Scores versus clinical profiles in therapeutic decisions: a positive example from the Italian Medicines Agency (AIFA) decisions in the field of osteoporosis

Clinical Rheumatology, Jan 2018

Antonio Del Puente, Antonella Esposito, Luisa Costa, Francesco Caso, Raffaele Scarpa

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://link.springer.com/content/pdf/10.1007%2Fs10067-018-3995-4.pdf

Scores versus clinical profiles in therapeutic decisions: a positive example from the Italian Medicines Agency (AIFA) decisions in the field of osteoporosis

Clinical Rheumatology Scores versus clinical profiles in therapeutic decisions: a positive example from the Italian Medicines Agency (AIFA) decisions in the field of osteoporosis Antonio Del Puente 0 1 Antonella Esposito 0 1 Luisa Costa 0 1 Francesco Caso 0 1 Raffaele Scarpa 0 1 0 Rheumatology Unit, Department of Clinical Medicine and Surgery, School of Medicine and Surgery, University of Naples Federico II , Via Sergio Pansini 5, 80131 Naples , Italy 1 Antonio Del Puente Introduction The attempt to mathematicise the cognitive approach to reality can be traced back to ancient Greek culture. Mathematics is a most powerful cognitive tool, whose potential is evoked by the name itself, as mathesis means Blearning reality^. Actually, and surprisingly enough, reality reveals a peculiar correspondence between this approach and its intrinsic constitutive mechanisms, and the development of a favorable cultural context has disclosed the operative potential of this approach. The link between science and praxis has changed completely our relationship with reality. Mathematization has been a driving element also in the field of medical care, generating levels of progress that have recently involved also the strict clinical milieu. An example of this is the contribution to the definition of risk profile for a given patient to develop a given outcome. In Rheumatology, for instance, the use of diagnostic scores is employed to assess the activity profile of the disease in patients with Rheumatoid Arthritis (RA) using the 28-joint Disease Activity Score (DAS28) [ 1 ], or to calculate the risk of fragility fractures, using the fracture risk assessment tool (FRAX) [ 2 ]. The importance of these tools, however, has generated a tendency deserving careful analysis, as it goes beyond a specific medical field, and that, in our opinion, requires a more general evaluation for the possible problems that may ensue. Indeed, this issue evolves in a totally different way and with very specific implications when the approach is * automatically extrapolated to the domain of therapeutic decision-making. Scores in therapeutic decisions Using mathematical scores to define a therapeutic approach raises issues that cannot be underrated. Here are the three main issues. 1. Overestimating the conditions for the indications to treatment. As said, in RA, DAS28 is obtained combining four numeric variables: tender joint count (TJC), swollen joint count (SJC), visual analogue scale (VAS), erythrocyte sedimentation rate (ESR) [ 1 ]. DAS28 is used to evaluate the activity of arthritis in clinical trials, but this score is being increasingly proposed as guide to treatment decisions [ 3 ]. However, several other rheumatologic conditions may cause overestimation of DAS28 thus confounding its relationship with the clinical profile of arthritis. VAS and TJC, for example, can also be affected by other causes of pain not generated by arthritis, as for example fibromyalgia. In addition, osteoarthritis, for example, can generate pain in the hand and knee joints—conditions also included in the DAS28. The score can be high, and therefore suggestive of active arthritis, for other causes, making it less reliable when dealing with questions as relevant as a therapeutic decision [ 4 ]. 2. Scores may emphasize statistically significant conditions that are not relevant from a clinical point of view. A recent article analyzed the results of trials comparing the radiological progression of arthritic damage (assessed using the Sharp/van der Heijde score), in patients treated with biotechnological drugs or with methotrexate (MTX) [ 5 ]. For instance, the TEMPO study on patients with early RA showed a radiological progression of 3.3 units in two years of treatment in patients randomized to MTX, compared to 1.1 units in patients on etanercept, and −0.56 units in patients treated with a combination of MTX and etanercept [ 6 ]. The difference was statistically significant, although, a 3.3 units difference is 0.7% of the total number of units in the Sharp/van der Heijde score, where the total score is 448 units. One objection could be that rarely patients develop damage as high as 50% over the highest value, suggesting that a value of 224 be considered as the real value, i.e., 50% of the highest value. Here again, a 3.3 units variation in a two-year period is 1.5% of this value. This change would not be clinically detectable in the single patient, whereas a clinically relevant change (5 to 15 units) would be observable only after several years and would not be of any practical use for patient management [ 7 ]. Similar results in patients with early RA have been reported with other biotechnological agents, with statistically significant but not clinically relevant differences vs. MTX in the individual patient [ 8 ]. Underrated role of the physician. Tendentially, the risk with the use of scores in therapeutic decision-making is that the professional role (...truncated)


This is a preview of a remote PDF: https://link.springer.com/content/pdf/10.1007%2Fs10067-018-3995-4.pdf

Antonio Del Puente, Antonella Esposito, Luisa Costa, Francesco Caso, Raffaele Scarpa. Scores versus clinical profiles in therapeutic decisions: a positive example from the Italian Medicines Agency (AIFA) decisions in the field of osteoporosis, Clinical Rheumatology, 2018, pp. 575-578, Volume 37, Issue 3, DOI: 10.1007/s10067-018-3995-4