Otto von Bismarck is reputed to have said “Laws are like sausages; it is better not to see them being made.” You could say the same for the process of determining clinical standards for a complex disease. Although I thoroughly enjoyed the meeting I attended last weekend, Harmonising Outcome Measures for Eczema (HOME), I witnessed some sausage-making in San Diego.
Three things became clear to me during HOME. First, eczema (atopic dermatitis) is a difficult disease to diagnose and quantify improvement of. What exactly do you measure when you have an eczema patient undergoing therapy and you want to see if they’ve improved? Dry skin? Redness? Oozing? Does the area of coverage matter? The aim of the HOME organizers was to settle on universal standards.
Second, setting standards is taking a long time. This was HOME III (HOME I took place in 2010 in Germany) and people were already talking about where to hold HOME IV (possibly Japan). Over the course of the first day I became aware that in HOME III we were basically voting on questions that had been left open at the previous meeting.
Third, if you were going to choose anyone to lead a diverse, international group of dermatologists, and hope to get a democratic outcome which everyone could agree was fair, you could do no better than pick Jochen Schmitt and Hywel Williams, who led HOME III. Especially Williams—he kept things moving forward, but his genial, friendly style ensured everyone had a voice and that, though we knew we would rarely have full agreement on any topic, the criteria for coming to a decision were always made clear beforehand. (There were about 50 people in the room, all voting using those wireless clicker devices.)
So what got decided? Boy, I wish I had been taking notes. I don’t completely remember, to be honest! At some point the meeting minutes will get posted.
For the first day of the meeting, Dr. Jasvinder Singh from the University of Alabama seemed to dominate. I wondered why, especially since he apparently didn't know anything about eczema--in particular he didn't know why we were concerned about itch. Later I understood better the reason for his presence and why he was given the floor--he is an expert in "outcome measures" for rheumatoid arthritis. He was there to explain how doctors and scientists have approached characterizing a complex disease, and to help develop a system for eczema.
We spent an awfully long time deciding between two clinical “instruments” for measuring eczema severity: EASI and SCORAD. Both are essentially surveys that ask a doctor to note how severe eczema is across various regions of a patient’s skin, and then calculate a weighted sum, taking into account surface area, to produce a single final number that purports to measure overall severity.
EASI was the winner. (On a side note, I want to say how amusing it was to hear the Danish and Swedish attendees pronounce “EASI” as “ee-AH-zi,” oblivious to the acronym.)
Apparently EASI was chosen because it somehow allows a doctor to rate a patient as having severe eczema even if the condition is confined to a small area. That was my understanding, anyway. While we were discussing the matter in small groups, I argued for SCORAD in the belief that it did what EASI was later touted as doing. The general feeling, though, was that it didn't matter which one got picked, as long as we chose one, so everybody would be using the same "instrument."
Then we discussed quality-of-life measures. I was asked for my opinion, but had to admit that I hardly understood what they were talking about because the jargon was so foreign to my experience as a patient.
And next, we talked about what symptoms patients might be able to use to report their subjective experience of the disease (e.g. in long-term studies where patients have to keep diaries or report via the internet). I made a rather incoherent point that the symptoms should include not only physical measures but also psychological effects such as shame, anger, and depression. A discussion followed about whether this counted as symptoms or quality of life measures. The result was that I was asked to join the ongoing Quality of Life group. We shall see what this entails.
And finally we had a rather unsatisfying discussion of “long term control” that quickly devolved into an argument about what a flare is. I think people ran out of steam, the meeting ran out of time, and Tijuana and tequila were beckoning for several participants. Hence we didn’t reach any conclusion. Guess it'll get sorted out at HOME IV!
Being part of this felt like watching C-SPAN. At certain points, when things seemed to be going in circles, we benefited from the clear perspective of David Margolis, an epidemiologist at the University of Pennsylvania. Possibly because of his mathematical perspective, he was able to cut through the BS and say that we were using the wrong concept or debating points that had already been decided. I was told later in the meeting by a senior member that Margolis was an extremely valuable contributor. Because he had seemed so critical throughout, I was surprised when he told me afterward that he thought the meeting had made a great deal of progress.
Margolis said that the FDA is not obliged to use the standards that the HOME group decided upon when it comes to judging the success of clinical trials. So this leaves me wondering what the point was; but as the sage said, a journey of a thousand miles begins with a single step. You have to start somewhere, and where better to start than HOME?