Ensuring scientific validity

In order to ensure that a meta-analysis is scientifically valid it is necessary to plan and conduct the analysis in an appropriate and rigorous way. It is not sufficient to retrospectively go to a bunch of studies that you like the look of and stick them together  

The CPMP (2001) Points to Consider on Application with 1. Meta-Analysis 2. One Pivotal Study indicates that it is good practice to write a protocol for the meta-analysis  

This document then goes on to list the issues that should be covered by that protocol  

Writing a protocol in this way is important for a meta-analysis that is prespecified within a development plan, but, in order to ensure its integrity, it is maybe 

Normand (1999) expands on many of the issues surrounding the planning of a meta-analysis and the reader is referred to this article for more information. 

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The NRC subcommittee s review of the AEGL reports prepared by NAC and its contractors involves oral and written presentations to the subcommittee by the authors of the reports. The NRC subcommittee provides advice and recommendations for revisions to ensure scientific validity and consistency with the NRC guideline reports (NRC 1993, in press). The revised reports are presented at subsequent meetings until the subcommittee is satisfied with the reviews. Because of the enormous amount of data presented in the AEGL reports, the NRC subcommittee can not verify all the data used by NAC. The NRC subcommittee relies on NAC for the accuracy and completeness of the toxicity data cited in the AEGLs reports. 

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. 

The challenges of intervention research do not end with the preparation of a clinically relevant, scientifically valid, and ethically acceptable protocol. Conduct of the study requires constant attention to both the clinical and experimental components of the trial. Some protocol deviations can be expected in almost every study, but procedures should be in place to minimize both their number and impact, as deviations decrease the assay sensitivity of the experiment and thus the likelihood of detecting treatment effects. A discussion of the monitoring procedures to ensure the quality of the re-... 

FDA at an early stage to ensure that they will be accepted as scientifically valid. The statistical analysis section prepared after the basic protocol has been finalized should describe the following ... 

A brief discussion of each feature can be found later in this chapter. Underlying the epidemiological method are two assumptions first, that disease does not occur randomly and, second, that systematic study can identify factors that cause or can prevent disease (Hennekens and Buring 1987). Those design features help to ensure the scientific validity of human data, and they underscore the added strength and utility of epidemiological data that contribute to assessment of human health risk from toxicological hazards. 

Adsorption energy studies serve a very useful purpose in three main areas (1) to provide chemical engineering data (2) to investigate adsorption mechanisms and (3) to characterize the energetic heterogeneity of solid surfaces. To ensure that the evaluated adsorption energies have scientific validity, it is essential that the... 

Clinical Review. The reviewing medical officer, who is generally a physician, evaluates the clinical protocols to ensure (1) that subjects will not be exposed to unreasonable or unnecessary risks during clinical triads and (2) that Phase 2 and Phase 3 trials (generally not submitted in the initial IND filing) are adequate in design to provide scientifically valid data. 

DOE is the fastest route to a profitable, reliable, robust, validated process. DOE s requirement of a rigorous design methodology that passes peer review with the scientists most knowledgeable about the process ensures scientific soundness. The depth of DOE s statistical foundation that enables the measurement of multiple effects and interactions in a single set of experiments proves DOE s statistical validity. DOE is also a resource conservator, since it requires less time and... 

Test systems are the tools with which the purpose of the study, the search for, and the investigation of, effects produced by a test item, or the elucidation of its properties can be fulfilled. Test systems may therefore be any biological, chemical or physical system or a combination thereof used in a study . Since the test systems are the instruments for the generation of the safety data, documented evidence for their adequacy and integrity, as well as their properties has to be provided in order to ensure the scientific validity of the studies conducted. 

The applicant must submit complete copies of dossier to the EMEA, and directly to each of the rapporteurs. The EMEA are allowed 14 days to validate the application to ensure that it is complete and in accordance with the regulations, after which the rapporteurs can commence the scientific evaluation. The review process involves considerable feedback between the rapporteurs, the CHMP and the applicant, central to which can be achieving agreement on the final text of the SPC, labels and leaflet. The rapporteurs are required to deliver preliminary assessment reports to the CHMP within 80 days of the start of the review process. The applicant is also copied on the report. Over the next 40 days issues raised in... 

CICADs are concise documents that provide summaries of the relevant scientific information concerning the potential effects of chemicals upon human health and/or the environment. They are usually based on selected national or regional evaluation documents or on existing EHCs. Before acceptance for publication as CICADs by IPCS, these documents undergo extensive peer review by internationally selected experts to ensure their completeness, accuracy in the way in which the original data are represented, and the validity of the conclusions drawn. 

A clinical trial is an experiment and not only do we have to ensure that the clinical elements fit with the objectives of the trial, we also have to design the trial in a tight scientific way to make sure that it is capable of providing valid answers to the key questions in an unbiased, precise and structured way. This is where the statistics comes in and statistical thinking is a vital element of the design process for every clinical trial. 

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