studies... 

Refine dosing recommendations Studies of additional endpoints Large simple trials Pharmacoeconomic studies... 

Within the last 20 years or so, three major features of controlled clinical trials, in particular, have permitted significant advances in deciding whether treatments are of value or not randomisation, systematic review and metaanalysis, and the concept of the large-scale, simple (to understand and conduct) randomised trial in areas where only moderate benefits can be expected.All of these elements are likely to underpin future trials for purposes of regulation, pharmacoeconomics and healthcare policy. Yet there is no room for complacency or allowing standards to slip. Systematic reviews of some... 

Mauskopf J, Schulman K, BeU L, et al. A strategy for collecting pharmacoeconomic data during Phase 9 II/III clinical trials. PharmacoEconomics 1996 264-77. 

We have already addressed some of the general issues in the design and interpretation of pharmacoeconomic studies. Yet, prospective pharmacoeconomic studies, especially within phase III clinical trials, are often our only opportunity to collect and analyze information on new therapeutic products before decisions are made concerning reimbursement and formulary inclusion for these agents. We now address issues that arise in the design of these studies. 

Mauskopf J, Schuknan K, Bell L, Glick H. A skategy for collecting pharmacoeconomic data during phase lEIII clinical trials. Pharmacoeconomics 1996 9 264-77. 

This is the infrastructure that makes it possible for the clinical pharmacologist is to advise government and to provide leadership in drug policy, clinical trials, ethics of clinical studies, pharmacoeconomics, pharmacoepidemiology, drug regulation, the scientific basis of drug development, traditional medicines, and complementary medicines. 

Surveillance for safety and efficacy further formal therapeutic trials, especially comparisons with other drugs, marketing studies and pharmacoeconomic studies. 

Not all clinical trials, especially large, multisite, multinational phase III studies and phase IV postmarketing surveillance, pharmacoeconomic, and quality-of-life studies, can be conducted at a CSO facility. These types of studies, and many phase II efficacy studies, are conducted in research- or university-based hospitals or other investigational sites where a sufficient patient population with the disease or disorder to be tested is available. A number of CSOs offer services to support clinical trial studies that are implemented at one or more clinical trial sites. These services can be broken down into relatively broad categories, which are summarized later. 

Post-marketing surveillance studies, pharmacoeconomic studies, non-interventional trials, clinical audit programmes and the like, which have been commissioned, undertaken or provided by companies, must never be promotional in nature and must be conducted primarily with a scientific or educational purpose. This clause does not preclude the use of the data generated from such studies to support claims in promotion. 

Both the quantity and the types of data able to be collected will be affected by the nature of the clinical study patients may be inpatients or outpatients, and this in turn will govern the nature of pharmacoeconomic data that can be recorded. It is also important whether a clinical trial is intended as a pivotal trial for registration or not if a study is pivotal, then a clinical efficacy measure will have to be the primary end point. Pharmacoeconomic parameters can still be incorporated into such a study as secondary end points, and still provide valuable information. If, on the other hand, the clinical research addresses a health system delivery issue, then the pharmacoeconomic end points may well be primary, and the study design need not be constrained by FDA-mandated requirements for the double-blind, placebo-controlled aspects of proof of efficacy. 

Table 23.3 Points to consider incorporating pharmacoeconomic measures in clinical trials...

To plan and implement successful launch campaigns, the pharmaceutical industry will increasingly need to meet managed care s need for practical pharmacoeconomic and outcomes data to assist in formulary decision-making processes. Therefore, in the future, the pharmaceutical industry may conduct prelaunch clinical trials in MCOs... 

Promoting the participation of pharmacists in clinical trials and pharmacoeconomic studies. 

---