This blog is terminated and has moved to another address!!!!

It is only recently that I started blogging.

Initially, I used Blogspot as the service for my blog.

Now I decided to change to WordPress http://mrcmeyer.com/, which I find more flexible and user friendly.

Welcome and enjoy – I hope the transition will be seamless, since I do not expect too many people to actually follow my blog at this stage 

Prevention of the "Rescue Study" Syndrome

The nightmare of any clinical research executive is the "Rescue Study" syndrome.

The definition of a "Rescue Study" is the kind of trial where recruitment is lacking far behind projections, ie. the contracted sites are not enrolling the number of patients they had promised.

Apparently, many trials end in this situation. Many teams experience that 30% or more sites end up not recruiting a single patient.

The consequences can be devastating:

1. Budget erosion and blow-out: Starting up, managing and monitoring more sites than planned significantly impacts project budgets. Other resource requirements for project management and training tend to get out of  control. In a small biotech company the available budget to the next value generating inflection point becomes severely impacted.
2. Timeline slip and blow-out: Start-up delays for new sites - and subsequent delays in recruitment can be devastating for the pre-specified timelines. Depending on the indication and the availability of patients, increasing the number of sites late may not account for the overall slip in timelines.
3. Quality compromise and give away: Identifying sites after trial initiation results in less optimal training conditions and the investment required to keep the training level high may not have been accounted for. Furthermore, sites added late in the process under suboptimal conditions may be like scraping the bottom of the barrel - including investigators less experienced or quality focused.
4. Data delay, decrease in project value and jeopardized project survival: In the worst case, overall loss in revenue and project value due to prolonged time to market - and in the worst case discontinuation of a research program

Most clinical research professionals will have found themselves in the position that although they felt they did everything right - still find themselves in the unfortunate position of needing rescue sites from time to time.

In my experience there is a good chance of a direct correlation between the timing, creativity, effort and resources you put into the feasibility and site-selection process very early in the planning and execution process - and the subsequent recruitment success. However, you have to get below the surface of the traditional feasibility approach - which is a desktop exercise without true value.

In the coming weeks I will share with you some of my experiences. I will focus on the following elements of the feasibility and site selection process:

1. Quality of and reliance on CRO data and approaches
2. Sponsor leadership, investigator relationships and communication strategies
3. Feasibility steps, timing and resources
4. Integration of pre-screening data into the site selection process
5. Site selection - and termination decisions

The dream of a clinical research professional - how to increase the likelihood of it coming true???

How to define a virtual company

While working in a fully virtual company the ongoing debate about pro's and con's of "virtual biotech companies"continues to raise thoughts.

First of all one needs to define "virtuality".

I work with four levels of virtuality:

1. Independency from geographical location

2. Project teams composed of a mix of full time employees and contractors

3. Projects orchestrated through a mix of insourced and outsourced tasks, responibilities and resources

4. IT platforms as cornerstone of team and project management and communication

In essence, technology and globalization provides today a wide range of tools and network capabilities allowing you to mix all four levels of virtuality - depending on your strategy and needs.
In reality, I believe all (biotech) companies today apply a certain level of virtuality to most of their projects.

However, in a fully virtual biotech company you can take the concept to the extreme.

In my current company the management team is geographically dispersed. The clinical project team conists of contractors only and the projects are outsourced with a mixture of tasks and responsibilities split between the internal team and the functional service providers.

With this approach we secure a high level of involvement and leadership, combining it with effective cost control, flexibility and quality control while experiencing significant project progress. And - in contrast to most peoples immediate believe - the total budget is smaller than with other models.

The fully virtual biotech model is not a longterm solution for a company.

Limitations are obviously high communication, coordination and management demands.

Nevertheless, for start up situations or short term concept evaluation projects - it definitely is a viable approach.

US biotech pursues Cetero for drug development delay costs

US biotech pursues Cetero for drug development delay costs

I came across this news today (obviously related to the outsourcing of a non-clinical project), and it made me wonder which elements in a contract with a clinical CRO that could lead to a similar action by a sponsor dealing with a clinical project.

Of course a typical contract contains many elements that can be breached by a vendor - and which could lead to a litigation process. However, would clauses linked directly to study progress make sense - and be acceptable?

Apart from the obvious fraud or non-compliance related aspects, a clinical project is definitely more complex and it will be much harder to define which specific action or decision may be responsible for a project delay (e.g missed submission deadline to an EC - due to lack of internal focus or poor management by the CRO staff?).

Obviously, sometimes  the way the CRO is managing the project may have significant impact on study progress - can those elements be identified and turned into contract clauses?

And how to calculate the loss of value associated with a delay - can loss of opportunity cost be expected to be calculated in on the indemnification and damages claims?

Would it at all be possible to initiate a litigation process on those grounds - and would it be worth negotiating terms in this direction?

Ensure negotiation power to leverage success

In a small and virtual biotech company a major concern is the risk of operational failure of your only one or two projects.

Failure could be defined as substantial delays, considerable increase in cost, jeopardized data quality and integrity etc.

The environment you have to maneuver in is marked by a high degree of pressure on timelines, cost, high need for value generation and decision makers with very little hands-on Clinical Research Management experience.

On top of this, you may quite frequently also face the need to invest significant developmental effort into your project, since you may work in an orphan disease area with only limited or no previous experience with industry sponsored drug development projects amongst investigators/CRO's, no well-established primary endpoints, no well-established conventions for relevant trial designs etc. This further increases the level of uncertainty of your project assumptions - and can only be addressed to a limited degree throughout the planning and start-up phase.

As the leader of this process you must keep focusing on how to secure power to impact, change and adapt  at any time point and any aspect of the process and the ability to react to as many unexpected events as possible.

The key question is: "How to secure sufficient leverage and negotiation power in the collaboration with your vendors?"

First of all, disregard the viewpoint "Our company is a small player and therefore we will never be able to obtain the necessary impact, attention, negotiation power"..... Then you are setting yourself up for failure.

By focusing on the following elements you can keep enormous amount of power - even as a small player:

• Acknowledge the fact that clinical projects are complex, filled with uncertainty, based on assumptions - and are fully dependent on people with different competencies, experiences and personal agendas. Make this the key focus point when you define your project and outsourcing strategy.
• Build expertise in-house - and use your knowledge to define and lead the work that needs to be carried out
• Be very detailed in your contract specifications. The more detailed - the more negotiation power
• Consider a team-integration approach - only outsource true operational aspects - and keep all coordination, strategic and leadership aspects in-house
• Do not be tempted by the notion that project management is purely operational and has no strategic elements
• Create a vendor selection strategy before you initiate your vendor selection process
• Perform diligent vendor identification and selection exercises
• Embrace the fact that vendors have other agendas then you - and ensure to create win-win solutions in your negotiations
• Create competitive vendor selection and contract negotiation processes, hereby keeping negotiation power to the very end ("competitive vendor negotiation" means negotiating with several vendors in parallel)
• Do not sign a "Letter of Intent" - negotiate your contracts to the end before kicking-off your project
• Create milestones based on underlying vendor processes 
• Ensure a way out in your contracts
• Be genuinely prepared to terminate contracts - and build your team and strategy in a way that gives you the power to do so

As you can tell from the above - the cornerstone of a successful clinical project is defined during the planning and start-up phase - prioritize it - do not rush it!

Virtual biotech - a sustainable business model?

This morning the newly appointed Chairman of the Danish Biotech Association Martin Bonde expresses his concern regarding the sustainability of the virtual biotech model (http://medwatch.dk/).

The challenge he sees appears to be a lack of committment and progress associated with the virtual model - due to the perceived lack of internal resources - and lack of focus by the contracted vendors.

What Martin points at is a real issue and a real challenge - and requires skills and experience to handle.

However, the solution is not to shed doubt on the business model.

The job can certainly be done in a virtual set-up with great speed, enthusiasm and commitment - both by the internal team and the contracted vendors. The trick is to tailor the set-up right for the specific project. And to understand that vendor management is the ultimate skill required in this setting.

It is a classical mistake to believe that a "virtual set-up" equals having only a single project manager making contracts with vendors. This model fits sometimes (only rarely) - and usually the biggest compromise - from the investors point of view - is lack of progress, lack of financial control and sometimes even lack of success. And it always seems to come by surprise. Since time is one of the most important cost-drivers in this field it is indeed surprising that so many people continue to believe that the "virtual set-up" equals a single project manager.

You do not need to employ more people in full time positions to be more successful in a virtual set-up. Virtual teams work very well and give you all the competences, commitment and support you need to manage your vendors efficiently and smart - and the beauty is that they provide it on an as needed basis.

By setting your team in this way you acknowledge and embrace two key elements of outsourcing clinical projects in a virtual environment:

1. You capture your vendors agenda. It is their business to serve multiple costumers. And it is NOT their agenda to do it fast! You need to embrace that fact - and build it into the way you set-up your project team - and the way you define your outsourcing strategy. In some rare instances you may be successful with one project manager. In most cases, however, you will need a team. Considering a virtual team to manage your project in a virtual set-up - this may be the key to your success.
2. The significance of entrepreneurial leadership. Leadership is the key especially in virtual set-ups. Leadership can not be expressed by signing contracts and letting go on your leadership tools through contracting of complex projects to a single vendor who also has other agendas. Depending on the nature and complexity of the project - do not forget to set the right framework for being able to display leadership.

Sustainable business models have been lacking in the biotech field. But the current paradigm shift that appears to be happening can in fact be supported by success stories. 

But like everything else in life - it is a challenge to get i right - and usually requires some failures on the way.

Martin Bonde

Christian Meyer

Oversight strategy - the key to your overall execution success

Quite often the debate goes on in the management team of a biotech company about the minimum level of "Quality" required to ensure the success of a specific clinical project in the biotech environment where resources are limited.

It is an important discussion, since the overall budget requirements always are important in this environment - and the right balance between internal and external resource requirements has to be obtained.

But it is also often a difficult discussion between parties with quite different pre-requisites - and understanding - of the definition and notion of "Quality".

The majority of decision makers (investors, management team (CEO, CSO, COO, CFO)) in a typical small early stage biotech company are not particularly experienced with regard to understanding clinical trial management concepts or principles when entering the clinical stage. Many times there is the belief - also among unexperienced clinical research management professionals -  that handling of a specific clinical project can be purchased as an "off the shelf" product at a CRO.

If the discussion goes in the direction of: "We do not need the highest level of quality", or "We do not need to spend resources on quality at this stage of development", you are on the wrong track - and tend to discuss the wrong aspects of the conception of "Quality".

The successful biotech teams have understood how to use "focus on quality" as one of the key clinical project management and outsourcing tools in an environment with limited resources. "Quality" in this respect means a toolbox that allows you to specify, track and manage your activities at a high level of detail - which in return increases your ability to hold your vendors accountable for what you have contracted them to do. Study progress, budget and timeline control are collateral benefits of this approach.

By putting a sign of equation between "quality management" and "clinical project oversight" and building quality management tools into your project management set-up - you find that you suddenly have all the tools you need to ensure success - exactly what you need when you only have limited resources.

If structured in the right way, these tools become the most important means to manage your vendor agreements.

The following elements need to be taken into account when designing your clinical project oversight:

• Type of disease: Rare disease vs common disease (incl. competition for patients)
• Stage of the drug - incl available knowledge about the safety profile
• Complexity of the protocol (amount of data, no of visits, nature of primary endpoint, types of assessment)
• Size of the trial (number of patients, number of sites, geographic spread)
• Experience of investigators with drug development trials
• Experience of monitors/CRA's with the therapeutic indication

The following tools and elements should be considered when attempting to leverage the design of your clinical project oversight strategy in a small biotech company and transfer it into your outsourcing strategy:

• Vendor identification and selection strategy
• Local vs remote
• Geographic spread
• Experience level
• Number and type of services
• Availability of electronic systems
• Choice of electronic systems
• eCRF system
• CTMS system
• TMF (fully or partly)
• SAE reporting systems
• Design of 
• Outsourcing strategy (type of services; functional outsourcing vs full outsourcing)
• Training plan (vendor staff training, site staff training)
• Centralized monitoring plan
• Audit plan (site level, vendor level)
• Co-monitoring plan
• Project management structure
• In-house team (full time employees vs consultants)

By getting the balance right you will fulfill the need to secure those elements that are important to facilitate regulatory decision making:

• Reliability of critical efficacy (primary and secondary endpoints) and safety data
• Handling of subject safety and ethics during the trial
• GCP compliance
• Data integrity

And at the same time obtain control of timelines and resources through optimal vendor management and investigator relations.