>> The real-world benefit of a drug can, as Prof. Dr. Thomas Wilke from the University of Wismar (Ingress-Health Wismar/IPAM eV), stated that “significantly differ from the theoretical potential” of a drug, as is typically depicted in clinical studies.
There are a variety of reasons for this, starting with the differences that can be identified between real-world and clinical studies, such as: inclusion/exclusion criteria for clinical studies, real-world treatment versus treatment in study centers and, last but not least, non-adherence and patient-side discontinuations of therapy.
Inclusion/exclusion criteria
For example, a US registry study examined how many patients in the registry met the inclusion and exclusion criteria for clinical studies for newly diagnosed multiple myeloma and could have taken part in these studies. According to a publication by Shah et al.1, 40% (563 of the 1406 registry study patients) could not have taken part in newer clinical studies in this context due to the inclusion and exclusion criteria. However, if even stricter criteria had been applied, for example a hemoglobin value of at least 8g/dl and an M-protein level of at least 1g/dl, the proportion of unsuitable patients would have even increased to 56.8%. The most common reasons why patients were excluded from clinical trials in practice was that the disease had progressed too far or that they had previously had cancer, as some oncological therapeutics can increase the risk of recurrence of a new cancer other than multiple myeloma. Furthermore, the existence of other comorbidities (e.g. elevated liver function tests) or an infectious disease was also often an exclusion criterion.
All of this leads Shah's team of authors to the core conclusion that "the strict exclusion criteria of clinical studies in multiple myeloma limit the recruitment of those patients who reflect a general patient population" and that it is also advisable to modify the standard criteria of RCTs in order to achieve an improved one RCT design to come.
Wilke also confirms this by saying that there is “generally a difference” between the potential that a drug shows in a clinical trial and the practical benefit that a drug shows in reality. On the one hand, as Shah's team of authors discovered, this could have something to do with the inclusion and exclusion criteria of clinical studies, but it could also be due to the different settings that one finds in study centers and the many, many others that are found in normal settings Everyday supplies can be found. Wilke: “Especially when it comes to therapies where it depends on how patients accept a therapy, there are big differences between compliance in centers and in reality.” This, too, has a variety of reasons, which are often very closely related Patient preferences stand.
Patient preferences
According to Wilke, it makes sense to question what patients want in almost every indication. This is the only way to find out which therapy recommendations are closer to patient preferences and which are not. The main reason for this is that not only the implementation, but also the adherence to therapy depends to a large extent on whether - according to Wilke - “the patient believes that he is getting good therapy”. Vice versa, it is also known that the therapies that patients do not like have a lower probability of being implemented and continued for a long time, since the first side effect is used as an opportunity to discontinue medication and to stop the therapy - even a life-sustaining one. Wilke: “On the other hand, a therapy that the patient is convinced of will have better adherence because it is associated with greater stamina.”
You can get to the bottom of what patients want and what they don't want by using validated preference measurement instruments, such as the Analytic Hierarchy Process (AHP) or a Discrete Choice Experiment (DCE), as used by Wilke for patient preferences RRMM therapy2 was applied.
In the first step of the study4, the various second-generation attributes of the proteasome inhibitors used in this therapy (carfilzomib, marizomib, oprozomib or ixazomib) were listed, then condensed into a size that was compatible with the study and finally sorted according to importance in focus group discussions. Seven most important attributes emerged, starting with anemia, time without disease progression, neutropenia, thrombocytopenia, mode of administration including necessary doctor visits, hypokalemia and heart failure.
Since some of these attributes could be assigned to the “blood”, they were combined into one large attribute “Side effects affecting the blood”, so that only four attributes were included in the DCE, an attribute number that Wilke used for an experiment This type is considered useful because the patients surveyed are overwhelmed with even more decision-making variations. The four selected attributes already have enough decision-making variables, since the form of administration alone is presented in three forms, which represent the addressed preparations: “1 tablet daily - plus 1 tablet weekly plus a 2-hour. Doctor visit per month”, “1 tablet daily – plus 2 tablets weekly plus one 2 hour doctor visit per month” and “1 tablet daily – plus 1 tablet weekly plus two weekly 3-4 hour doctor visits with infusion”.
But the time without progression of the disease also has three subcategories: from 17 to 20 to 26 months. On the other hand, the probability of the occurrence of serious side effects affecting the blood is only two (12 and 10%), as is the probability of the occurrence of heart failure (2 and 4%).
All of them together result in a decision set of 36 theoretical options, which was then further minimized to a decision set of 10 options so that the 84 patients surveyed could deal with them better. The survey revealed that RRMM patients primarily prefer those treatment options that allow them to use a completely oral mode of administration, and only then those that promise a longer disease-free period, followed by those that suggest a lower probability of side effects, and completely Finally, only those that minimize the likelihood of heart failure occurring. In order to maintain all of this, patients are quite willing to accept a little less effectiveness, which leads Wilke to the conclusion that the patient's preferences should play a key role in the decision-making process for the therapy of each individual patient. The study he carried out on behalf of Takeda provides important insights into this. Wilke: “Patient preferences should always be taken into account by the treating physician when a decision has to be made regarding RMMM treatment.” <<

from:
MVF editor-in-chief Peter Stegmaier