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Papademetris X., Quraishi A.N., and Licholai G.P.

Introduction to Medical Software: Foundations for Digital Health, Devices and Diagnostics.

Cambridge University Press (2022). ISBN 9781316514993.

See also the official page at the webpage of Cambridge University Press.

The book is also available from Amazon.

The table of contents of the book and the first chapter are available here.

Blog Posts and Other "Press"

For Instructors

You will be able register for a Cambridge University Press Higher Education account to request access to instructor resources for the book.

About the cover of the book

In this video segment, we explain the choice of the cover of the book. Medical software lies at the intersection of diverse fields such as medicine, law, business, computer science and engineering each of which is represented by one of the petals of the flower on the cover.

Chapter Abstracts

1. Introduction to Medical Software

This chapter begins by defining what medical software is and what makes it unique and describing the regulatory process that governs it (Section 1.1), including a brief introduction to industry standards. Following this, we discuss the constraints (both business and technical) placed on the software process by the medical environment (Section 1.2). The chapter concludes with a discussion of the challenges that result from the use of artificial intelligence/machine learning (AI/ML) techniques (Section 1.3). This section also provides references to other parts of this book where we discuss AI/ML issues.

2. The FDA and Software

This chapter describes the regulatory process for medical software, with a particular emphasis on the documents issued by the United States Food and Drug Administration (FDA). We first describe the FDA itself (Section 2.1), including a brief history of how the current process has evolved over the past century. We then review in detail some key FDA regulatory documents (Section 2.2) and provide an overview of the actual regulatory process (Section 2.3). After this, we survey related documents and agencies from the rest of the world (Section 2.4). Unsurprisingly, given that most regulatory agencies are participants in the International Medical Device Regulators Forum (IMDRF), there is significant convergence in the regulations operating in different countries. The next section (Section 2.5) discusses the implications of these regulations for the software process. The chapter concludes with a look at emerging regulatory guidance on the use of artificial intelligence/machine learning (AI/ML) techniques in medical software and some comments about the applicability of some of the concepts in the medical software regulations to other industries (Section 2.6).

3. Operating within a Healthcare System

This chapter provides background on the constraints imposed on software by the need to operate within a healthcare environment. We first present an overview of the environment and the constraints under which our software must operate (Section 3.1). A description of the current healthcare environment (Section 3.2) follows. We begin with a description of the complex system currently in place in the United States, and then discuss how healthcare operates in the rest of the world. The next section discusses clinical information technology (Section 3.3), with an emphasis on electronic health records (EHR) and imaging databases (PACS). Following this, we review issues related to data privacy (HIPAA and GDPR) in Section 3.4. We conclude this chapter with a discussion of Cybersecurity (Section 3.5.) This is one of the primary sources of security concerns in medical software and a topic of increasing importance in today's connected world.

4. Quality Management Systems

This chapter provides an overview of quality management systems (QMS). There is an increasing emphasis of regulators on the `organization' as opposed to the `product,' which places an even greater emphasis on the use of a QMS. We first introduce what a QMS is (Section 4.1) and provide some regulatory background, including a discussion of the recent FDA precertification program. Next we discuss various international standards that apply (Section 4.2). The core of this chapter is an extended discussion of the IMDRF QMS regulatory document (Section 4.3), which provides an excellent and SaMD-specific description of this important topic. The chapter concludes with a brief discussion (Section 4.4) of the implications of quality systems (or rather their absence) on research and scientific software and how failure to have/adhere to a QMS (Section 4.5) can lead to serious problems.

5. Risk Management

This chapter presents an introduction to risk management, a core regulatory requirement for all medical software. We begin with an overview of the regulatory background (Section 5.1) and then review both the international standard ISO 14971:2019 and a recent guidance document from the IMDRF. Next we describe the process of risk analysis (Section 5.2), including issues related to the use of artificial intelligence/machine learning techniques. We then discuss risk evaluation (Section 5.3) and risk control strategies (Section 5.4). The chapter concludes with a section (Section 5.5) that briefly outline the role of risk management in the software life cycle process described in Part III of this book, where risk management will be our ever-present companion.

6. Taking an Idea to Market: Understanding the Product Journey

This chapter presents the `business' view of medical software. It takes a company to bring an idea to market and, ultimately, clinical use. We begin with a brief description of issues related to entrepreneurship (Section 6.1): should somebody who has a promising idea consider starting a company on their own? Next, we discuss the issues of user-centered design (Section 6.2) and of articulating the value proposition of a new product (Section 6.3). We then take a detour through the minefield that is ensuring proper intellectual property protections (Section 6.4). Finally, we discuss the process of raising capital to support a new venture (Section 6.5). While the material in this chapter is focused on startups, it is also important for those that are employed in `large' companies, as this material will give them an understanding of what their `managers' are worrying about. In a large company, the capital raising and marketing may happen internally as a particular group within a company tries to obtain support for a new product from higher level management. The process looks different, but the fundamental concepts are just as applicable. The same concepts also apply to university research.

7. Medical Software Applications and Growth Drivers

This chapter presents an overview of current medical software applications and the factors that promise to drive growth in this area. We begin this chapter by defining and discussing some important terms such as Digital Biomarkers and Digital Health (Section 7.1). Next, we describe the current technological transformation of healthcare (Section 7.2). In Section 7.3, we present the major challenges faced by the healthcare sector and in particular the triple aim of improving patient experience (better care), improving the health of the population (better quality) and reducing the cost of care (better value). Section 7.4 discusses the promising opportunities that will be become available as new technologies are adopted in healthcare and Sections 7.5--7.10 discuss the drivers of the current wave of healthcare technology growth, including financing, innovations by the Food and Drug Administration (FDA), and increased collaboration across the healthcare continuum. The promises of this technological transformation of healthcare are examined in clinical care, digital medicine, research & development, and remote monitoring. We conclude the chapter with some recommendations for software developers entering this field (Section 7.11)

8. Mathematical Background

Much of the work involved in the development of medical software (and in particular the process of software validation) depend critically on an understanding of topics such as probability theory, statistics and increasingly machine learning. The goal of this chapter is to provide students with some theoretical grounding in this general area. After a brief high-level introduction to decision theory (Section 8.1), we discuss each topic in turn, beginning with an introduction to probability (Section 8.2) and statistics (Section 8.3), including an extended discussion of the topic of signal detection, which is particularly important in medical applications. We then present an overview of machine learning and some of the issues involved in the use of these techniques (Section 8.4). Next, we introduce the concept of statistical significance (Section 8.5) and conclude the chapter with a discussion of the importance of randomization (Section 8.6) in clinical studies.

9. Topics in Software Engineering

This chapter provides some basic background on selected topics in software engineering. This should be useful for those readers whose background is primarily in basic science and engineering, who may have not been previously exposed to this type of material. This chapter is meant to complement the introduction to mathematical topics presented in Chapter 8. We begin with a brief overview of software engineering (Section 9.1). Next, we discuss the software life cycle (Section 9.2), the organizing foundation of any software project. Following this, we present issues related to the use of artificial intelligence/machine learning (AI/ML) techniques (Section 9.3) in software, in particular the centrality of data in this process. Next, we discuss modern computing environments such as cloud-based infrastructures and mobile devices (Section 9.4). The chapter concludes with a description of two core software engineering topics: software testing (Section 9.5) and source code management (Section 9.6).

10. The Overall Process

This chapter presents an example medical software life cycle process. We first introduce the topic (Section 10.1), and introduce our example project -- the image-guided neuro-navigation system -- that we will use to illustrate the process over the next few chapters. Next we summarize our life cycle `recipe' (Section 10.3) for medical software. This recipe follows the guidelines in the international standard IEC 62304. It begins with identifying user needs and concludes with the satisfaction of these needs via a structured process of first establishing requirements and then designing, implementing, testing and releasing our software. We also briefly discuss software safety classifications (Section 10.4) and present some thoughts on traceability and planning for the overall process (Section 10.5). The chapter concludes with a section that uses the children's game `Telephone' to illustrate some of the potential pitfalls in this long process (Section 10.5.4).

11. Identifying User Needs

This chapter discusses the processes of identifying the needs of our users which is the first step in the software life cycle. We begin with an overview of the structure of creating new projects. Next, we apply the "Brown Cow" model (Section 11.1) as a guide for how to go about understanding the user's current situation and future needs. We will then touch on the formal process for creating a Use Specification as discussed in the guidance document IEC 62366-2 (Section 11.2). Finally, we `begin' our example image-guided neuro-navigation project (Section 11.3) and use this to illustrate the concepts presented in this chapter. We will return to this project in the next few chapters as we continue along our software life cycle journey.

12. The System Requirements Specification

This chapter describes the process of creating a systems requirements document which is one of the most important steps in the software life cycle. First, we orient ourselves as to our position in this life cycle (Section 12.1). Next, we present a brief review of key regulatory issues (Section 12.2), and following this we describe a template for creating this document (Section 12.3). Next, we discuss in more detail the process of writing a requirement (Section 12.4). As always, we then revisit risk management (Section 12.5) and address how to evaluate our requirements for potential harms. The next section (Section 12.6) discusses how to review systems requirements. The chapter concludes by continuing our discussion of the example image-guided neuro-navigation project by presenting an outline of what the systems requirements document for this might look like (Section 12.7).

13. The Software Design Document

This chapter describes the software design document. This is the first step in the software life cycle where we leave the abstract plane and begin to think more concretely about the product. The structure of this chapter is as follows. First, we discuss (Section 13.1) that we are at the point of creating a bridge from the system requirements to the actual code. Next, we present a brief review of key regulatory issues (Section 13.2) involved in creating this document. We then describe a template for the software design document (Section 13.3). As always, we then revisit risk management (Section 13.4) and address how to evaluate our design for potential harms. Within risk management we address the important issue of human factors. The chapter concludes (Section 13.6) by continuing our discussion of the example image-guided neuro-navigation project by presenting an outline of what the software design document for this might look like.

14. Software Construction and Testing and Verification

This chapter describes software construction and testing. These are the very concrete steps in the software life cycle (Section 14.1). Next we discuss `construction,' or coding (Section 14.2) beginning with a brief review of key regulatory issues. We follow this with a presentation of programming topics and conclude this section with an extended discussion of risk management in the context of the programming process. The next section (Section 14.3) focuses on testing and again begins with a review of regulatory issues before moving to brief section on risk management in the context of testing. In the final section (Section 14.4), we provide some pointers as to how one would go about creating a verification plan.

15. Software Validation

This chapter describes the process of software validation. We first begin with a brief overview of what validation is. We then review the regulatory guidance for validation (Section 15.1) in general, and then provide an extended discussion on the issues that affect the validation of software modules that use artificial intelligence/machine learning techniques in particular. Next, we present a description of human subject studies and clinical trials (Section 15.2), including a description of the necessary ethical constraints on such studies. In the last part of this chapter (Section 15.3), we present a simplified strategy for designing a validation plan appropriate for an introductory class.

16. Deployment, Maintenance and Decommissioning

In this short chapter, we discuss the final three steps in the software life cycle: (i) deployment (Section 16.1), (ii) maintenance (Section 16.2), and (iii) decommissioning (Section 16.3). These are complex topics in their own right. Our goal here is, to simply and briefly, highlight some information about each of these processes so as to make the reader aware of what the major issues are for the sake of completeness.

17. [Vignette] Therac 25: Software that Killed

This vignette describes the Therac-25 radiation therapy machine, whose software bugs and lack of hardware safety interlocks led to six serious accidents from 1982-1987. Three lives were claimed due to overconfidence in software and loose design regulations. Ultimately, these events were a catalyst for the FDA to begin investigating and regulating medical software.

18. [Vignette] Mars Climate Orbiter: Lost Without A Trace

This vignette describes the accidental destruction of a multi-million-dollar outer space satellite, primarily due to inconsistency of mathematical units used in different components of the system. Poor fault analysis, decision-making, integration testing, and auditing led the Mars Climate Orbiter to burn up in Mars' atmosphere, never to be contacted again.

19. [Vignette] The Failed Launch of a Critical Webpage

This vignette discusses the failed launch of the online marketplace for purchasing individual healthcare insurance that was created as part of the Affordable Care Act (ACA) in Fall 2013. A key component of this effort was the webpage (, through which individuals would be able to buy health insurance. The launch of this webpage failed, resulting in significant problems in the implementation of the ACA. This was a major process failure: software best practices were not followed, resulting in major cost overruns.

20. [Vignette] The 2020 Iowa Caucus App: An Unreliable App that Caused National Embarrassment

On Monday, February 3rd, 2020, the results of the Democratic Iowa Caucus, the first caucus in the U.S. election cycle, were delayed as a result of bugs in the software used to report the results. This software (the IowaReporter App) was not properly tested prior to the elections, and the whole reporting system failed during the event. This led to multi-day delays in reporting the results of the caucus, throwing the entire primary election process into confusion and disarray.

21. [Vignette] The Boeing 737-MAX Disasters: Using Software to Fix Hardware Problems

In the case of the Boeing 737 MAX disaster, the manufacturer tried to address hardware problems with software fixes in order to avoid the costs of re-certification of what would have been a new airplane (had the fixes been done in hardware). Overconfidence in the software and insufficient testing and pilot training led to two fatal crashes and 346 fatalities. Boeing has already paid a substantial fine to settle some of the legal issues arising from the case, though other legal procedures are still ongoing.

22. [Vignette] The Averted Y2K Crisis: Successful Crisis and Risk Management

The changeover from 1999 to 2000 introduced a major risk of system failure in computer systems worldwide. This had to do with older software's use of 2-digit numbers to store the year. As the year (in two digits) moved from 99 to 00, there were serious possibilities of many systems failing. This resulted in a major effort to fix this problem across multiple major computer systems. In the end, despite minor issues, the change to the new millennium happened without any major problems.


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