Patient population trials

First, the most recent (October, 2000) revision of the Declaration of Helsinki (World Medical Association, 2000) calls for discontinuing the use of placebo controlled trials in patients. While this is not currently binding on U.S. trials (FDA has specifically said that they will not mirror this as a requirement), and is intended to protect the health of participating patient subjects by precluding having some denied existing efficacious treatments (which would be the effect in most—but not all—cases), it will also likely cause the numbers of subjects required in a trial to increase. This will further stretch the economic aspects of limitations on the power of trials to assess potential drug safety in what will be the intended patient population. Trials are already very expensive each additional subject enrolled costs 15,000 or more in a Phase 11 or 111 trial. 

A key element in planning and conducting clinical trials is to ensure that they have scientific validity and objectivity. This is particularly relevant with respect to Phase II and III studies, where it is desired to demonstrate a positive benefit to risk outcome. Responses to a drug among a patient population are rarely homogeneous and clear-cut. Thus, sound statistical principles must be applied in order to be able to distinguish significant effects from random events. 

DeVincenzo et al. 2008). Phase n clinical trials in naturally infected RSV patients were initiated in April 2008. ALN-RSVOl is expected to advance into the pediatric patient population by the second half of 2008. 

Certain patient populations require special considerations due to their altered metabolism, unique volume of distribution, or increased risk for side effects.43 Although many of these patients are excluded from clinical trials in SE, the standard algorithm for SE still applies for these patients in terms of immediate care, assessment, and drugs (see Table 28-2). 

There are several areas of study that will help you understand the research topic. As a first step you will want to read the clinical protocol. The protocol describes the device or medication to be used, the patient populations under study, the statistical plan of the clinical trial, and the details of the disease state. If you want to understand the disease state or indication further, you may want to seek out a clinical investigator of the clinical trial or do some further reading about the disease. Understanding the patient population is a good way to understand the data that you will see and whether there is reason for concern when viewing the data. For example, if you were studying a medication to reduce hypertension, you would not be as worried if patient blood pressure data were elevated at baseline. You would expect to see this because you understand that hypertensive patients have high blood pressure. 

Finally, a major question in SERM development is whether the new compounds will behave like estrogens with respect to cardiovascular events, which would be a worthless property given the results of the WHI trial (Writing Group for the Women s Health Initiative Investigators 2002 Women s Health Initiative Steering Committee 2004). This is a complex issue that will depend on the unique profile of action of the new SERM on the different components of the atherosclerosis process and the patient population and study design and conduct that is implemented. 

Therapeutic exploratory (Phase lb/II) Explore use for the targeted indication Estimate dosage for subsequent studies Provide basis for confirmatory study design, endpoints, methodologies Earliest trials of relatively short duration in well-defined narrow patient populations, using surrogate or pharmacological endpoints or clinical measures Dose-response exploration studies... 

The type of patient population and the desired format of the test to be used in a clinical trial also influence the particular scale(s) chosen. 

Too median Most premarketing trials exclude patient populations such as pediatric, geriatric, lactating, and pregnant patients. 

Phase Ilia. Trials conducted after efficacy of the medicine is demonstrated, but prior to regulatory submission of a New Drug Application (NDA) or other dossier. These clinical trials are conducted in patient populations for which the medicine is eventually intended. Phase Ilia clinical trials generate additional data... 

The principal role of the CRO is to contribute to the enhancement of the financial performance of its customers (Table 21.1). Improvement in the efficiency of their clients product development activities provides benefits to regulators, physicians and their patients. These include reduced cycle time, availability of external capacity, increased quality of trial management, and higher quality clinical data, all of which can result in lower labor costs. In late stage peri-approval trials, CROs may also play a role in developing safety profiles in large patient populations that are exposed to a new product after it is approved for manufacture and sale. Such trials can also assist the revenue growth of a new product. 

IT advances have already had a major beneficial impact on medical product development and registration. Some of the major advances in this area are electronic filing of applications for regulatory approval, RCDC, and clinical trial management software. The application of software to the analysis of the genetic profile of large patient populations is an example of the powerful intersection of pharmacogenomics and IT. 

There are several inherent weaknesses in observational trials, hi controlled clinical trials, every effort is made to select patient populations in a way that excludes as many variables as possible between the placebo- and drug-treated groups, leaving drug treatment as the only variable. This ideal cannot be strictly realized in practice but experienced investigators come pretty close. Beyond that, controlled clinical trials state upfront what the primary and secondary endpoints... 

Phase III Extended large-scale trials to obtain additional evidence of efficacy and safety, and definition of adverse effects. Humans exposed several hundred to several thousand Phase IV Post-marketing surveillance occurs after the chnical trials programme is complete. It is used to collect adverse event data from a large patient population. Humans exposed 10 000+... 

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