TOP TEN RISKS FOR CLINICAL TRIALS

The top ten risks will vary in each trial based on many factors, so that a composite list for all trials cannot be accurate. This list also reflects the author’s views and experience, which will not mesh completely with those of each of his readers.

These risks are presented in reverse order of importance.

10. Too many patient visits are scheduled and/or too much time and effort of
patients are required at some or all visits
9. Outsourcing to CROs and vendors is not done correctly or efficiently (e.g., CROs
are not carefully monitored, communication plans among all groups in a trial are
incomplete or inefficient)
8. The patient retention strategy is inadequate, so that too many patients leave
the study and follow-up for important data from those who drop out or are
discontinued is not adequately planned in advance
7. The trial is stopped too early after an interim analysis and the data are
inadequate to convince regulators and/or practicing physicians about the
product’s safety or efficacy
6. Too many procedures and/or tests are conducted at some or all patient visits.
This often results from simply adding new procedures and/or tests to the last
protocol performed with the agent
5. The primary trial objectives either represent a baby step forward from the
previous trial or too great a giant step from the previous trial (i.e., the
primary objectives may not be the best ones to choose)
4. The investigators chosen to conduct the trial are not the most appropriate ones
for any of dozens of important reasons, including lack of adequate due diligence
3. The trial design chosen to address the objectives is not the most appropriate
nor efficient one
2. The inclusion/exclusion criteria are too restrictive and have limited the
potential population more than is necessary
1. The recruitment strategy is not adequate to obtain the necessary enrollment at
the necessary speed

To learn more about these and other risks refer to “Guide to Drug Development: A Comprehensive Review and Assessment” by Bert Spilker. Published by Lippincott, Williams and Wilkins (Philadelphia), 2009.

Find creative colleagues, both inside and outside your company or organization whom you can approach for informal or formal consults. Determine if any of these can or should be approached to possibly become your mentor, or simply a trusted peer.

Eliminate hidden agendas and company politics whenever possible, if they interfere with progress and efficient development. A direct way to approach this (when appropriate) is to speak with (or remove) major perpetrators. An indirect way is to discuss this issue with their supervisors, those who lead meetings or projects where this occurs.

Try to present a range of possible options for discussing an issue or problem with others instead of strong recommendations.

Some workers want to only present a highly polished work product, rather than a rough plan, outline or partially completed work so that others can provide input. It usually is preferable to complete work products in an iterative manner so that you have buy-in from the necessary people.

While large and many medium size pharmaceutical corporations go through periods of divesting businesses and acquiring new businesses, they should always try to avoid being dependent on only one or a few products.

All companies (including virtual companies) need both leaders and managers. Each employee or advisor should know their roles, and leaders should not act as managers and vice versa.

International pharmaceutical companies may be managed using a structure/model that varies from a totally centralized one to one that is totally decentralized, where each part (e.g., based on the country, function or other factor) acts independently and seeks to coordinate with others when possible. A dual headquarters model is sometimes used (e.g., Europe and US).

Seek ways to create an environment and milieu that facilitates discovery, where imaginative scientists can communicate, create and flourish.

Managing discovery oriented scientists cannot be heavy handed using the same control mechanisms and systems that a company uses to move development projects and marketed products forward. Activities in development and marketing can be more tightly planned, controlled and reviewed than those involved in discovery.

Drug development comes with only one guarantee. The guarantee is that there will always be surprises.

When you cannot solve a complex problem easily or completely, divide it into pieces and address each of those separately. Almost all problems or issues can be divided into multiple components, each of which may be more easily resolved than a single large one.

A company must identify and align its vision, mission, objectives, goals, strategies and tactics. Just as a car needs periodic alignments and checkups, so will a company have to re-align these characteristics from time to time.

Every major function within a company should identify its own mission, objectives, goals, strategies and tactics, and ensure that they are aligned with those of the corporation. Smaller groups within each major function must do the same.

A company must know what it wants to be when it matures. Nothing is more frustrating to the staff than a company that flounders from one vision to another without the full support of its members. Major changes must be accompanied by a sound rationale and open discussions with and among the staff.