Variability, individual patients

That done, the next step is not to do inference tests but, instead to inspect the raw data listings organized by variable, groups of variables, individual patients, and frequency distributions. Note observations or sets of data that are outliers by any large measure and track them as far back as necessary (all the way to the original case report forms if indicated). If the anomaly appears there, seek confirmation from the clinicians. The smaller the sample size, the more important this diligence becomes. 

Figure 27.3 Once the data are transformed into CDISC standards and integrated with a drug safety analysis system, the data can be easily analyzed. In this figure we show a sample screen from WebSDM a drug safety analysis system being evaluated by the FDA. This screen allows the user to view different attributes of the variables in a user-specified data set. When a variable is selected, a graphical display of the data is produced on the right-hand side of the window. The user can then select to visualize a graphical display of the individual patient profiles under the variable in a different window.

It is important to carefully document core ADHD symptoms at baseline to provide a reference point from which to evaluate effectiveness of treatment. Improvement in individualized patient outcomes are desired, such as (1) family and social relationships, (2) disruptive behavior, (3) completing required tasks, (4) self-motivation, (5) appearance, and (6) self-esteem. It is very important to elicit evaluations of the patient s behavior from family, school, and social environments in order to assess the preceding. Using standardized rating scales (e.g., Conners Rating Scales-Revised, Brown Attention-Deficit Disorder Scale, and IOWA Conners Scale) in both children and adults with ADHD helps to minimize variability in evaluation.29 After initiation of therapy, evaluations should be done every 2 to 4 weeks to determine efficacy of treatment, height, weight, pulse, and blood pressure. Physical examination or liver function tests may be used to monitor for adverse effects. 

Asthma is the most serious of the atopic diseases and has become epidemic, affecting more than 155 million individuals in the developed world. It is the most common chronic childhood disease in developed nations [1], and carries a very substantial direct and indirect economic cost worldwide [2]. A number of pharmacological treatments have been developed for asthma. These treatments have a modest efficacy overall, due in part to widely variable individual responses to asthma drugs. Because of such variability, it is clear that some of the substantial resources expended on asthma medication, estimated to exceed U.S. 3 billion per annum in the U.S. alone [3], would be better spent targeting those patients who... 

Pharmacokinetic concentration-time curves for a drug and ifs mefabolifes are used to identify primary exposure metrics such as AUC, or which are not time-dependent unlike the sequential measurements of concentration over time. A peak plasma concentration of a drug is often associated with a PD response, especially with an adverse event. There can be large inter-individual variability in the time-to-peak concentration, and closely spaced sampling times are often critical to determining the peak plasma concentration accurately in individual patients because of differences in demographics, disease states, and food effects, if any. All these elements are clearly spelled out in the protocols written to conduct these studies. 

In reality, risperidone acts as an atypical antipsychotic at doses up to 4-6mg/day. At higher doses, risperidone begins to act more like a typical antipsychotic, and EPS can become a problem. The dose at which this occurs for individual patients is quite variable. In elderly patients, even low doses can cause EPS. Whether this risk for EPS translates into a risk for TD after long-term use remains unknown. There is now considerable evidence that risperidone is also effective in treating mania and in augmenting antidepressants in particularly low doses. 

The therapeutic benefits and risks of a medicine, and therefore the choice of treatment for an individual patient, stem from evidence from a series of clinical trials. Taken together, these trials should reflect all likely therapeutic situations. From time to time, a particular problem arises that generates a new hypothesis. In order to obtain an answer to the specific question, we sometimes restrict the population sample to study subjects who do not possess a number of variables that may confound the outcome. In this manner, we move away from the realities of everyday clinical practice to an idealised, but artificial, environment. This is justifiable if the restriction is logical and if, with it, the hypothesis testing can be successfully completed. Otherwise, the issue may never be settled. 

MOMETASONE Administer mometasone by the orally inhaled route in patients 12 years of age and older. Individual patients will experience a variable time to onset and degree of symptom relief. Maximum benefit may not be achieved for 1 to 2 weeks or longer. 

Finally, there is variability of the treatment given and the underlying disease process for any individual patient. For example, a patient may have substantial ventricular mechanical dyssynchrony and have a successfully placed CRT device with appropriate lead locations. If very careful measures of ventricular performance are made, the patient s heart functions better with CRT on than off. However, if the patient suffers from a subsequent myocardial infarction or progressive ischemia, he may not improve clinically. Accordingly, at the end of a trial period, such a patient is termed a nonresponder even though he may be doing better with the device... 

Osteoarthritis is not a single disease entity because the different locations are exposed to different risk factors. Outcomes of OA vary among patients but are also variable in each individual patient. This depends on the joints involved, duration of disease, and the frequency the active inflammatory process is switched on and off. 

Short-Term Efficacy Although at least one study found no difference between alprazolam and placebo, several short-term studies have reported that alprazolam reduces the frequency and intensity of panic attacks (19, 20, 21, 22, 23, 24, 25, 26 and 27) (Table 13-2). In phase I of a cross-national collaborative study, including approximately 500 patients at eight sites, alprazolam was superior to placebo at the end of week 1 in improving spontaneous and situational panic attacks, anxiety, and secondary disability ( 23). At week 4, 50% of alprazolam patients and 28% of placebo patients were free of panic attacks. At week 8, however, 50% of those on placebo were also free of panic attacks, compared with 59% of those receiving alprazolam. These data reflect group efficacy and not individual responses over time. Furthermore, there was considerable variability and, at times, instability of response in individual patients. Explanations offered for the high rate of placebo response in this and other studies include ... 

Podophyllotoxin and its derivatives are active cytotoxic agents with specific affinity for the microtubule protein of the mitotic spindle. Normal assembly of the spindle is prevented, and epidermal mitoses are arrested in metaphase. A 25% concentration of podophyllum resin in compound tincture of benzoin is recommended for the treatment of condyloma acuminatum. Application should be restricted to wart tissue only, to limit the total amount of medication used and to prevent severe erosive changes in adjacent tissue. In treating cases of large condylomas, it is advisable to limit application to sections of the affected area to minimize systemic absorption. The patient is instructed to wash off the preparation 2-3 hours after the initial application, since the irritant reaction is variable. Depending on the individual patient s reaction, this period can be extended to 6-8 hours on subsequent applications. If three to five applications have not resulted in significant resolution, other methods of treatment should be considered. 

The statistical submodel characterizes the pharmacokinetic variability of the mAb and includes the influence of random - that is, not quantifiable or uncontrollable factors. If multiple doses of the antibody are administered, then three hierarchical components of random variability can be defined inter-individual variability inter-occasional variability and residual variability. Inter-individual variability quantifies the unexplained difference of the pharmacokinetic parameters between individuals. If data are available from different administrations to one patient, inter-occasional variability can be estimated as random variation of a pharmacokinetic parameter (for example, CL) between the different administration periods. For mAbs, this was first introduced in sibrotuzumab data analysis. In order to individualize therapy based on concentration measurements, it is a prerequisite that inter-occasional variability (variability within one patient at multiple administrations) is lower than inter-individual variability (variability between patients). Residual variability accounts for model misspecification, errors in documentation of the dosage regimen or blood sampling time points, assay variability, and other sources of error. 

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