Discussions and insights

on statistical issues in life sciences

Latest Blogs

Statistical Software Validation: A Risk-Based Approach

Validation of statistical software is required for use in regulatory work. Many auditors expect to see the traditional IQ, OQ, PQ approach applied to the base system (SAS, R,... read more →

Should I Average My Pseudo-replicates?

A common discussion we at Quantics have with our clients surrounds the issue of pseudo-replicates. It’s an area of tension between scientist and statistician – pseudo-replicates reduce the cost... read more →

9th November 2023
Liam Cann | Matthew Stephenson | Connie Stewart and Jason Segall
All Blogs, Bioassay

USP 1033: Top 3 Highlights from New Draft Guidances

The United States Pharmacopeia (USP) guidance on biological assay validation, General Chapter <1033>, will soon be updated. In the leadup to the publication of the new guidance,... read more →

The Confidence Interval II: Standard Error & Central Limit Theorem

In part 1 of our series covering the confidence interval, we examined some of the basic statistical concepts associated with a bioassay. In particular, we saw that a... read more →

11th September 2023
Matthew Stephenson | Jason Segall and Holly Trochet
All Blogs, Bioassay, Uncategorised

What is Bioequivalence?

One of the greatest challenges in the development of new drugs and therapeutics is that it’s just plain expensive. The average spend on a drug which passes clinical trial... read more →

Un-confusing the Confidence Interval

A crucial acknowledgement of the scientific method is that no measurement will ever be perfect: results will always have associated variability, no matter... read more →

Non-Compartmental Analysis (NCA): The Basics of PK/PD Statistics, Part 1

Crucial in understanding the safety and efficacy of a drug are how it percolates through the body, or pharmacokinetics (PK), and how the body responds to its presence,... read more →

AI, Machine Learning and Medical Regulators

Unless you’ve been hiding under a rock for the past few months (and, honestly, who could blame you), you will have interacted with artificial intelligence (AI) in some form.... read more →

What is Parallelism in Bioassay?

In the most basic sense, relative potency bioassays consist of a comparison of the behaviour of a reference standard to that of a test sample. That process is not... read more →

Randomisation for Clinical Trials: A Guide

When James Lind (of Edinburgh, no less) first tested vitamin C as a cure for scurvy in 1747, he happened upon an experiment design which has persisted to this... read more →

22nd March 2023
Holly Trochet and Jason Segall
All Blogs, Clinical, Devices, Uncategorised

What is the 4PL Formula?

Picture the scene. You’re busily developing your assay and its data fits your chosen 4PL model beautifully. You’re just about to move onto validation—everything’s going so well!—but, out... read more →

15th March 2023
Ann Yellowlees | Taiki Yoshikawa and Jason Segall
All Blogs, Bioassay

Understanding Absolute and Relative Potency Assay for Optimal Results

Relative. Thanks for reading…But wait a moment! Have you ever stopped to ask why relative potency (RP) assays are the most common potency assay? Perhaps there are cases where... read more →

Population PK (PopPK): The What, The How, and The Why

Population Pharmacokinetics (PopPK) is the gold standard method of understanding drug safety and efficacy, particularly as it provides a unique insight into the variation of drug behaviour from person... read more →

31st January 2023
Matt Chapman-Rounds | Mai Shimodaira and Jason Segall
All Blogs, Clinical, HTA

Understanding Cut-Point Analysis for ADA Assays

What are the most important properties of a new drug? Ultimately, we want to ensure that any new therapy treats what it is designed... read more →

20th December 2022
Jason Segall
All Blogs, Bioassay

R² II: What should you use to measure Goodness-of-Fit?

In the first part of this series, we investigated the use of the coefficient of determination—R2—to measure goodness-of-fit. Specifically, we showed that it is an inadequate tool: a... read more →

Coefficient of Variation (CV) – a suitability criterion?

One of the most important concepts in bioassay is that of replication. Test samples are regularly replicated 2 or 3 times. Multiple response measurements at each dose will, in... read more →

26th October 2022
Jason Segall
All Blogs, Bioassay

R We Nearly Squared Yet? Why R² is a Poor Metric for Goodness-of-Fit

One of the most important metrics when analysing bioassay data is goodness-of-fit — how well does a dataset fit a chosen model? In development, this question can... read more →

Software: The BEBPA Sessions

This is the third blog responding to the software discussions at the BEBPA US 2022 conference. Blog One: formulae can be found here and Blog Two: Algorithms used can... read more →

Fitting Algorithms: The BEBPA Sessions

This is the second mini blog responding to the software discussions at the BEBPA US 2022 conference. Blog One: Formulae - can be found here. The key driver for... read more →

Statistical Model Formulae: The BEBPA Sessions

Myself, and my colleague Brooke, attended the BEBPA US virtual meeting last week and reported back on the presentation and round table discussions on relative potency software, including some... read more →

Choosing the best Parallel Line Analysis (PLA) software for your lab

Choosing the right Parallel Line Analysis (PLA) software for your lab is not an easy task. Whilst there are several packages available, and most can perform an adequate standard... read more →

Multiplicity in a Clinical Trial: Why is it Important?

This blog introduces the concept of multiplicity, why it is important and offers some techniques for dealing with the issue. When planning a clinical study, lots of thought is... read more →

Zero Dose Control – An extra data point for free!

At the recent BEBPA meeting, in response to the question: 'If you have a zero dose control on your plate do you include it in your... read more →

29th October 2021
Ian Yellowlees
All Blogs, Bioassay

Accuracy, Precision and Bias

Accuracy and Precision are properties of an experiment which are often conflated - not least because they are often synonymous in everyday conversation. In science, however, they have separate,... read more →

ML-NMR: the Future of Population Adjustment?

This is the third blog in our trilogy on techniques for population adjustment in network meta-analysis (NMA). Here we will focus on an approach called Multi-Level Network Meta-Regression (ML-NMR),... read more →

Outliers – To Remove, Or Not To Remove?

It has been sometime since I have set foot in a lab, but the thought of seeing outliers in my data still sends a shiver down my spine –... read more →

22nd February 2021
Ishara Fernando
All Blogs, Bioassay

What is a Simulated Treatment Comparison, and can it help my HTA submission?

In this blog we will describe an alternative approach to indirect comparison - Simulated Treatment Comparison (STC) and discuss the key aspects to consider when looking to use the... read more →

12th November 2020
Matt Chapman-Rounds
All Blogs, HTA

Failing Goodness-of-Fit: How to Combat the F-test Headache

We have all experienced the frustration (and sometimes utter dejection!) of performing a bioassay to what you thought was near perfection only to come back, analyse the data, and find... read more →

Sample Size and Other Common Medical Device Trial Design Errors that Matter

Designing and running a clinical trial for a medical device is expensive, and to avoid wasting money, time and risking the validity of the trial, it is important to get... read more →

28th October 2020
Ian Yellowlees
All Blogs, Devices

Hidden Consequences of Interim Analyses & Adaptive Trial Options

Interim analyses are common in medical device trials for a variety of reasons. Just having a look is fine, but if the outcome of the analysis could change the conduct... read more →

20th August 2020
Ann Yellowlees
All Blogs, Devices

Unanchored comparison between the single arm trials A and C and between B and C

Matching Adjusted Indirect Comparison (MAIC) – 4 Practical steps to follow

When comparing trial outcomes using standard network meta-analysis (NMA), the assumption is that populations in different trials do not differ in any characteristics that may impact the treatment effect... read more →

29th June 2020
Gustaf Rydevik
All Blogs, HTA

Vaccine Development: Correlates of Protection Explained

Correlates of protection in determining vaccine efficacy is a topic of particular interest, given the current COVID-19 climate and the spotlight on vaccine development. Here at Quantics, we have... read more →

A Review of Statistical Hypothesis Testing

A clinical trial is often designed to demonstrate that a new treatment is performing better than the currently available treatment. To do this, one must show that there is a... read more →

Bioassay Simulation: Reduce Lab Work

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... read more →

Post Covid 19 – Handling Missing Data in Clinical Trials

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... read more →

Pseudo-replicates and Bioassay

This blog explains the difference between true replicates and pseudo-replicates, and discusses the problems that may arise if this difference is ignored or misunderstood in bioassay statistical analysis. Quality... read more →

31st January 2020
Ian Yellowlees
All Blogs, Bioassay

pseudo-replicates: Pure Error Bioassay 8 doses

When is Pure Error for Bioassay an Error?

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... read more →

6th September 2019
Ian Yellowlees
All Blogs, Bioassay

ELISA Analysis: The Bursa-Yellowlees Method

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... read more →

Population Adjustment in Network Meta-analysis

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... read more →

How to Set Suitability Criteria for Relative Potency Bioassays

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... read more →

Possible outcomes of a NI Clinical Trial

What is a Non-inferiority Clinical Trial?

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... read more →

22nd October 2018
Francis Bursa
All Blogs, Clinical

Suitability Tests for Bioassay

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... read more →

31st August 2018
Francis Bursa
All Blogs, Bioassay

ISS & ISE: Integrated Summary of Safety and Integrated Summary of Effectiveness

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... read more →

Extrapolating Clinical Trial Data Using Survival Analysis

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... read more →

Survival analysis for LD50 and vaccine challenge assays

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... read more →

How to Combine Relative Potencies for Bioassay

Welcome to our blog on combining relative potencies. In this blog, we’ll review the methods recommended by the United States Pharmacopeia (USP) and European Pharmacopoeia (PhEur) for combining relative... read more →

20th February 2018
Francis Bursa
All Blogs, Bioassay

Bootstrap method in dose-response modelling

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... read more →

10th November 2017
Stephen Mackie
All Blogs, Ecotox

Survival Analysis for Clinical Trials

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... read more →

9th November 2017
Sydney Toupin
All Blogs, Clinical

Software for Bayesian Network Meta-Analyses

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... read more →

13th September 2017
Sydney Toupin
All Blogs, HTA

Planning a Network Meta-analysis

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... read more →

19th July 2017
Kelly Fleetwood
All Blogs, HTA

Clinical Trial Study populations venn diagram

Study Populations: Clinical Trial Design

Study Populations The aim of a clinical trial is to make a calculated judgement about the likely clinical effectiveness results that would be seen if the treatments tested were... read more →

Complications of fitting 4PL and 5PL models to bioassay data

We have previously discussed the 4 parameter logistic (4PL) model. This is a symmetrical S-shaped curve with the equation \[y=D+\frac{A-D}{1+e^{B\left(\log(dose)-C\right)}}\] for a response y. Sometimes you may see slightly... read more →

The Jonckheere-Terpstra test for ordered differences

Recently our team at Quantics were working on an analysis for an ecotoxicology client which called for us to use the Jonckheere-Terpstra test for ordered differences which is recommended... read more →

continuouse clinical trial design endpoint

Clinical trial design – Comparing clinical trial endpoint summaries

This 3rd clinical trial design blog from Quantics Biostatistics takes an introductory look at how the various types of clinical endpoints (which we introduced in our previous blog) determine... read more →

24th January 2017
Ann Yellowlees
All Blogs, Clinical

Improving confidence limits for concentration-response models with quantal data

In ecotoxicology statistics there are three main types of data: continuous discrete quantal / binary Continuous data is that which can take a (numerical) value over a continuous range (e.g.... read more →

11th October 2016
Daniel James
All Blogs, Ecotox

Endpoints: Clinical Trial Design

In our last blog we discussed sample size choice and identified the key information that your statistician needs to know and why. In our second clinical trial design blog we shall... read more →

14th September 2016
Ann Yellowlees
All Blogs, Clinical

The key assumptions of network meta-analysis

Like all statistical analyses, network meta-analysis relies on a specific set of assumptions. In this second post, we’ll look at the key assumptions of network meta-analysis. In order to... read more →

29th July 2016
Kelly Fleetwood
All Blogs, HTA

Ecotoxicology – NOEC and LOEC

Welcome to Quantics' ecotoxicology blog. This blog will explore some of the interesting topics in ecotoxicology statistics with particular focus on the Organisation for Economic Cooperation and Development (OECD)... read more →

12th July 2016
Daniel James
All Blogs, Ecotox

What is Relative Potency?

Relative potency (RP) refers to the dose of a test sample required to produce the same response in an assay as a dose of a reference sample. Since we... read more →

How to Inform Sample Size Calculations for Clinical Trials

Welcome to Quantics' Clinical blog. This blog will explore some of the statistical aspects of clinical trial design including study design, sample size, data management and analysis planning. The aims... read more →

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