Bioassay simulation can be used during assay development maintenance to supplement and complement the information gained from lab experiments. Bioassay simulation assumes that the available real data is a representative sample of all the real data sets that might be created over the life of the assay. The mathematical properties of this sample can be…
COVID-19 disruption of clinical trials is likely to result in missing data, disrupted timelines, and perhaps patient population changes. We thought we would dedicate a blog post to the actions that can be considered when a study is facing the issue of missing data. The COVID-19 situation is clearly still developing and regulators are still…
Here, we investigate the difference between true replicates and pseudo-replicates, and discuss the problems that may arise if this difference is ignored or misunderstood in bioassay statistical analysis. Quality Control by sampling Consider a manufacturing process that makes widgets. To check the quality of a batch, a number of widgets randomly selected from the batch…
Software systems for calculating relative potencies and other bioanalytical results often provide a choice of variance estimation method, usually: Residuals, Lack of fit Error and Pure Error. This defines how the confidence limits on the reportable result are calculated. So which should you choose? The answer is simple. If the reportable result is calculated in…
Interpolation analysis is used to find the concentration of a substance in a sample. For biologics, this is often used in ELISA and other bioanalytic analyses. This blog introduces interpolation analysis for ELISA and presents a new method developed by Quantics. The Bursa-Yellowlees Method uses the available ELISA data more effectively and greatly simplifies the…
In an ideal world, a single randomized controlled trial (RCT) would be used to compare and evaluate the individual treatment effects for all possible treatments of interest. Of course, this is often not feasible, in which case network meta-analysis (NMA) can be used to link RCTs with common treatment arms and compare treatments across different…
We previously discussed the purpose of system suitability tests and sample suitability tests and gave some examples of each. However, we did not explain how to actually set the limits for these tests: suitability criteria. In this blog we will discuss this and go through a couple of examples of how to set suitability criteria…
In this blog we will discuss a particular type of clinical trial design, the non-inferiority trial. We will explain the difference between non-inferiority trials and more typical clinical trial designs to help build understanding of the non-inferiority limit. Standard clinical trials usually aim to show that a new treatment is better than an existing one….
Suitability tests for bioassay are often confusing. In this blog, we discuss the two types of suitability tests: System suitability tests and Sample suitability tests. The blog is deliberately simplistic in approach to aid basic understanding. In practice, the use of the various System and Sample suitability criteria may be more complex. We’ll focus mainly…
A standard pairwise meta-analysis can compare the efficacy or safety of exactly two treatments that have been directly compared in head-to-head clinical trials. However, in practice, there are often many potential treatments for a single disease. Policy-makers, physicians and patients need to be able to select the best treatment from amongst the many potential options….
What do ISS & ISE mean? ISS & ISE stand for integrated summary of safety and integrated summary of effectiveness, respectively. These are not merely summaries, as the name might suggest, but rather documents comprised of integrated analyses of the safety and effectiveness of a study drug [1]. In other words, the results from all…
In our previous blog on survival analysis, we touched on some of the characteristics of survival data and various fundamental methods for analysing such data, focusing solely on non-parametric methods of analysis which only estimate the survival function at time points within the range of the raw data. I mentioned in the conclusion that parametric…
LD50 assays and challenge assays both measure the time to an event, often death, for each animal. However the standard statistical approach to the analysis of the data treats the endpoint as binary – alive / dead – at a given point in time. This is inefficient use of the data. Here, we will recommend…
It often happens that the precision required from a relative potency (RP) bioassay cannot be achieved using a single plate. In this situation the usual approach is to repeat the assay two or more times1. Each run of the assay will give a separate relative potency result. These are then combined to give a single…
In a previous blog, we looked at fitting dose-response models to quantal data in ecotoxicology scenarios. To recap, quantal data refers to data where the response variable takes a binary value. A number of organisms are exposed to a dose of test substance and then after a set period of time the number exhibiting a…
We have discussed Handling Missing Data in Clinical Trials elsewhere, and mentioned a kind of missing data known as ‘censoring’. In this blog we focus on techniques for dealing with this, known as ‘Survival Analysis’. Censoring occurs in time-to-event data (the time from a defined origin until the event of interest), when the event has…
In this post we examine the statistical software available for conducting Bayesian network meta-analyses (NMA). The first two sections provide some background information and a review of the available software – we hope this section will be of interest to all of our readers. The final section provides an introduction to conducting NMA in Stan…
Our clients sometimes tell us that they don’t want to use response transformations since it feels like an unwarranted manipulation of the data. However, there is little point in avoiding a transformation just to get results that may be wrong. In this blog we explain when you should consider transforming the response, and how to…
Many of our readers will be familiar with our paper “Parallelism in Practice” (PDA Journal of Pharmaceutical Science and Technology, 2015) and how we examined the common methods used for evaluation of parallelism for bioassay. Here, we explain why the usual way of thinking about parallelism doesn’t always make sense when dealing with biosimilars; we…
Most network meta-analyses will consist of six key stages – developing the protocol, performing the systematic review, conducting the feasibility assessment, preparing the statistical analysis plan, running the analyses and reporting the results. In this post, we give a brief overview of each of these stages, and suggest strategies for ensuring that your network meta-analysis…