Key Strategies for Planning and Executing Successful Clinical Trials

October 3, 2009

Successful Product Manager's Handbook

The most imporant thing to remember when planning a global clinical trial is very basic and almost always overlooked

A product manager's most critical task is preparing a project plan for a global clinical trial. But what constitutes a successful plan, and how do you execute it in a landscape that has become increasingly more complex? Here's a clue—It's all in the planning

Let's start with the basics: The successful execution of a clinical trial means the project is finished on time, on budget, and has a high level of quality. It only figures then that these objectives should be clearly defined before initiating any project.

This may seem obvious but, in fact, it is rarely understood: Before defining time, budget, and quality metrics, a comprehensive project plan is required, otherwise objectives will not be realistic.

The main purpose of planning is to anticipate all possible actions that will take place throughout the project. The complexity of today's trials makes such a diagnosis for each aspect of the study (in order to set realistic project objectives) imperative.

What's new

Consider first the significant changes in the way studies are conducted:

Regulatory authorities Emerging regions in particular have begun to develop or change existing clinical trial legislation and requirements to ensure patient safety.

Clinical trials logistics Importation requirements and regulations and collection and management of biological samples are different, which makes a detailed plan necessary that covers supplies, storage, and distribution.

Legal aspects Contracts with sites and local regulations and practices need to be negotiated in order to avoid delays in the study's start-up process.

Cultural differences Communication with investigators, patient-physician relationships, and patient recruitment strategies are all seriously impacted by different practices and mores.

Language barriers Principal investigators outside the US are usually fluent in English. However, this is not always the case with sub-investigators, study coordinators, or other clinical site staff.

Investigational sites Identifying the right sites to conduct clinical research is critical. In the near future, support and training will have to be given to newly established sites considering the increasingly large number of competing studies in emerging geographies.

Technology considerations Adoption of new technologies very often varies from country to country. For example, the use of e-patient diaries has had poor reception in some emerging countries due to lack of patient compliance.

Protocol design Frequently, the protocol design dose not take into account either the standard treatment in countries where the study will be performed or product reimbursement issues. Therefore, if the protocol requires patients who originally failed a treatment that is not actually available in the country, it will result in low patient recruitment rates.

Translation requirements A clear understanding of which documents need to be translated and which documents can be used in English is crucial.

Operationalize

One of the main issues when creating a project plan is to design a system where the project team does not have to start from scratch every time there is a new clinical trial.

The framework that facilitates the planning for any project team needs to come down from the very highest levels of the organization to the lowest level (and across all functions) Otherwise, each new clinical trial is like reinventing the wheel, and first studies have to be conducted all over again.

This concept changes the traditional way of planning. To a great extent, it makes the organization responsible for planning (not just the project team).

There are several tools available that can be used for the planning of a clinical trial, but they are useless if the

organization has not structured the knowledge and expertise of its people in a way that can be utilized by the entire organization.

Define the critical path

The main obstacle a project team faces is the defining of the critical path. In other words, all tasks that need to be carried out in parallel and sequentially need to be understood—when should they be completed to achieve clinical trial milestones; how should those activities be performed in order to successfully complete them; what is the end goal; and what are the organization's strategies? This needs to be structured in such a way that it can be used by other project teams that have to perform clinical trials.

If an organization doesn't have the know-how for global trials internally, the process of structuring the knowledge can be done step by step as the organization gains experience. If a company already has staff experienced with global projects, the task is to capture their knowledge and put it in the service of the organization. A project template, developed by senior staff with input from the different departments, that contains high-level details and strategies can ensure repeated successful planning—achieving study goals in the shortest amount of time.

First steps

The start-up phase of a clinical trial needs a road map that includes the following:

1 Study planning

2 Site selection

3 Site qualification

4 Local EC/IRB submissions

5 Ministry of Health submissions

6 Import process

7 Supplies importation process

8 Site regulatory package approval

9 Clinical supplies at the study site.

Once such a classification is done, define all the activities to be done in parallel and sequentially for each one of the steps (critical path), including the time needed to perform each activity.

A good understanding of the entire process and sub-process protects against forgetting any of the critical steps.

For example, you may decide to generate a sub-process for site selection activities, and then define the critical path to select sites for the clinical study. For instance:

New Venues

2 Site selection:

a. Request for site identification (2 working days).

b. Feasibility questionnaire development (5 working days).

c. Develop site identification strategy (2 working days)

d. Create the preliminary potential site identification list (1 working day)

e. Develop final potential site identification list (1 working day)

f. Contact sites. Collect the information (10 working days)

g. Identify sites for qualification (1 working day).

h. Investigator database update (1 working day)

New sub-processes can be generated until the people responsible for carrying out the activities feel comfortable and understand what, when, and who should do the work.

Next move

Once the project plan template is developed and implemented, the project manager should customize the tool according to the study-specific requirements.

Then, lock the planning by saving the baseline. This is a screenshot of the activities and timelines expected to be accomplished. The baseline should be saved immediately after the initiation of the clinical trial activities. This allows for an evaluation throughout the project of any deviations from initial expectations. It is very important that information be updated on a regular basis, with the accruals in real time and shared with the project team accountable for the deliverables as well as with senior management. A Web-based tool is the most suitable option for data entry and verification. With a clear understanding of the activities, to be done, staff can organize their activities taking into account the priorities. And managers can better project and assign resources to the project.

The purpose of any plan is to create a tool—a tool for control. Project control means evaluating the system in place and using standardized metrics to measure progress and quality. Project Managers can easily loose control of the project and its scope when they do not manage to the project plan. Deviations from the study baseline should be measured and tracked in a timely manner to identify issues, assess the impact of the changes in the plan, and apply corrective actions.

A Product Team Checklist

A risk management plan should be followed in parallel with clear mitigation strategies and contingency planning (the activation of back-up countries, or the selection of additional sites). In this way, the delays are predicted with sufficient time to resolve them efficiently. This also allows you to anticipate and address the impact of changes on the planned dates.

A final note

It is important to understand that metrics are just performance indicators. Metrics from current and past clinical trials are helpful to improve the project planning tools, redesign processes, better estimate timelines, and implement adequate strategies to conduct the studies. But they do not make a study successful.

The success of any project is in the planning phase. If all the steps to achieve the goals in the project are defined at the outset, including timelines, and they are understood by the project team, the chances of failure are much lower.

Complexity of Clinical Trials

The way clinical trials are conducted has changed significantly in the last 20 years. The turning point was the creation of the GCP guideline and the globalization of clinical research. Running a clinical trial today has become a highly complex endeavor. Here's why:

Number of Competing Studies in Breast Cancer (As of December 08)

Bigger: Clinical trials are larger than they used to be in the past. Science is making progress in almost all therapeutic areas—cardiology, infectious diseases, oncology, etc. New compounds require studies with larger number of patients to demonstrate product superiority over the existing alternatives.

More: The biopharmaceutical industry is under intense pressure to develop new medicines due to patent expiration of several marketed products. The focus on innovation is one of the drivers for the increase in the number of clinical trials that results in more studies of fewer compounds.

New guidelines: The biotech industry has produced a new way of developing medicines, which has significantly increased the number of clinical trials. Additionally, new guidelines have been introduced in terms of how clinical trials using biological products should be performed.

Global customers: The increasing attractiveness of end markets for biopharmaceutical products in emerging regions has forced the biopharmaceutical industry to look for new markets in which to place their studies.

Diego Glancszpigel is Vice President of Clinical Operations for Latin America at PAREXEL International. He can be reached at diego.glancszpigel@parexel.com

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