Optimum quality data

Presenting the design, methodology, and data to be collected in a study protocol. This study protocol specifies the manner of data collection and addresses all methodological considerations necessary to ensure the collection of optimum quality data for subsequent statistical analysis. 

Experimental methodology is concerned with all aspects of the implementation and conduct of a study. Its goal is to govern the conduct of the study such that optimum quality data are acquired. To enable subsequent data analysis and interpretation to provide the best answer to the research question of interest, the data acquired must be of optimum quality. The most sophisticated and computationally perfect... 

It is noted several times in this book that the goal of experimental methodology is to provide optimum quality data for subsequent statistical analysis. This is true, but there is also a very important intermediary between data acquisition and data analysis this is the field of clinical data management. In many cases, Data Management and Statistics fall under the same division within a company, and in some cases these tasks are handled by different divisions. Whichever is the case, it is vital to have statisticians involved in all discussions regarding database development and use. 

This last point is very important in two ways. First, throughout this book, the importance of optimum quality data is emphasized many times. In most cases, this comment is associated with acquiring the data, for example, measuring blood pressure as accurately as possible. However, since all of these data are entered into databases, data entry must be accurate A correct measurement that is stored incorrectly immediately lessens the quality of the overall data. Sometimes data are transferred from a measurement device electronically to the database, and sometimes data are manually entered into the database. Procedures to ensure accuracy, correctness, and completeness of data transfer are an essential part of data recording and management. Second, the storage of sensitive data (personal, medical) and proprietary data requires additional considerations to ensure that these data do not become accessible and available to unauthorized users. 

Since clinical trials can be conducted at multiple investigative sites (quite possibly in several countries) and can last for several years, it is essential for the acquisition of optimum quality data that the progress of the trial is monitored. Monitoring is... 

The previous chapter discussed the (currently) relatively loosely defined statistical approaches to safety data collected in clinical trials. In contrast, there are widely accepted statistical methods for demonstrating efficacy in clinical trials. As has been noted several times in this book, if the study design and methodology have been appropriate and have led to the collection of optimum quality data, the statistical analysis and interpretation of efficacy data are relatively straightforward. The clinical (biological) interpretation of efficacy data is typically not quite as clear-cut, but there are widely accepted methodologies that are very useful in this realm too. Of particular importance here is the expert judgment of the clinicians who will review the statistical results with the statisticians and the rest of the study team. 

Throughout this book there has been an emphasis on the acquisition of optimum quality data. As well as presenting this optimum quality data to regulatory agencies, it is imperative to present optimum quality data to readers of the clinical literature. It is of the utmost ethical importance that clinical communications are prepared to the highest degree of science and ethics, since clinicians may base the treatment of individual patients on evidence published in clinical communications in their practice of evidence-based medicine (see Section 13.7). 

Designing a study in an ethical manner such that the design is capable of producing optimum quality data. 

While the nature of the analyses of data from therapeutic confirmatory clinical trials is relatively straightforward compared with those undertaken in earlier stages of clinical development, supreme care should again be taken in all aspects of design, methodology, and analysis, since only then can optimum quality data be used to provide optimum answers to well-constructed research questions. Chapter 10 noted that safety data are typically presented descriptively at this time but that this may change in due course. By the time that therapeutic confirmatory trials are conducted, there should be a small number of precisely asked research questions that address the efficacy of the drug. 

Experimental methodology Acquiring optimum quality data. 

This functional definition makes clear that the discipline of Statistics is Indeed multi-faceted and essential throughout clinical trials. It is critical at the start of the clinical trial process so that a study can be designed appropriately to facilitate the collection of optimum quality data, which then need to be organized and managed correctly. These data are then described and analyzed, and the numerical results of these analyses are interpreted in the context of the particular study. Finally, the numerical results of the analyses and the authors interpretation of these results are presented to regulatory agencies to request permission to market the drug, and published in clinical communications to provide Information to physicians. 

Chapters 3 and 4 discuss how research questions are asked and answered in statistical language during clinical trials, and introduce the study designs and experimental methodologies that are used to acquire optimum quality data with which to answer our research questions. Chapter 5 discusses statistical ways of describing and summarizing these data. Chapter 6... 

It is unethical to include people in a study where poor design and/or poor methodology will lead to less-than-optimum quality data and therefore less-than-optimum quality answers to the study s research question. 

When the clinical research team has decided on their research question, and the appropriate study design and methodology to acquire optimum quality data with which to answer this question, all this information needs to be documented. The clinical study protocol is the document that is written for this purpose. Chow and Chang (2007, p 1) noted that the study protocol is "the most important document in clinical trials, since it ensures the quality and integrity of the clinical investigation in terms of its planning, execution, conduct, and the analysis of the data."... 

Equivalence and noninferiority trials are quite different from superiority trials in their design, analysis, and interpretation (although exactly the same methodological considerations apply to collect optimum quality data in these trials). Superiority trials continue to be our focus in this book, but it is important that you are aware of other designs too. Therefore, in Chapter 12 we discuss some of the unique features of these other design types. 

Collect optimum-quality data using optimum-quality experimental methodology. 

A given trial is conducted to collect optimum quality data with which to answer an identified and important research question. The data collected are intended to provide the most accurate answers to the research questions posed. A study protocol will often include both primary and secondary objectives, and also the associated primary and secondary endpoints. 

As is true across all research methodology, if the correct study design has been employed and rigorous methodology has permitted the acquisition of optimum-quality data, the computational analysis is typically not difficult. What is more difficult is the interpretation of the results and the appropriate degree of restraint needed to disseminate one s conclusions in a responsible manner. Given all of these considerations, the conduct and communication of a meta-analysis must be undertaken carefully, diligently, and responsibly. 

---