# Professor Adrian Mander

Professor in Medical Statistics and Director of Statistics

- Available for postgraduate supervision

## Overview

I am the Director of Statistics and Professor of Medical Statistics at the Centre for Trials Research (CTR) and I took up this post in 2019. All the statisticians at CTR are within my team and as of 2021 we have 21 statisticians supporting both internal and external trials. I am excited to be inside a large clinical trials unit and lead a large team of statisticians. There is a great wealth of knowledge among the team and we are building a centre of excellence in adaptive trial design.

## Biography

I did a PhD in spatial game theory at Sheffield Unviersity under the supervisors Chris Cannings and Paul Blackwell in 1995. On the maths genealogy you will notice that via supervisors I am a direct descendant from R. Fisher.

Then I did a postdoc at the LSHTM medical statistics group until 1997 working in Stuart Pocock's group on asthma trials

I moved to Cambridge to work with David Clayton at the MRC Biostatistics Unit on problems in statistical genetics and missing data until 2001.

I worked at GSK in their Clinical Pharmacology group for a year then their Worldwide Epidemiology group until 2005.

I moved back to Cambridge to take up a position in the MRC Human Nutrition Research unit as head of statistics.

Then I went back to the MRC Biostatistics Unit to become one of the Directors of the network of Hubs for Trials Methodological Research for 10 years.

## Publications

### 2021

- Bennett, M.et al. 2021. A novel equivalence probability weighted power prior for using historical control data in an adaptive clinical trial design: a comparison to standard methods. Pharmaceutical Statistics 20(3), pp. 462-484. (10.1002/pst.2088)
- Law, M., Grayling, M. J. and Mander, A. P. 2021. A stochastically curtailed two‐arm randomised phase II trial design for binary outcomes. Pharmaceutical Statistics 20(2), pp. 212-228. (10.1002/pst.2067)

### 2020

- Dimairo, M.et al. 2020. The Adaptive designs CONSORT Extension (ACE) Statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. BMJ 369, article number: m115. (10.1136/bmj.m115)
- Dimairo, M.et al. 2020. The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. Trials 21, article number: 528. (10.1186/s13063-020-04334-x)
- Pallmann, P.et al. 2020. Designing and evaluating dose-escalation studies made easy: the MoDEsT web app. Clinical Trials 17(2), pp. 147-156. (10.1177/1740774519890146)
- Bennett, M. and Mander, A. P. 2020. Designs for adding a treatment arm to an ongoing clinical trial. Trials 21(1), article number: 251. (10.1186/s13063-020-4073-1)

### 2019

- Grayling, M. J.et al. 2019. A review of perspectives on the use of randomization in phase II oncology trials. JNCI: Journal of the National Cancer Institute 111(12), pp. 1255-1262. (10.1093/jnci/djz126)
- Wych, J., Grayling, M. J. and Mander, A. P. 2019. Sample size re-estimation in crossover trials: application to the AIM HY-INFORM study. Trials 20(1), article number: 665. (10.1186/s13063-019-3724-6)
- Dimairo, M.et al. 2019. Introducing the Adaptive designs CONSORT Extension (ACE) Statement to improve reporting of randomised trials that use an adaptive design (P-7). Presented at: 5th International Clinical Trials Methodology Conference (ICTMC 2019), Brighton, UK, 6-9 October 2019. BioMed Central pp. -., (10.1186/s13063-019-3688-6)
- Grayling, M. J., Mander, A. P. and Wason, J. M. S. 2019. Two-stage adaptive designs for three-treatment bioequivalence studies. Statistics in Biopharmaceutical Research 11(4), pp. 360-374. (10.1080/19466315.2019.1654911)
- Grayling, M. J., Wason, J. M. S. and Mander, A. P. 2019. Exact group sequential designs for two-arm experiments with Poisson distributed outcome variables. Communications in Statistics - Theory and Methods 50(1), pp. 18-34. (10.1080/03610926.2019.1628273)
- Grayling, M. J., Mander, A. P. and Wason, J. M. S. 2019. Admissible multiarm stepped-wedge cluster randomized trial designs. Statistics in Medicine 38(7), pp. 1103-1119. (10.1002/sim.8022)
- Wheeler, G. M., Sweeting, M. J. and Mander, A. P. 2019. A Bayesian model‐free approach to combination therapy phase I trials using censored time‐to‐toxicity data. Journal of the Royal Statistical Society: Series C 68(2), pp. 309-329. (10.1111/rssc.12323)

### 2017

- Wheeler, G. M., Sweeting, M. J. and Mander, A. P. 2017. Toxicity-dependent feasibility bounds for the escalation with overdose control approach in phase I cancer trials. Statistics in Medicine 36(16), pp. 2499-2513. (10.1002/sim.7280)
- Wheeler, G. M.et al. 2017. Modelling semi-attributable toxicity in dual-agent phase I trials with non-concurrent drug administration. Statistics in Medicine 36(2), pp. 225-241. (10.1002/sim.6912)

### 2016

- Spencer, A. V.et al. 2016. An adaptive design for updating the threshold value of a continuous biomarker. Statistics in Medicine 35(27), pp. 4909. (10.1002/sim.7042)

### 2015

- Mander, A. P. and Sweeting, M. J. 2015. A product of independent beta probabilities dose escalation design for dual-agent phase I trials. Statistics in Medicine 34(8), pp. 1261--1276. (10.1002/sim.6434)

### 2013

- Walker, C. G.et al. 2013. Genetic predisposition to an adverse lipid profile limits the improvement in total cholesterol in response to weight loss.. Obesity 21(12), pp. 2589-95. (10.1002/oby.20328)
- Sweeting, M., Mander, A. and Sabin, T. 2013. bcrm: Bayesian Continual Reassessment Method designs for Phase I dose-finding trials. Journal of Statistical Software 54(13) (10.18637/jss.v054.i13)
- Harrington, J. A.et al. 2013. Adaptive designs for dual-agent phase I dose-escalation studies. Nature Reviews Clinical Oncology 10(5), pp. 277-288. (10.1038/nrclinonc.2013.35)

### 2012

- Browning, L. M.et al. 2012. Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish. American Journal of Clinical Nutrition 96(4), pp. 748-758. (10.3945/ajcn.112.041343)
- Sweeting, M. J. and Mander, A. P. 2012. Escalation strategies for combination therapy Phase I trials. Pharmaceutical Statistics 11(3), pp. 258-266. (10.1002/pst.1497)
- Wason, J. M. S. and Mander, A. P. 2012. Minimizing the Maximum Expected Sample Size in Two-Stage Phase II Clinical Trials with Continuous Outcomes. Journal of Biopharmaceutical Statistics 22(4), pp. 836-852. (10.1080/10543406.2010.528104)
- Walker, C. G.et al. 2012. Genetic predisposition to type 2 diabetes is associated with impaired insulin secretion but does not modify insulin resistance or secretion in response to an intervention to lower dietary saturated fat. Genes and Nutrition 7(4), pp. 529-536. (10.1007/s12263-012-0284-8)
- Mander, A. P.et al. 2012. Admissible two-stage designs for phase II cancer clinical trials that incorporate the expected sample size under the alternative hypothesis. Pharmaceutical Statistics 11(2), pp. 91-96. (10.1002/pst.501)
- Mander, A. P.et al. 2012. Weight loss in a commercial setting: Authors' reply. Lancet 379(9820), pp. 1003. (10.1016/S0140-6736(12)60425-5)
- Wason, J. M. S., Mander, A. P. and Thompson, S. G. 2012. Optimal multistage designs for randomised clinical trials with continuous outcomes. Statistics in Medicine 31(4), pp. 301-312. (10.1002/sim.4421)

### 2011

- Jebb, S. A.et al. 2011. Primary care referral to a commercial provider for weight loss treatment versus standard care: a randomised controlled trial. Lancet 378(9801), pp. 1485-1492. (10.1016/S0140-6736(11)61344-5)
- Thompson, S.et al. 2011. A proposed method of bias adjustment for meta-analyses of published observational studies. International Journal of Epidemiology 40(3), pp. 765-777. (10.1093/ije/dyq248)
- Wason, J. M. S., Mander, A. P. and Eisen, T. G. 2011. Reducing sample sizes in two stage phase II cancer trials by using continuous tumour shrinkage end-points. European Journal of Cancer 47(7), pp. 983-989. (10.1016/j.ejca.2010.12.007)
- Wilks, D. C.et al. 2011. Objectively measured physical activity and fat mass in children: A bias-adjusted meta-analysis of prospective studies. PLoS ONE 6(2), article number: e17205. (10.1371/journal.pone.0017205)
- Wilks, D. C.et al. 2011. Dietary energy density and adiposity: Employing bias adjustments in a meta-analysis of prospective studies. BMC Public Health 11, pp. -., article number: 48. (10.1186/1471-2458-11-48)

### 2010

- da Costa, T. H. M.et al. 2010. How much human milk do infants consume? Data from 12 countries using a standardized stable isotope methodology. Journal of Nutrition 140(12), pp. 2227-2232. (10.3945/jn.110.123489)
- Bluck, L. J. C.et al. 2010. Bayesian hierarchical methods to interpret the C-13-octanoic acid breath test for gastric emptying. Digestion 83(1-2), pp. 96-107. (10.1159/000316823)
- Mander, A. P. and Thompson, S. G. 2010. Two-stage designs optimal under the alternative hypothesis for phase II cancer clinical trials. Contemporary Clinical Trials 31(6), pp. 572-578. (10.1016/j.cct.2010.07.008)
- Cook, N.et al. 2010. A phase 2 study of vatalanib in metastatic melanoma patients. European Journal of Cancer 46(15), pp. 2671-2673. (10.1016/j.ejca.2010.07.014)
- Aston, L. M.et al. 2010. No difference in the 24-hour interstitial fluid glucose profile with modulations to the glycemic index of the diet. Nutrition 26(3), pp. 290-295. (10.1016/j.nut.2009.05.010)
- Aston, L. M.et al. 2010. No difference in the 24-hour interstitial fluid glucose profile with modulations to the glycemic index of the diet.. Nutrition 26(3), pp. 290-295. (10.1016/j.nut.2009.05.010)
- Siervo, M.et al. 2010. Acute effects of hyperglycaemia on asymmetric dimethylarginine (ADMA), adiponectin and inflammatory markers (IL-6, hs-CRP) in overweight and obese women with metabolic syndrome. British Journal of Biomedical Science 67(4), pp. 216-218. (10.1080/09674845.2010.11730322)

### 2009

- Sripanyakorn, S.et al. 2009. Moderate ingestion of alcohol is associated with acute ethanol-induced suppression of circulating CTX in a PTH-independent fashion. Journal of Bone and Mineral Research 24(8), pp. 1380-1388. (10.1359/JBMR.090222)
- Wilks, D. C.et al. 2009. Dietary energy density and weight gain: A bias-adjusted meta-analysis of prospective studies [Poster Abstract]. Obesity 17(S2), pp. S314. (10.1038/oby.2009.286)
- Prynne, C. J.et al. 2009. Diet and glycosylated haemoglobin in the 1946 British birth cohort. European Journal of Clinical Nutrition 63(9), pp. 1084-1090. (10.1038/ejcn.2009.43)
- Chatfield, M. and Mander, A. 2009. The Skillings-Mack test (Friedman test when there are missing data). Stata Journal 9(2), pp. 299-305. (10.1177/1536867X0900900208)

### 2008

- Cunnington, M.et al. 2008. Risk of ischaemic cardiovascular events from selective cyclooxygenase-2 inhibitors in osteoarthritis. Pharmacoepidemiology and Drug Safety 17(6), pp. 601-608. (10.1002/pds.1590)
- Johnson, L.et al. 2008. A prospective analysis of dietary energy density at age 5 and 7 years and fatness at 9 years among UK children. International Journal of Obesity 32(4), pp. 586-593. (10.1038/sj.ijo.0803746)
- Johnson, L.et al. 2008. Energy-dense, low-fiber, high-fat dietary pattern is associated with increased fatness in childhood. American Journal of Clinical Nutrition 87(4), pp. 846-854. (10.1093/ajcn/87.4.846)

### 2006

- Mander, A. P. and Bansal, A. 2006. Stepwise haplotype analysis: are LD patterns repeatable?. Human Genomics 2(6), article number: 376. (10.1186/1479-7364-2-6-376)

### 2002

- Henseik, A. E.et al. 2002. HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry 72(2), pp. 184-187. (10.1136/jnnp.72.2.184)
- Meyers, A.et al. 2002. INFORMATION REQUESTED Follow-up of replicated linkage results on chromosome 10: Putative role of the urokinase plasminogen activator gene in risk for late-onset Alzheimer's disease. Neurobiology of Aging 23(1), pp. S310.

My main research interest is in the design of clinical trials. I have worked in the area of developing novel adaptive trial designs for over 10 years and there has been a massive increase in their use. I really enjoy working on early phase trials because they are more readily improved using adaptive trials because there is a lot to explore whether this is finding the most appropriate dose, population or endpoint.

One of the largest projects I am involved in is the INNODIA consortium which started in 2015 www.innodia.eu and involved setting up an observational cohort of people newly diagnosed with type 1 diabetes (and their family members at risk) and latterly has transitioned to a platform trial with multiple sub-trials. The platform trial that is run under a master protocol that was given qualified advice by the EMA. and there are currently 4 sub-trials, the statistical trial work of two of the sub-trials is done within my team in Cardiff. There are plans for a fifth sub-trial that will be sponsored by Cardiff. It is exciting to see after 6 years that the trials have begun and it will be great to see the results coming over the next couple of years.

## Supervision

I am interested in supervising any student who wants to obtain a PhD in statistics and I have lots of ideas of potential research projects.

1. Adaptive platform trials

2. Biomarker stratified designs

3. Longitudinal group sequential trials