Patient population clinical practice

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Tension-type headache (TTH) is the most common primary headache disorder. It is often underrepresented in clinical practice, as many patients do not present for care.6 The term tension-type headache is used to describe all headache syndromes in which muscle contraction is the most significant factor in the pathogenesis of pain. The 1-year prevalence of TTH in the population ranges from 30% to 90%.6 It is more common in adult females. Environmental factors, as opposed to genetic predisposition, play a more central role in their development. Tension-type headaches can be further divided into episodic or chronic the mean frequency of attacks is 3 days per month in episodic disorders, and chronic TTH is defined as 15 or more attacks in a 1-month period.7 The estimated prevalence of chronic TTH is less than 5%.6 Some researchers believe that chronic TTHs represent a continuum of headache severity with migraine headache.8 When severe headaches are difficult to differentiate clinically, treatment should initially target TTH. 

The formula for calculating the budget of a GP practice must offer an unbiased estimator of the expected level of expenditure if each GP practice had a standard response to the needs of its population. Even if the considerable technical difficulties of establishing this formula could be overcome, the actual expenditure of a GP practice would differ from the budgeted amount due to characteristics of the patients not taken into account in the formula (socioeconomic characteristics, chronic diseases, private coverage and so on), variations in clinical practice between GP practices, random variations in the level of disease and price variations. For a population of 10 000 inhabitants (a reasonable mode for a GP practice) there is a one-third probability that the actual expenditure will deviate more than 10 per cent from a well-designed budget.22... 

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... 

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. 

When attempting to demonstrate the efficacy of a new drug, the use of data that do not favor this desired outcome is deemed appropriate. Then, if there is compelling evidence of the drug s efficacy, this evidence will be particularly noteworthy. This is the case for the ITT population. Analysis of the ITT population data may also provide estimates of treatment effects that are more likely to mirror those observed in subsequent clinical practice, i.e., the treatment of patients in real-world settings, should the drug subsequently be approved for marketing. 

Reproductive and Developmental Toxicity Studies The requirement for reproductive and developmental toxicity studies depends on the clinical indication and intended patient population. For example, when (1) no relevant animal species exists, (2) a biopharmaceutical is not used for pregnant women or women of child-bearing potential (3) there is a structurally comparable natural biopharmaceutical for which there is much experience in clinical practice, or (4) a biopharmaceutical is indicated for patients with minimal childbearing potential and indicated for those with serious diseases, reproductive, and developmental toxicity studies could be obviated. 

Variability in exposure to a drug leads to variability in the clinical response across a patient population (Rowland et al. 1985). Estimating the variability of the PK (pharmacokinetics) across a patient population requires data obtained from a large study, typically including more than 100 patients. For ethical and practical reasons, pharmacokinetic properties of a drug are difficult to study in large numbers of patients using the traditional approach. 

All IRBs are ultimately responsible for the unbiased determination of whether a proposal for clinical research is acceptable in terms of the standards of professional practice, the institution or individual undertaking the research, and the patient population. Therefore, proposals considered for approval at convened meetings must receive approval by the majority of the members present at that meeting. 

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