AFTER 50 POSTINGS I WOULD LIKE TO KNOW IF ANYONE IS READING THIS BLOG AND FINDS THE SHORT LESSONS AND COMMENTS OF INTEREST AND VALUE. IF SO I WILL CONTINUE THESE FOR AT LEAST ANOTHER YEAR. IF I DO NOT RECEIVE AT LEAST A NUMBER OF RESPONSES I WILL CONCLUDE THEY ARE NOT BEING READ AND MAY NOT CONTINUE. PLEASE RESPOND TO BSPILKER@COMCAST.NET TO LET ME KNOW THAT THEY ARE BEING READ AND THAT READERS WOULD LIKE THIS BLOG TO CONTINUE. THANK YOU.

The number of patients available to join a trial drops by about 90% the day a trial begins. This is often referred to as "Lasagna's Law" and is mitigated by using only inclusion criteria that are definitely required, by reviewing potential enrollees prior to choosing the site investigators and by having a well-developed recruitment strategy.

Phase 4 trials can be monitored less intensively than investigational period trials.

Every biotech and pharmaceutical organization with products in clinical development must have a designated recruitment specialist, either in-house or at the CRO, whose role is to help ensure sufficient enrollment in the trial. Not to do so risks major delays and possibly major issues and problems.

Monitors must understand the intensity and lattitude that is required and they are allowed in their monitoring activities. Sometimes it is only necessary to monitor high enrolling sites or a random group of sites in large trials. In mega-trials it is impossible, and not regulatorily required, to monitor these trials as extensively as pivotal or many other types of trials.

A "fat" development plan refers to one that has an excessive number of clinical trials, whereas a "lean" one is the opposite. These terms can also be applied to the amount of data collected in an individual clinical trial and also the amount of data collected on an individual patient.

Keep all SOPs up-to-date and ensure that they cover relevant topics for the company. Consider having staff read them every two years and to sign a document attesting to that fact.

To minimize the time and cost of screen failures do the screening in separate stages. First, ask the most important questions to "qualify" patients to be screened, such as during a telephone call. Second, conduct the initial easy to conduct tests and procedures necessary to ensure they are able to pass most inclusion criteria. If one needs to have a third stage then separate the expensive tests/procedures from the less expensive ones and only conduct the expensive ones in patients who have successfully passed the less expensive ones.

It is often useful to ask: "What does that mean?" particularly if you are unsure of the meaning. The person may mention something that you definitely do or do not agree with, but hopefully better understand.

Define a patient as being "in" a clinical trial as late in the process as possible. This is done both by randomizing as late as possible and by saying that at least one dose must be given, and possibly add that one set of measures must be made after the first treatment. Then the ITT analysis is more fair than if you randomize long before treatment is started.

Creating a recruitment strategy is like the step therapy model in treating hypertension. One starts with one or two elements and adds others as needed to achieve the desired enrollment goals. In the recruitment strategy one can initially plan to add additional elements at pre-determined times, and to stop or use periodic pulsed elements (e.g., radio advertisements once every week).

Good ethics and high scientific and medical standards can and should be used as a means to beat the competition. Regulatory agencies may raise the bar for others to meet in developing similar products if you have raised the bar yourself.

Every clinical trial should conceptually begin with the primary objective(s). If there is more than one, they should be few in number, clear, succinct and also detailed. This allows one to choose the most appropriate trial design to obtain the data necessary to study and evaluate them objectively. Indicate the specific endpoint, specific patient population, specific dose, specific length of time, the specific test and control groups, etc. These details in the primary objective will better enable you to design the optimal trial to evaluate that objective.

An objective stated as: "to study safety" or "to study efficacy" is not adequate and is incorrect as a meaningful objective. At the minimum, "safety" must be defined by each of the tests to be used.

While there is rarely any limit imposed on the number of secondary objectives in a protocol one should always consider if there are more than ten or so, if some of them can be relegated to subgroup analyses or tertiary objectives.

An objective is never expressed as: "To show that X" but as: "To evaluate whether X," because the former literally implies that the trial is set up to show a preconceived conclusion rather than to see how the data will turn out as one evaluates a scientific/medical question.

Any topic can be described in 1,10,100,1000 or in ten thousand units of time and words. Ensure that you are not using more than the appropriate amount for the situation, or too few to convey your message.

Company decisions should be made for the long term benefit of the company and not for the benefit of the next quarterly statement.

Interpreting risks and benefits of a drug often depends on who is at each end of the syringe.

Many questions and decisions can be addressed by asking the question: Is the juice worth the squeeze?

Before scheduling a trip, ask if it can be replaced by a teleconference or a web-based meeting.

Many business meetings can be held at airport hotels with less wear and tear on participants. Have you ever tried to go by taxi from Chicago's O'Hare airport to downtown in rush hour?

The greater the Medical Need for a new product and the greater the Medical Value of a new product in meeting this medical need, the faster the regulatory agencies, physicians and patients will want and lobby to have the product introduced onto the market.

The more hierarchical an organization, the more likely it is to have stronger silos acting as barriers to efficient and open communications.

Never start to answer a research question that requires an experiment, study or research until you are certain that it is the right question to address.

Compassionate plea protocols may serve in some cases as a second trial for an orphan drug to obtain approval. Even if it does not it often allows one to collect valuable data, if designed correctly, and if the optimal type(s) of patients are enrolled.