Study Design - Success or Failure
Study design is the first and most important step in planning a successful study.
In case of one sample or a limited number of samples, no study needs to be designed.
In case of studies with many samples, like a clinical study or an environmental study, the study needs to be well designed in many aspects.
A clinical study with many samples, easily several hundreds or thousands, requires the following:
The cohort must include affected individuals with a comprehensive clinical diagnosis and non-affected individual, best healthy individuals. Individuals with similar symptoms as the affected ones, but with a different clinical diagnosis should be added, if available.
The cohort must include all demographic aspects, as gender, age groups, lifestyle, ethnicities and more, to be discussed when planning the study.
Sample collection must be done following a strict protocol, every step in sample collection and consecutive preparation must be documented.
In most cases not all samples can be processed or analysed together, smaller batches have to be generated. These batches have to reflect the composition of the complete sample set, stratification. This can become quite complicated and needs to be discussed in view of the study.
The finally selected samples for the batch need to be randomised to avoid analysing samples with the same background together.
To analyse the samples, batch processing quality control samples (BQC) and technical quality control samples (TQC) have to be added.
Batch processing quality control samples are samples which are processed together with the selected samples of one batch. All processing steps have to be carried out with this sample. Usually this sample is generated by combining an aliquot from all samples in the study. A BQC sample is processed after 10 study samples and will show if anything goes wrong during the sample processing.
Another uncertainty is the instrument performance. Especially mass spectrometry coupled with liquid chromatography may lose sensitivity over time. The instrument also needs stabilisation before the real samples are analysed. The TQC sample is one single sample prepared in a larger amount and ideally enough for the whole study. It is analysed 5 - 10 times before the batch with the TQC until performance has stabilised, within the batch before or after the BQC and at the end of the batch 5 - 10 times. TQC helps to correct the batch in case of instrument performance changes.
A number of blanks have to be added also. Taking all these additional samples into account, the number of finally analysed samples easily doubles. This is an important aspect for the calculation of the costs of the project and the timelines.
A number of publications available about study design, list is following soon.
In case of one sample or a limited number of samples, no study needs to be designed.
In case of studies with many samples, like a clinical study or an environmental study, the study needs to be well designed in many aspects.
A clinical study with many samples, easily several hundreds or thousands, requires the following:
The cohort must include affected individuals with a comprehensive clinical diagnosis and non-affected individual, best healthy individuals. Individuals with similar symptoms as the affected ones, but with a different clinical diagnosis should be added, if available.
The cohort must include all demographic aspects, as gender, age groups, lifestyle, ethnicities and more, to be discussed when planning the study.
Sample collection must be done following a strict protocol, every step in sample collection and consecutive preparation must be documented.
In most cases not all samples can be processed or analysed together, smaller batches have to be generated. These batches have to reflect the composition of the complete sample set, stratification. This can become quite complicated and needs to be discussed in view of the study.
The finally selected samples for the batch need to be randomised to avoid analysing samples with the same background together.
To analyse the samples, batch processing quality control samples (BQC) and technical quality control samples (TQC) have to be added.
Batch processing quality control samples are samples which are processed together with the selected samples of one batch. All processing steps have to be carried out with this sample. Usually this sample is generated by combining an aliquot from all samples in the study. A BQC sample is processed after 10 study samples and will show if anything goes wrong during the sample processing.
Another uncertainty is the instrument performance. Especially mass spectrometry coupled with liquid chromatography may lose sensitivity over time. The instrument also needs stabilisation before the real samples are analysed. The TQC sample is one single sample prepared in a larger amount and ideally enough for the whole study. It is analysed 5 - 10 times before the batch with the TQC until performance has stabilised, within the batch before or after the BQC and at the end of the batch 5 - 10 times. TQC helps to correct the batch in case of instrument performance changes.
A number of blanks have to be added also. Taking all these additional samples into account, the number of finally analysed samples easily doubles. This is an important aspect for the calculation of the costs of the project and the timelines.
A number of publications available about study design, list is following soon.