Olympian projects require world-class planning
pharmafile | April 14, 2008 | Feature | Research and Development |Â Â clinical trials, project planningÂ
The latest edition of the CMR International R&D Factbook shows that the mean time from protocol approval to final report sign-off has remained at 25.4 months for the three years from 2002 to 2005. Clinical development's position as the largest cost centre has also remained, soaking up 34% of total R&D expenditure. This might be tolerable if we were improving success rates, but CMR says these are still low. Only 12% of new active substances entering first-in-man studies reach the market, and only 20% of those entering phase II achieve this.
So why hasn't the industry been able to devise project management techniques to tackle these problems?
Over the last 20 years or so drug companies have imported project management practices from areas such as engineering, construction and software development, some of them very well established. The famous Gantt chart was devised during World War One, and network analysis, usually termed PERT (Project Evaluation and Review Technique) appeared in the 1950s. With drug development such a newcomer to this discipline, it is not surprising that project management is still maturing in most organisations. My view is that it has been unusually slow to mature, when so much of the development of techniques has already been done by other industries, and I want to examine some of the reasons for this.
Some will argue that fully mature project management won't improve the success rate for drugs entering phase I, because that is determined by the properties of the drug, but I beg to differ a little. Most would agree that better management can accelerate approval, whatever the drug is. The benefit of even a few days' earlier market launch is measured in millions of dollars, which means that modest improvement targets will pay for the effort of their implementation many times over. We need not aim to halve our project durations. An improvement of 10% is typically seen after full rollout of a project management methodology within an organisation, which equates to two months earlier completion of a trial on average. That doesn't sound a lot, but what if you could do that for all your drug development? You would be a year earlier to market, and in a competitive situation, getting ahead of your rivals is worth more than simply the extra year's sales. It could put you in a dominant position.
I am not saying that we are not doing project management at all in clinical trials. But in my 34 years in this industry I have not seen a single company doing it as rigorously as I know it is done in other industries. Don't simply take my word for that. As most readers will know, the regulatory authorities are escalating their programmes of Good Clinical Practice (GCP) inspections. In the UK, the MHRA for one identifies project management as a particularly common weakness. I have formed the strong impression that the reason for this is largely cultural. Before I analyse that, let's look at two aspects of clinical trials that I'll admit do make project management challenging.
Escalating complexity
Someone once told me that a clinical trial is so complex and unpredictable that detailed planning is not a practical proposition. Yes, complexity has increased hugely, especially with the globalisation of studies. We are faced with highly variable practices and regulatory requirements among the countries we are using, compounded with continual changes over time. Quite often, by the time we have planned what we want to do, something has changed somewhere. But this isn't an excuse not to do the planning. Because if we don't start with a plan, it's going to be far more difficult to detect when things are going wrong and do something about it.
Adding to this complexity is the need to buy in more services, which means dealing usually with multiple vendors. There can often be regulatory reasons for this – for example, the FDA no longer accepts paper-based patient diaries for primary efficacy data and requires electronic ones. Should we have to set up project plans for everything the vendors are doing? How can we do this unless we know their business as well as they do?
Increased regulation
Few readers will be unaware of the EU Clinical Trials and GCP Directives, transposed recently into UK law. It's worth remembering however that the EU legislation is just Europe's take on GCP as defined by the International Conference on Harmonisation (ICH), so the basic requirements are much broader geographically than Europe. Indeed ICH GCP is followed in more regions than just the official ones of North America, Europe and Japan. So wherever we are operating these days we are likely to face a lot more regulation than 10 years ago. The UK now has additional layers of approval, such as local R&D committees, and if we are using certain special techniques, such as radio-labelled materials or gene therapies, we need approval from appropriate regulatory bodies. All these components will have to be assembled into an effective project plan.
This is all enough to put anyone off, isn't it? But challenging as these constraints are, they are surmountable with enough effort and knowledge. Planning software is quite capable of modelling highly complex projects, and handling change over time. The techniques are very well honed in other industries.
And if you think your phase III programme is complex, try planning the London 2012 Olympiad. As I have said, the problem is more a cultural one. It centres on the project manager. If you look at the box opposite, you will see a brief profile of what a project manager is and does. And when you next get the chance, have a look at the job adverts in a decent newspaper for project managers in, say, civil engineering or oil exploration. You might at first be surprised at how attractive some of the salaries are, but you should focus more on responsibility, authority and sizes of budgets to control. These project managers have more clout than their peers in pharmaceuticals do.
Yet there are other clear differences. Firstly, non-pharma project managers don't need such a high level of academic qualification. I know things are changing, but I still come across companies that insist on PhDs to do this job. The subject of the PhD seems to be immaterial – you just have to have one. There are PhD engineers of course, but they are not de rigueur in project management.
Other industries usually demand a formal qualification in project management itself. This might be, at a minimum, a professional membership, then a certification (such as Project Management Professional, or PRINCE2 Practitioner), or even a first degree or masters in the discipline. Compare this with drug companies. Yes, they are beginning to see the value of proper project management knowledge, but it's not common. Now I know many very good project managers in drug development who don't have formal project management qualifications, but my point is really about perception. It seems clear that a high level of skill in this field is not demanded because the need for it isn't recognised at senior levels. Project management is a kind of pharmaceutical Cinderella.
Why should this be? I think it's because of a general lack of understanding and willingness to understand what projects are, and how they work. Most companies in our industry are in my experience dominated more by line management than by the needs of the project.
Matrix management
The conflict between the two even has a name – matrix management. This is often bandied about as a solution to a problem, but it's not, it's just the name for the problem. The matrix is comprised of the lines of reporting for projects and the standing hierarchy crossing each other. These become confused when people don't think analytically about the rules that define the interfaces between projects and functional departments. This highlights a key concept that I think is often not appreciated. Management is commonly separated into 'hard' and 'soft' skills. The former are the analytical and mechanistic skills, and the latter the people-related ones. I think this separation is artificial. In the case of matrix management, the conflicts arise between people, because they have not analysed the situation and planned accordingly. If they map out how things will work, people understand and comply more easily. The same applies to the project time plan itself. A fully developed plan includes not just the time targets, but what is being delivered by each task, who will deliver it, who checks it, what it costs, etc. It displays what everyone has agreed to do. It is not produced by one person sitting with a computer and playing with dates, it is a collaborative exercise which involves the whole team.
We should ask ourselves why the culture in many pharmaceutical companies is like this. It's extremely common to see a weakness in project oversight. The established PRINCE2 methodology (see box) defines the organisation of the project, with the project directorate at the top, and the project manager reporting to that body. The directorate is there to sponsor the project, to solve problems when the manager needs help (which should be rarely), and to give approvals for major stages of the project (not detailed stages). In practice I've never seen this fully put into effect in clinical trials. I have seen a rough approximation specified in a contract, as a steering committee, but it wasn't set up. This is a major omission, because the huge complexity of clinical trials these days means everyone is continually focusing on detail, and usually fighting fires, while not much attention is paid to the bigger picture. So, if the problem is lack of top level oversight, and thus lack of support for project management as a discipline, why the lack of willingness to conduct oversight? Well, I didn't promise I had the answer to that!
Planning: the foundation stone
I'll turn now from organisation to planning, although similar principles apply. A few years ago I turned up as an interim project manager at a well-established company, and learned I had three months to set up a pivotal study. One of the many lessons from other industries is the time they devote to planning – typically twice as much as we do. Planning is the foundation stone of the project, but it is given much less time and resource than it needs. Planning is commonly thought to consist of sitting at the computer and playing with dates. It actually starts well before that, when we define what we want to do. In the 20 odd years I've been training in project management, defining the project is the technique people find hardest to understand. Essentially it consists of agreeing the functional requirements, finding practical solutions to those requirements, and breaking down those solutions to a set of tasks – and most importantly deliverables. It goes wrong if the functional requirements are wrong or unclear, so time spent on discussing these is well spent. I mentioned earlier the success rates for compounds at various stages of clinical development, and clearly whether we achieve success depends on what targets we define. This means getting the target product profile right. Maybe it's a trade off – should we have a marketable product with a slightly degraded profile, or should we set the bar high and increase the risk of failure? Whatever we decide, we need to spend time on getting the right decision.
Box: What is project management?
A project is anything that delivers a result, and which has a beginning, middle and end. Therefore the famous Eden Project is not a project at all – only building it was. Classically three types of target are recognised, which are time, cost and deliverables (products). The project manager is the person appointed to plan and deliver the outcome of the project. They interact with project stakeholders (anybody with a material interest in the project's success), team members, oversight bodies, team members, suppliers and others.
Project managers need a sophisticated skill set including negotiation, analysis, problem solving, communication, planning and leadership.
The main techniques used are: defining what is to be delivered (much neglected in our industry):
* Detailed planning of time and cost
* Risk management and contingency planning
* Workload and resource planning
* Progress control
* Project close and hand over
This is the standard approach. There are well-established methodologies using this approach, such as the Body of Knowledge from the Association for Project Management, and PRINCE2, which is public sector sponsored. Various modified approaches appear from time to time, such as Critical Chain Theory, which handles contingencies and resources differently.
Les Rose is a freelance writer and clinical science consultant with Pharmavision Consulting. For more information e-mail lesrose@ntlworld.com
Related Content
Vesper Bio reports positive topline results for dementia candidate
Vesper Bio, a clinical-stage biotech developing novel oral therapies for neurodegenerative and neuropsychiatric disorders, has …
Von Willebrand disease – increasing awareness and access to vital care
Pharmafile talks to Anthea Cherednichenko, Vice President Franchise Head Haematology and Transplant at Takeda about …
Rethinking oncology trial endpoints with generalised pairwise comparisons
For decades, oncology trials have been anchored to a familiar set of endpoints. Overall survival …
