In response to my post "Newcastle PBC Conference #2 (4 of 4)" Barbara wrote:

"The last set, about research, sounds more realistic but less hopeful (in terms of how long it will take to unravel PBC) than what we've been hearing up to now."

This is as good a time as any for me to elaborate.

The first session of the conference Sunday night was planned to be a series of brief presentations of future trial/research proposals in Europe. The organizers cancelled it because no one had anything to share. Instead, a small group of researchers met informally to discuss their current projects. I was invited to this meeting only because I was in the right place at the right time, and the researchers did not know I was not one of them.

Several problems plaguing researchers emerged almost immediately:

• Lacking registries of PBC patients, researchers have difficulty locating sufficient numbers of us to participate in studies. Researchers need statistically significant numbers of subjects to conduct research that produces meaningful results. ("Statistically significant" means having enough subjects to study so that individual variations don't overshadow observations of the behavior of the group as a whole.)
• The typical endpoint in clinical drug trials is death. Luckily for us, the slow progression of PBC makes this outcome hard to attain over the normal period of time for clinical trials. The problem is, researchers lack other agreed upon trial endpoints.
• Liver biopsy remains the gold standard for assessing the state of a PBC patient's liver. Liver function tests tell only part of the story and the value of fibroscan is limited to later stage disease. Researchers want and need to develop meaningful non-invasive tests for determining the actual state of a patient's liver.
• Research conducted by multiple institutions on geographically dispersed cohorts must be carefully structured to insure study conditions are perfectly reproduced in all locations.

When researchers in this meeting learned I was from the PBCers and that we were funding some of our own research, those from the medical school at the University of Newcastle asked for information about our projects. I emailed Linie from the conference and forwarded her list of projects to Drs. Bassendine and Jones in Newcastle the following morning.

On Tuesday, Dr. Jenny Heathcote's presentation titled "Lessons from Trials in PBC" reviewed a number of PBC trials in the past 40 years and problems that had occured with them. The following statement from Dr. Heathcote's accompanying abstract sums it up:

"The history of clinical trials in PBC illustrates beautifully the many problems that may occur when conducting clinical research. To name but a few, these methodological issues concern study design, sample size, primary measures of outcomes, compliance and data analysis."

Later the same day, Dr. Keith Lindor's presentation titled "Wither Trials" reviewed the challenges of designing clinical drug trials for PBC. He discussed the inadequacies of measuring the subjective symptoms of fatigue and prurtitus, staging systems, diagnostic methods and prognosis. He called upon researchers to be more creative in designing trials and invited them to attend the AASLD conference in Atlanta, December 2008, titled "Design of clinical trials in primary biliary cirrhosis." Dr. Lindor discussed engaging patient participation in trials through patient support groups and specifically thanked the PBCers Organization for its support.

At the close of the conference, Dr. Raoul Poupon summarized the conference in a brief presentation titled "Priorities for the next decade." The title of his talk said it all. There are so many unknowns in PBC, so many possibilities for continued research and so few of us with this disease that we need to be realistic about the researchers' prospects of finding a cure any time soon.

The realities for us are that:

• PBC is just one disease among thousands of rare/orphan diseases, all of which are competing for scant research resources.
• We need to be willing to fund research benefitting us.
• We need to collaborate with patient support groups in other parts of the world to increase study group sizes and influence the nature of the research being performed.
• We need to insure researchers are aware of the full spectrum and extent of our symptoms. Lacking a cure for our disease, some research must instead focus on improving the quality of our lives in the interim.
• The PBCers represent only a fraction of people with PBC. Regardless of whether people choose to join our organization, we need to reach many more PBC patients than we currently do and support any effort to create national and/or international patient registries.