Bill Cochran: His Contributions to Medicine and Public Health and Some Personal Recollections

There is a tremendous need in our technological society to train statisticians for all sectors of education, government, and industry. Because statistical training has largely been restricted to graduate schools, the profession is losing many good students to other fields of study. Members of the statistics community are encouraged to reach out to high-school students and undergraduate students to increase the awareness of statistics as a scientific field of study and as a professional career. The ASA Council of Chapters has recently completed a slide presentation entitled “Statistical Science: The Profession,” which was professionally developed to aid this endeavor. In addition, high-school teachers, high-school counselors, and professors of mathematics and science education are identified as important audiences for hearing this message and for broadening general public awareness of what our profession has to offer.     

Visualising interaction effects

In drug discovery, statisticians often work with biologists and chemists to uncover relationships between the various chemical properties and the biological effects of compounds. The aim is to "design" drugs that have exactly the desired pharmaceutical effects. Phil Woodward and Mark Whitlock of Pfizer Global R&D show how a graph can uncover deeply hidden relationships and guide chemists in their efforts to find the next blockbuster drug.     

Statisticians in European regulatory agencies

The UK body of statisticians in the pharmaceutical industry, PSI, has called on heads of European regulatory agencies responsible for assessing applications for marketing authorizations for new medicines in the EU to employ full time statisticians. In order to assess the present situation a survey has been conducted to identify the number of agencies employing one or more full time statisticians. Out of 29 responding agencies, 12 employed one or more statisticians on a full time basis, whereas 17 did not. Among these 17, 7 involved external experts on a regular basis, 5 involved external statisticians on a case‐by‐case basis, whereas 5 never involved external statistical expertise. Failure to involve statisticians in the assessment of efficacy and safety of medicines does not automatically lead to reports of low quality or invalid assessment of benefit‐risk. However, in depth knowledge of statistical methodology is often necessary to uncover weaknesses and potentially biased efficacy estimates. This might be of importance for the final opinion on granting a marketing authorization, and statistical review should therefore be conducted by those who are professionally expert in the area. A positive trend toward an increased involvement of statistical expertise in the European network of regulatory agencies is observed. Copyright © 2009 John Wiley & Sons, Ltd.     

Do statisticians count? A personal view

The number of statisticians working in the pharmaceutical industry has risen 50‐fold since the formation of PSI in 1977. It would be comforting to think that the influence of statisticians within their companies has increased in a parallel fashion, however I do not believe that to be the case. In this paper I look at barriers which prevent statisticians contributing as much as they should and look at potentials solutions. Copyright © 2002 John Wiley & Sons, Ltd.     

Re-Defining the Who,When, and Where of Mentoring for Professional Statisticians

Organizations tailor their mentoring strategies to accommodate internal resources and preferences, producing different approaches in academic, government, and corporate environments. Across these settings, three common barriers impede effective mentoring of statisticians: overspecialization, time constraints, and geographic dispersion. The authors share mentoring strategies that have emerged at their organization, Mathematica Policy Research, to overcome these obstacles. Practices include creating a methodology working group to unite researchers with diverse backgrounds, integrating mentoring into existing workflows, and harnessing modern technological infrastructure to facilitate virtual mentoring. Although these strategies emerged within a specific professional context, they suggest opportunities for statisticians to expand the channels through which mentorship can occur.     

A rich opportunity

Certain sectors are well known for employing large numbers of statisticians, points out David Hand. These include the pharmaceutical sector, medical research and government. Less well known, however, is that the personal . Financial services sector also requires large numbers of numerate people, and that statisticians, with their understanding of risk and uncertainty and their ability to extract information from large quantities of data, are in particular demand.     

Issues in applying recent CPMP ‘Points to Consider’ and FDA guidance documents with biostatistical implications

The International Conference on Harmonisation guideline ‘Statistical Principles for Clinical Trials’ was adopted by the Committee for Proprietary Medicinal Products (CPMP) in March 1998, and consequently is operational in Europe. Since then more detailed guidance on selected topics has been issued by the CPMP in the form of ‘Points to Consider’ documents. The intent of these was to give guidance particularly to non‐statistical reviewers within regulatory authorities, although of course they also provide a good source of information for pharmaceutical industry statisticians. In addition, the Food and Drug Administration has recently issued a draft guideline on data monitoring committees. In November 2002 a one‐day discussion forum was held in London by Statisticians in the Pharmaceutical Industry (PSI). The aim of the meeting was to discuss how statisticians were responding to some of the issues covered in these new guidelines, and to document consensus views where they existed. The forum was attended by industry, academic and regulatory statisticians. This paper outlines the questions raised, resulting discussions and consensus views reached. It is clear from the guidelines and discussions at the workshop that the statistical analysis strategy must be planned during the design phase of a clinical trial and carefully documented. Once the study is complete the analysis strategy should be thoughtfully executed and the findings reported. Copyright © 2003 John Wiley & Sons, Ltd.     

Modelling and simulation in the pharmaceutical industry--some reflections

Modelling and simulation (M&S) is increasingly being applied in (clinical) drug development. It provides an opportune area for the community of pharmaceutical statisticians to pursue. In this article, we highlight useful principles behind the application of M&S. We claim that M&S should be focussed on decisions, tailored to its purpose and based in applied sciences, not relying entirely on data-driven statistical analysis. Further, M&S should be a continuous process making use of diverse information sources and applying Bayesian and frequentist methodology, as appropriate. In addition to forming a basis for analysing decision options, M&S provides a framework that can facilitate communication between stakeholders. Besides the discussion on modelling philosophy, we also describe how standard simulation practice can be ineffective and how simulation efficiency can often be greatly improved.     

Bioinformatics: new science–new statistics?

The new research field of bioinformatics is concerned with the collection, maintenance and processing of genomic information. Like statistical genetics, it provides computational techniques for unravelling the complex machinery of the genome, but it is distinct in emphasis and approach. As a relative newcomer to bioinformatics, statistician Wally Gilks sets out to convey his excitement about the subject and to explain the opportunities it presents to professional statisticians.     

The statistician and the computer

This paper reviews the impact of the computer on the analysis and interpretation of data. It suggests the need for professonal statisticians to recognize that almost all future analysis of data will be carried out by non-statisticians with the aid of statistical program packages. Therefore, the emphasis of statistical training for scientists, engineers, administrators and decision-makers should be on the design of data collection and the choice of appropriate methods of analysis. Both in the teaching of statistics and in the development of computer programs for statistical analysis there are important and urgent tasks to be addressed by professional statisticians.     

The professionalization of the 'shoe clerk'

Summary.  The address reviews the professionalization of statisticians working in the regulated world of drug development. The need for statisticians to continue to push the boundaries of their professional environment is stressed. It is argued that to maintain the strength and influence of the profession it is neither desirable, nor necessary, to define in a statutory sense access to the profession.     

Subgroup analyses of clinical effectiveness to support health technology assessments

Subgroup analysis is an integral part of access and reimbursement dossiers, in particular health technology assessment (HTA), and their HTA recommendations are often limited to subpopulations. HTA recommendations for subpopulations are not always clear and without controversies. In this paper, we review several HTA guidelines regarding subgroup analyses. We describe good statistical principles for subgroup analyses of clinical effectiveness to support HTAs and include case examples where HTA recommendations were given to subpopulations only. Unlike regulatory submissions, pharmaceutical statisticians in most companies have had limited involvement in the planning, design and preparation of HTA/payers submissions. We hope to change this by highlighting how pharmaceutical statisticians should contribute to payers' submissions. This includes early engagement in reimbursement strategy discussions to influence the design, analysis and interpretation of phase III randomized clinical trials as well as meta-analyses/network meta-analyses. The focus on this paper is on subgroup analyses relating to clinical effectiveness as we believe this is the first key step of statistical involvement and influence in the preparation of HTA and reimbursement submissions.     

Who wants to be an ICH Euro billionaire?

The ICH E9 guideline on Statistical Principles for Clinical Trials is a pivotal document for statisticians in clinical research in the pharmaceutical industry guiding, as it does, statistical aspects of the planning, conduct and analysis of regulatory clinical trials. New statisticians joining the industry require a thorough and lasting understanding of the 39-page guideline. Given the amount of detail to be covered, traditional (lecture-style) training methods are largely ineffective. Directed reading, perhaps in groups, may be a helpful approach, especially if experienced staff are involved in the discussions. However, as in many training scenarios, exercise-based training is often the most effective approach to learning. In this paper, we describe several variants of a training module in ICH E9 for new statisticians, combining directed reading with a game-based exercise, which have proved to be highly effective and enjoyable for course participants.     

It shouldn't happen to a statistician

Helen Clough and Patrick Brown are statisticians working in a cross-disciplinary veterinary epidemiology collaboration, uniting statisticians, mathematical modellers, veterinarians, molecular biologists and microbiologists. They describe the strengths that statisticians bring to the collaboration and the creative tensions that arise when both statistical and mathematical modelling techniques are used.     

Some perspectives on statistical computing

The author argues for an increased emphasis on computing in the training of statisticians and in their professional practice. He describes some of the current technological challenges and demonstrates the importance for statisticians of becoming more active in computational aspects of their work and specifically in producing software for carrying out statistical procedures. Such a reorientation will require substantial changes in thinking, pedagogy and infrastructure; the author mentions some of the conditions required to achieve these goals.     

Looking Forward into the 1980's: A Personal View of the Problems and Prospects for the Statistical Profession

The paper begins with a discussion of the state of research and development in Australia, and the effect of technological change, and then provides an assessment of consequent Government policy on the funding of research and development and of tertiary educational institutions. This is then related to likely consequences for the statistical profession. Various issues facing the Statistical Society and statisticians in general are discussed. These include public responsibility in the face of scepticism resulting from widespread statistical misrepresentation, employment opportunities for graduates, the relationships between theoreticians and practitioners, and the state of the statistical literature.     

A course in constructing effective displays of data for pharmaceutical research personnel

Interpreting data and communicating effectively through graphs and tables are requisite skills for statisticians and non‐statisticians in the pharmaceutical industry. However, the quality of visual displays of data in the medical and pharmaceutical literature and at scientific conferences is severely lacking. We describe an interactive, workshop‐driven, 2‐day short course that we constructed for pharmaceutical research personnel to learn these skills. The examples in the course and the workshop datasets source from our professional experiences, the scientific literature, and the mass media. During the course, the participants are exposed to and gain hands‐on experience with the principles of visual and graphical perception, design, and construction of both graphic and tabular displays of quantitative and qualitative information. After completing the course, with a critical eye, the participants are able to construct, revise, critique, and interpret graphic and tabular displays according to an extensive set of guidelines. Copyright © 2013 John Wiley & Sons, Ltd.     

A proposal for a new PhD level curriculum on quantitative methods for drug development

This paper provides an overview of “Improving Design, Evaluation and Analysis of early drug development Studies” (IDEAS), a European Commission–funded network bringing together leading academic institutions and small‐ to large‐sized pharmaceutical companies to train a cohort of graduate‐level medical statisticians. The network is composed of a diverse mix of public and private sector partners spread across Europe, which will host 14 early‐stage researchers for 36 months. IDEAS training activities are composed of a well‐rounded mixture of specialist methodological components and generic transferable skills. Particular attention is paid to fostering collaborations between researchers and supervisors, which span academia and the private sector. Within this paper, we review existing medical statistics programmes (MSc and PhD) and highlight the training they provide on skills relevant to drug development. Motivated by this review and our experiences with the IDEAS project, we propose a concept for a joint, harmonised European PhD programme to train statisticians in quantitative methods for drug development.     

网络技术下统计的变革和统计教育面临的任务

网络经济的发展使现行的统计信息生产方式和统计制度发生深刻变革,使统计人才的知识结构发生重大变化,从而对统计教育的着力点和培养目标、培养方式提出了新的要求。如何培养大量优秀的复合型统计人才,极大地提高统计人员的素质,是统计教育面临的艰巨任务。     

The potential for bias in reporting of industry-sponsored clinical trials

Concerns about potentially misleading reporting of pharmaceutical industry research have surfaced many times. The potential for duality (and thereby conflict) of interest is only too clear when you consider the sums of money required for the discovery, development and commercialization of new medicines. As the ability of major, mid-size and small pharmaceutical companies to innovate has waned, as evidenced by the seemingly relentless decline in the numbers of new medicines approved by Food and Drug Administration and European Medicines Agency year-on-year, not only has the cost per new approved medicine risen: so too has the public and media concern about the extent to which the pharmaceutical industry is open and honest about the efficacy, safety and quality of the drugs we manufacture and sell. In 2005 an Editorial in Journal of the American Medical Association made clear that, so great was their concern about misleading reporting of industry-sponsored studies, henceforth no article would be published that was not also guaranteed by independent statistical analysis. We examine the precursors to this Editorial, as well as its immediate and lasting effects for statisticians, for the manner in which statistical analysis is carried out, and for the industry more generally.