Pfizer in News

'Safety monitoring is our No. 1 priority'
August 15, 2006.

Andy Lee, the Vice-President and Worldwide Head of Clinical Study and Data Management, Pfizer Global Research and Development talks to Katya Naidu on the finer aspects of clinical trials.

What is the role of patient recruitment in the success of a trial?

Well-written protocols clearly define the population to be studied. In early phase studies (Phase I and Phase II), we typically restrict the study population, in order to gain knowledge about the drug. As we gain more knowledge about safety and efficacy, the study population is expanded to include a broader range of subjects, who are likely to be the target population for the product, when it is ultimately brought to market. We also look at inclusion and exclusion criteria to restrict use in subjects who are less likely to respond to treatment, and in subjects, where there is a higher risk for adverse effects.

What are the factors that are to be taken care of during patient monitoring?

At Pfizer, clinical trials are administered and managed by well-motivated, caring people, who make patient safety monitoring our No.1 priority. This attention to safety actually starts before we administer study drug. Firstly, we need to pay attention to the informed consent process. The investigator ensures that subjects are aware of the potential risks and side-effects of an investigational product. Pfizer focuses on ensuring that the investigators are well trained in this process. Secondly, a lot of time is invested in assessing the medical history of a subject and establishing a baseline medical assessment before entering a trial. This would typically include a physical examination, blood testing, and depending on the trial. During the conduct of a trial, we assess both subjective and objective findings on a regular basis. We rely on self-reporting from participants to report side-eff ects. We capture and report all adverse effects that occur during a trial, regardless of their real or perceived relationship to a study drug. Additionally, we will follow up on all adverse experiences, even beyond the end of a study.

How do we ensure compliance from trial patients?

We listen to patients and clinicians and value their opinions and judgment. The best way to ensure compliance is through education of trial participants and the study site staff, as this leads to trusting relationship. Again, this starts with the informed consent process. If subjects have a clear understanding of the risks and benefits associated with a study, as well as the nature and frequency of the required procedures, then they tend to be more compliant. Regular contact with the patients and listening to their needs helps compliance greatly. We also encourage sites to work closely with their Ethics Committees (or IRB's) on establishing appropriate means of supporting subjects with logistical aspects of a trial such as transport to and from the clinic. Training, building a relationship and paying attention to small details, all contribute to study compliance.

How are safety issues addressed in the trial?

Safety monitoring is extremely important to all of us involved in clinical trials and I would rate this as our No.1priority. In addition to our ethical and moral considerations, one has to remember that there is no incentive for anyone to take short cuts. An unresolved safety concern will actually harm the commercial success of a medicine, so nobody wants to advance a medicine if there are doubts. Great care is taken in assessing prior medical history and current medical status before entering a subject into a clinical trial.

What are the parameters that help decide the right dosage levels that are to be given to patients?

Dose selection is one of the most important and technically challenging parts of drug development. We use a number of techniques to select the doses to be studied in humans. In Phase I studies, we start with single, very low doses and then slowly increase the dose. If we establish safety after single doses, we progress to multiple doses and slowly increase the dose. These types of trials establish the pharmacokinetic and pharmacodynamic properties of the study drug. By Phase II, we usually have a good idea of a dose range.

As a result, multiple doses are studied in Phase II, usually over a broad dose range. Our objective in Phase II is to select the lowest, fully effective dose, but this dose also needs to have low or minimal side-effects. Selecting the optimal dose may be a trade-off between getting the best effects with the least side-effects. We also test doses in different populations with the same objectives in mind. Pharmacokinetic modelling and advanced statistical methodology are very helpful in dose selection.

What is the percentage of error you see in clinical trial primary endpoints and how can this be controlled?

The percentage is low and declines steadily as we constantly increase our scientific knowledge. We study groups of people to understand population effects, knowing individual responses vary considerably.

Having a good statistician helps in study design as they can advice on the sample size needed to demonstrate drug effects in excess of the known error. Standardisation of data collection and calibration of measurement instruments also reduces error. Adequately powered studies in the desired study population play a key role in reducing error.

What are the challenges that you have faced personally while conducting a clinical study?

I have been involved in many clinical trials and each has its own challenges. There are general categories of challenges that we overcome by doing our jobs well. Some of the challenges are designing a good study, training, recruiting to agreed timelines while sticking to the inclusion or exclusion criteria, safety monitoring—this requires 365/12/24/7 cover; ongoing and early data clean-up, interpretation and reporting of data and relationships with all stakeholders.

What are the therapeutic areas, the drugs of which are the hardest to test on humans?

A large-scale clinical trial is probably one of the most rigorous and illuminating activities in science but none are easy. Studies that require flexible dosing, complex procedures and involving critical ill subjects tend to present the most complex technical challenges. I hate to pick a specific therapeutic area, as most therapeutic areas have these complexities in certain indications.

What is the importance of pharmacovigilance in clinical trials?

This question is one that regulators, doctors, academics and industry are debating together. Pharmacovigilance has the potential to allow patients, prescribers, regulators and sponsors to have a more complete and accurate understanding of a product's risk or benefit profile in a real world setting. Through pharmacovigilance, it should be possible to capture rare events that require large sample sizes to detect, and data from a broad population, both are not always available from clinical trials conducted for registration purposes.