Personal View: An unfinished trip through uncertainties
Authors: Alessandro Liberati
Journal: BMJ (2004)

In mid-1997 I went for blood and other tests after an episode of back pain. A monoclonal electrophoretic peak and a spinal lesion of uncertain origin were found. After a few months of further tests I was given a diagnosis of monoclonal gammopathy of uncertain significance (MGUS). I was no longer a subjectively healthy man but a potentially ill person, with considerable anxiety. MGUS is one of those strange noso-logical entities of modern medicine—which is so good at creating “new diseases” without necessarily knowing how to cure them. The medical literature didn't help much. Several small studies reported a cumulative risk of malignant transformation of MGUSs of between 7% and 19%, with the likeliest estimate of annual risk of transformation around 1%, but without clear predictors.


Could a second transplant improve results?


I was prescribed blood tests every six months to monitor any such transformation. The years went by, during which my levels of anxiety varied, increasing at times of testing and whenever any personal or work decisions loomed. Was it worth monitoring MGUS while I was symptomless? What should be done with the slowly increasing monoclonal peak? It was not a good sign, but there was still nothing to be certain about.

An ironic sense of deja vu helped me, particularly when I was fed up with testing. I had spent several years of my professional life fighting the excesses of medicalisation in oncology, particularly unduly intensive surveillance (follow up) among potentially ill but asymptomatic people. What did we know about treating myeloma at an early stage? Not much: just three small trials, published between 1993 and 2000, failed to identify any benefit in early over deferred treatment. So, too little evidence for a fully informed decision, but enough to decide to wait—in consultation with my doctors—before opting for more aggressive treatment.

Time passed, and in 2001 another step in my “transition” was made. I no longer had MGUS but smouldering myeloma. Still, the consensus was for no active treatment. In December 2002, less than five years after MGUS appeared, I became a multiple myeloma patient. The time for thinking about treatment had come. Haematologists agree that important progress is now being made in treating multiple myeloma. The literature now documents better results for high dose chemotherapy and autologous haematopoietic stem cell transplantation than for the traditional treatments, with improvements in event free and overall survival.

I completed my first treatments with high dose chemotherapy and autologous haematopoietic stem cell transplantation in April 2003. The result: complete remission with bearable toxicity. Then came the time for the latest (so far!) decision. Could a second transplant improve results? The evidence amounted to four randomised controlled trials, whose results haven't yet been fully published (though the results of at least one had been presented at several specialists' meetings); a few observational studies; and the direct clinical experience of my doctors (who favoured the second transplant option). I eventually opted for the second transplant. I'm now busy driving up my and my fellow patients' survival curves.

What are the lessons? Firstly, that as a patient I felt even more strongly about what I've been fighting for throughout my career. Research results should be easily accessible to people who need to make decisions about their own health. The delay in the combined analysis of the four randomised controlled trials struck me as a case in point. Why was I forced to make my decision knowing that information was somewhere but not available? Was the delay because the results were less exciting than expected? Or because in the evolving field of myeloma research there are now new exciting hypotheses (or drugs) to look at? How far can we tolerate the butterfly behaviour of researchers, moving on to the next flower well before the previous one has been fully exploited? Unfortunately this is possible in a world where clinical research has become dominated by commercial interests. When you are a patient you wonder how (we) researchers can keep forgetting the principle that the priority should be collaboration for better hypotheses, not competition.

Secondly, my desire to participate in decisions was stronger than ever. As a special patient cared for by excellent doctors I was enabled to make informed choices. But I'll never forget my anguish when the central venous catheter was positioned, not knowing why it was being placed or for how long. It's also hard to forget the time I spent wondering how long it would be before my red hair came back and how often I would lose it in successive treatment stages. All these things had been mentioned, but not with the attention they should have been, even when the technical aspects of care were excellent.