Retrospective trials

The optimal dose of radiation therapy for patients with limited stage disease is unknown. Full dose radiation therapy is critical to achieve the therapeutic gain of local tumor control. Effective chemotherapy may allow a decrease in the radiation dose needed for local control (26). In the presence of chemotherapy, the radiation dose theoretically can be reduced 20% to control the tumor. Thus the dose for complete response, approx 70 Gy, can be decreased to 55 Gy (26). Local recurrence is still around 40-50% (27). Retrospective trials revealed that doses less than 40 Gy were not adequate for local control (28). 

ACE inhibitors can rednce proteinnria in patients with IgA nephropathy through their effect on the filtration barrier in the glomerular membrane. Several randomized trials and a large retrospective trial demonstrated that ACEIs moderately rednced proteinuria without improving renal function. Combined use of ACEIs and ARBs may have an additive effect on proteinuria reduction. However, their effects on renal function preservation is not known. Because hypertension is a negative prognostic indicator of IgA nephropathy and many of these patients already have left ventricular diastolic malfunction, despite being normotensive, early antihypertensive intervention with ACEIs or ARBs should be instimted. ... 

Azathioprine, a purine analogue, is another systemic immunosuppressant that may be helpful in severe cases of AD. Its main disadvantage, compared with cyclosporine, is a delayed onset of action of 4 to 6 weeks. Most reports of azathioprine use have been in uncontrolled, open, retrospective trials, and the use of inconsistent regimens in these trials makes determination of dosing schedules difficult. Despite numerous adverse effects—including myelosuppression, hepatotoxic-ity, and gastrointestinal disturbances—azathioprine can be helpful in reduction of AD disease activity. ... 

Reviewing the literature, there are further retrospective trials available, which show a good success rate and only minor complications (Table 6.2) (Callstrom et al. 2002 Dupuy 1989 Goetz et al. 2004b). 

Table 6.2. Different retrospective trials treating painful bone metastases using radiofrequency ablation...

A variety of data sources are available to inform interactive programs, including prospective data sets, retrospective databases, expert opinion, and unpub-lished/published literature. Time horizon, that is, the length of time into the future considered in the analysis over which costs and outcomes are projected, is very important here [26]. For example, if a clinical trial or the published literature only report short-term results for a chronic condition, the outcomes may come into question. This is where decision-analytic models may come... 

Trial validity is also grossly affected by the type of trial carried out. In schizophrenia there are several health-care decision models, retrospective mirror-image analyses (with or... 

To be useful to those concerned with choices in the allocation of health and social care resources, the data for economic evaluations need to be timely, relevant, credible and accurate (Davies, 1998). As a minimum, the costs associated with the interventions should be estimated from activity data, which quantify resources used, and price or unit cost data. Often evidence from well-controlled prospective trials with high internal validity is required to establish whether differences in economic end points are directly attributable to the interventions. However, the economic evaluations of acetylcholinesterase inhibitors estimated costs from retrospective analysis of available datasets Qonsson et al, 1999b), analysis of published literature (e.g. Stewart et al, 1998) and expert opinion (e.g. O Brien et al, 1999 Neumann et al, 1999). This means that it is not clear whether differences in costs were due to the anticholinesterase inhibitors or to other factors such as availability of services in different areas, the living situation of the patient, or disease severity. 

No direct comparison trials have been reported between the different thrombolytic agents in acute ischemic stroke. In a retrospective review of the results for acute stroke lAT performed at our center, we have found significantly higher rates of recanalization and good clinical outcome in the era in which lA UK was used versus the era in which UK was not available and lAT with rt-PA was the primary treatment. Conversely, in another retrospective study, Eckert et al. found no major difference between the recanalization rates of UK and rt-PA. 

In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

Qureshi et al." evaluated the timing of deterioration in patients with massive MCA strokes in a multicenter retrospective chart review. They found that 68% of patients manifested clinical deterioration by 48 hours, and nearly another 20% did so by 72 hours. Thus, the first 3-5 days appears to be the most crucial time for detecting patients at high risk for deterioration, although there was a small minority of patients who had deterioration at greater than 5 days from symptom onset. Early impairment in consciousness was also found to be predictive of mortality in one cohort of patients within a randomized chnical trial." One postmortem study of 192 patients found features in 45 patients that they postulate led to mahgnant ... 

Warfarin has not been adequately studied in non-cardioembolic stroke, but it is often recommended in patients after antiplatelet agents fail. One small retrospective study suggests that warfarin is better than aspirin.30 More recent clinical trials have not found oral anticoagulation in those patients without atrial fibrillation or carotid stenosis to be better than antiplatelet therapy. In the majority of patients without atrial fibrillation, antiplatelet therapy is recommended over warfarin. In patients with atrial fibrillation, long-term anticoagulation with warfarin is recommended and is effective in both primary and secondary prevention of stroke.12 The goal International Normalized Ratio (INR) for this indication is 2 to 3. 

CHD is the leading cause of death among women in the United States. Retrospective data indicated that HRT was associated with a decrease in risk of CHD by 30% to 50%.21 However, the results of recent RCTs demonstrate that HRT does not prevent or treat CHD in women and that it actually may cause an increase in CHD events. The HERS, published in 1998, was the first RCT conducted in women with established CHD. This trial demonstrated an increased incidence of CHD events within the first year of treatment with HRT and an increased risk of venous thromboembolism (VTE) and gallbladder disease. There was a trend of decreasing incidence... 

Major drawback Dose, indication, timing may not be standardized and therefore could confound associations if prospective, then same drawback as clinical trial if retrospective, same drawback as case-control Prospective study requiring follow-up time until endpoints develop to measure response... 

Clinical trials serve to assess the safety and efficacy of any potential new therapeutic intervention in its intended target species. In our context, an intervention represents the use of a new biopharmaceutical. Examples of other interventions could be, for example, a new surgical procedure or a novel medical device. Veterinary clinical trials are based upon the same principles, but this discussion is restricted to investigations in humans. Clinical trials are also prospective rather than retrospective in nature, i.e. participants receiving the intervention are followed forward with time. 

Prospectively and retrospectively evaluate, explain and extrapolate from the relationships between nonclinical trial findings and adverse clinical trial... 

In the broadest sense, genotyping can also be used in proof-of-principle trials and for individualization and modification of dose based on genotype. Associations between genotypes and clinical outcomes can also be explored retrospectively, as was the case for abacavir,20 21 but these are mainly exploratory and would need confirmation in a clinical trial prospectively. An important distinction was made between two types of genome-based enrichment the first type (preferred) is when there is a well-understood, genome-based pathophysiological ability to select responders and nonresponders, and the second type is when genomic-based predictions of differences in response are... 

In controlled trials, all of these treatments provided mixed results at best. A few patients seemed to benefit, but most did not. In retrospect, this is probably because patients with many different types of dementia were lumped together in these older stndies. We now believe that these treatments provided no benefit to the Alzheimer s disease patient bnt may have helped those with vascular dementia. 

The standard for radiation port size without chemotherapy for limited-stage SCLC is a relatively large port, which includes the original tumor volume with a 1.5-2 cm free margin (37,38). Included with the tumor are the involved lymph nodes as well as the neighboring uninvolved lymph nodes. A retrospective review of the SECSG trial re-... 

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