Retrospective analysis

The regulators do, however, recognise that pre-planning is not always possible. 

CPMP (2001) Points to Consider on Application with 1. Meta-Analysis  

It is still important even in this retrospective setting to write a protocol so that the meta-analysis can be performed as objectively as possible. The CPMP Points to Consider paper lists the prerequisites that are needed for such a retrospective analysis. 

There are overwhelming advantages to conducting safety activities which are integrated into the product lifecycle from conception. In particular, the opportunity to mitigate identified hazards at the design stage can result in more robust controls and 

A key danger in the retrospective approach is to fall into the trap of conveniently building the safety argument around selective evidence which happens to be at hand. To do so runs the risk of forcing the safety case to articulate an artificially rosy picture of the world. It can be easy to assume that a much-loved system that has been in operation for many years must be intrinsically safe. That is not to say that it is unsafe but one should actively question whether the data which happens to be available can truly and objectively substantiate the safety case s claims. In some circumstances it may be appropriate to undertake the hazard assessment in a virtual vacuum of operational knowledge perhaps involving personnel who are somewhat removed from its day-to-day business. In this way appropriate controls can be developed and more objectively be tested to determine whether they can be traly validated. 

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A number of interactive program developers advocate retrospective analyses and modeling as alternatives to prospective data sources. These sources... 

Due to the issues surrounding the analysis of archived samples, most microarray-based oncology studies have relied on prospective analyses—running samples as they become available, rather than retrospective analyses—running archived samples. While the prospective analysis tends to provide excellent-quality data, the associated clinical data from archived samples tends to be of greater value. In particular, in obtaining archived samples, it is possible to concentrate on those patients for which outcome information is known (e g., survival rates, recurrence, treatment success, and so on). 

Many newer technologies from labeling techniques to array designs are helping to combat the issues of dealing with FFPE samples, opening the door to larger and more robust retrospective analyses. 

Several retrospective analyses in stage IV gemcitabine/cisplatin-treated NSCLC show that patients with NER-defective tumors (e.g., low ERCC 1 or RRM1 mRNA levels) have a median survival of 15 months. However, the predictive value of low ERCCl mRNA levels found in our original study (31) was not borne out by our second study with Italian patients, in which low ERCCl levels showed a non-significant trend towards better survival (unpublished data). 

The clinical, biochemical, and thyroid imaging characteristics of thyrotoxicosis resulting from interferon alfa treatment have been retrospectively analysed from data on 10 of 321 patients with chronic hepatitis (75 with chronic hepatitis B and 246 with chronic hepatitis C) who developed biochemical thyrotoxicosis (505). Seven patients had symptomatic disorders, but none had ocular symptoms or a palpable goiter. Six had features of Graves disease that required interferon alfa withdrawal in four and prolonged treatment with antithyroid drugs in all six. Three presented with transient thyrotoxicosis that... 

The Swedish Environmental Specimen Bank is a centralized storage bank that has been operational for 20 years. It conducts annual sampling of a variety of environmental and human specimens for use in a number of studies, including retrospective analyses. Regional banks store human blood for use in these studies (European Commission 2004). 

When all 26 cases of vertebral artery dissection during the period 1989-99 were retrospectively analysed in a tertiary Canadian academic center, possible precipitating factors were identified in 14 patients (171). Chiropractic spinal manipulation and sporting activity were the most common factors (11% and 15% respectively). 

The results of a therapeutic interchange program, in which 78 patients with acid peptic disease requiring proton pump inhibitor therapy (both newly diagnosed patients and those previously stabilized on omeprazole) were treated with lansoprazole, have been retrospectively analysed (12). Although the switch was associated with considerable pharmaceutical savings, there was an overall lansoprazole-associated failure rate of 28%. Reported lack of efficacy required withdrawal of lansoprazole in 15%, while adverse effects required withdrawal of lansoprazole in 13% of patients (versus none with omeprazole). The main adverse effect was diarrhea. 

There has been concern that overtreating high BP in patients with coronary artery disease may bring about more harm than good (termed the J-curve phenomenon). Since coronary blood flow occurs during diastole, the rate of flow is directly influenced by the DBP. Therefore, excessively reducing DBP may compromise coronary perfusion, especially in patients with fixed coronary artery stenosis, and lead to myocardial infarction. This concern has been theoretical based on retrospective analyses, and prospective studies have not found a J-curve until DBPs were very low (<60 mm Hg). However, this controversy has resurfaced because a post-hoc subgroup analysis of the INVEST study has shown a J-curve in patients with DBP less than 84 mm Hg. 

Retrospective analyses of cUnical studies suggest that females are more susceptible to aminoglycoside nephrotoxicity than males [17]. This is in contradiction to the increased susceptibility of male rodents to aminoglycosides [21]. In experimental animals with strep-tozotocin diabetes, nephrotoxicity and renal drug uptake are markedly reduced [22, 23]. There seems to be no clinical counterpart to this experimental observation. 

After these findings, retrospective analyses of phytoplankton monitoring data and several new severe intoxications affecting thousands of people in different European countries allowed experts to confirm the association of these events with different Dinophysis spp. D. acuminata, D. acuta, D. nor-vegica) in NW Spain [19], the Netherlands [20], Norway [21,22], western Sweden [23], and Brittany... 

Batch analysis results—Complete batch analysis data should be included for key batches prepared throughout the development program, including, if practical, material manufactured at the site(s) that will supply material for commercial purposes. These test results should be provided against the specifications in place at the time of the release of the batch for its intended use. Often, it is valuable to include retrospective analyses of key batches using techniques established or modified subsequent to their initial release. This could be particularly beneficial for impurities, assuming the impurity profile method(s) were modified during development. It is also expected that information on the manufacture (date, size, location) and use of each listed batch (clinical, safety, stability, market product, etc.) be included in the application. 

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