ISBN 978-5-4485-4016-5

      Created with Ridero smart publishing system

      List of Abbreviations

      AE – Adverse Event

      CRA – Clinical Research Associate

      CRO – Contract Research Organization

      CTMS – Clinical Trial Management System

      EDC – Electronic Data Capture

      EU – European Union

      FDA – Food and Drug Administration

      IXRS – Interactive Voice/Web Response System

      NA – North America (n)

      PM – Project Manager

      Introduction

      I am now hearing more and more often that Project Managers in Clinical Trials exist only to calculate the project money. This is not true: Project Managers do a lot of things in clinical trials and their primary role is definitely not to be a “calculator”.

      This is why I decided to write this book. It represents a summary of my experience and the most essential knowledge I have gained on this way. I tried to say that Project Management is first of all about its spirit and only to rather a limited degree – about money.

      This book is also to share my thoughts about clinical trials and project management. I hope that at least some of them will resonate with yours.

      I have tried to make the book an easy reading to the extent that is possible for this topic and not to bore you with overcomplicated schemes and diagrams. You will find only several simple tables added for the sake of illustration in the part devoted to goal setting.

      Philosophy of project management in clinical trials

      The axiom I use in my professional day-to-day life is that all principles of project management do apply to project management in clinical trials. No exceptions.

      Eventually every organization, even if it originally proceeded on the assumption that the usual, general project management has nothing to do with project management in clinical trials, turns to the ABCs of project management…

      But despite the fact that from the process point of view everything that has been created for project management in general applies to project management in clinical trials in particular, there is a huge gap between the two indeed. This gap is rather philosophical than anything else.

      Let’s have a look at the definition of a project: “Project – a temporary endeavor undertaken to create a unique product, services, or result.” (PMBOK Guide, 5^th edition, PMI, 2013). A positive, tangible, and lasting for some period of time result is meant in this definition. But a negative result is quite an acceptable result of a project in clinical trials and, what is more, it has a positive overall impact unlike a negative result of a project elsewhere.

      Imagine a project of constructing a bridge or building a space shuttle fails. What does that mean? Usually a disaster!

      But what if we have a look at an unsuccessful attempt to create a vaccine against a cancer, an antibiotic for an infectious disease treatment, or exon-skipping therapy for a rare genetic disorder treatment? They are very straightforward in telling the entire scientific society: “Do not go this way. We have been here and have been unsuccessful. Try another, your own way.”

      Each failed study is a step to development of effective and safe treatment of a disease or condition. For example, immunotherapy of cancer had been unsuccessful for decades until we got nivolumab and pembrolizumab. But these two look more like a miracle rather than a usual treatment now: millions of thanks to those who consecutively failed but never gave up.

      So if everything was done correctly and a clinical trial failure is supported by data of a high quality, that is fine. What is more, it is beneficial for the industry as a whole. The problem is that it is not always interpreted this way. And to explain why we need to consider two types of sponsors in clinical trials. I call them high-stake and low-stake ones.

      A typical representative of a high-stake sponsor is a small biotech company. Basically all they have is a molecule, which is a drug candidate. Just candidate – they have nothing to sell on the market yet. Consecutively, they do not have their own money: they are constantly trying to find investors. To attract money this way they promise that some milestones – first regulatory approval of the study, first patient in, last patient in, database lock – will be met on time. And that is one of the first things for a CRO PM to learn about their high-stake sponsor – what their internal milestones are.

      In addition to shortage of money high-stake sponsors normally have shortage of everything else – human resources, experience, processes and procedures, IT infrastructure… The US Food and Drug Administration even has a special program to support such sponsors – small businesses, as they call them.

      And please add a high turnover rate to all these factors. As a result, such companies do not have what I call corporate memory. In the middle of a trial they do not know what key decisions have been made by them themselves or their predecessors and are very often prone to challenge them, which is not always a good idea in an ongoing trial.

      They are constantly overloaded and distracted. It is hard for them to observe timelines for study-related documents like plans, budgets, and so on. One of the most frequent requests you can hear from them begins with the words “Could you please re-send?..” – an e-mail, a document, and so on.

      To realize the real pressure they are under and to respect these people and what they do are real keys to building successful working relationship with them for a CRO manager rather than to discuss kids and pets as normally recommended by books devoted to business communication…

      And since the stake is that high and pressure is incredible for such sponsors, negative trial results may drive a strong emotional reaction in such a sponsor, which is absolutely understandable.

      There was a phase III oncology study for a high-stake client where Progression Free Survival was the primary endpoint. That double-blind trial comprised two groups – the control group was administered the standard of care regimen, and the main group – standard of care regimen plus the novel agent. After the database lock and statistical analysis it turned out that there was no difference in Progression Free Survival between the two groups. Literally, their curves simply coincided.

      It was a kind of shock for the sponsor, although, to be honest, 85% of all phase III trials fail, and it is not secret to anyone. Such general information does not help much in a concrete situation. The CRO was suspected of enrolling not right patients. It was a bit weird accusation, because each and every subject on the study had been approved by the sponsor Chief Medical Officer. In the end the sponsor requested to exclude some patients from analysis. Those subjects were not treated heavily enough before inclusion into the trial according to the sponsor’s idea.

      After several rounds of discussion those “not treated heavily enough prior to study patients” were excluded from analysis. It resulted in one interesting thing. The curves continued coinciding in exactly the same way. If the drug works, it works. If it does not, it does not, and nothing can be done about it.

      The other type of sponsor is low-stake ones. A typical representative is a pharmaceutical giant. They also have a lot of internal pressure: milestones, financial reports, and so on. It is also important to understand from the very beginning what your counterpart’s pain is. But the key differences are they already have registered product (s) to sell and to have money from and each molecule they develop is normally not the only one. They do have a pipeline. And if a given molecule fails in a given indication, it is painful, but it is not a tragedy.

      I have