The role of observational studies in optimizing the clinical management of chronic myeloid leukemia

Abstract

Survival has increased dramatically for patients with chronic phase chronic myeloid leukemia (CP-CML) using BCR-ABL targeted tyrosine kinase inhibitors, such that life expectancy is expected to approximate that of patients without CP-CML. Randomized controlled trials (RCTs) and observational studies provide valuable insights into the management of chronic diseases such as CP-CML. RCTs are undoubtedly the backbone of clinical research, and the 'gold standard' for evaluating the efficacy and safety of new therapies. However, many questions surrounding the optimal management of patients with CML remain unanswered, and it is widely accepted that these questions will be best answered by evaluating the use of available therapies in clinical practice. Observational studies can extend the knowledge base beyond the clinical trial setting and thus capture a more accurate picture of everyday clinical practice, particularly patients' experiences of long-term CML treatment. There is therefore growing interest in and appreciation of the value of observational research. This review article will examine the relative merits of RCTs and observational studies in the setting of CML, highlighting those factors - such as the advancing age of the CML patient population and growing importance of patient-reported outcomes - that mean that observational studies should play an important role in shaping clinical practice. This article also provides an overview of what observational studies have told us thus far about the optimal management of patients with CML, outlines some of the key remaining unanswered clinical questions in CML, and summarizes ongoing observational studies designed to provide answers to these key questions.

Tyrosine kinase inhibitor interruptions, discontinuations and switching in patients with chronic‐phase chronic myeloid leukemia in routine clinical practice: SIMPLICITY

“…Based on the results of randomized controlled trials (RCTs) dasatinib (Sprycel, Bristol-Myers Squibb), nilotinib (Tasigna, Novartis), and bosutinib (Bosulif, Pfizer) have also been approved as first-line therapy. 20 The circumstances under which initial TKI is selected, why it is discontinued and how a second-line TKI is chosen have been studied in the USA and Europe. [14][15][16] Complementary to the wealth of clinical trial data supporting the efficacy and safety of imatinib, dasatinib, and nilotinib, [15][16][17][18][19] observational studies contribute further insights to inform clinical decision making.…”

Pharmacoepidemiology: Using randomised control trials and observational studies in clinical decision‐making

“…Indeed, some have been running for many decades, such as the Framingham Cardiovascular Cohort Study, operating for over 65 years . This advantage of time means that observational studies are able to provide important data on patients' long‐term experiences, particularly in the setting of chronic diseases with a natural history over many years …”

Dasatinib in Firstand Second-Line Therapy of Chronic Myeloid Leukemia: Efficacy, Safety and Quality of Life

“…Современные возможности лечения хронического мие-лолейкоза (ХМЛ), связанные с появлением ингибиторов тирозинкиназы (ИТК), позволяют достичь длительного контроля над заболеванием [1][2][3]. Применение има-тиниба, который является первым ингибитором BCR-ABL-тирозинкиназы, у пациентов с ХМЛ в хронической фазе привело к значительному улучшению показателей общей и выживаемости без прогрессирования [4,5].…”

“…Следует отметить, что результаты клинических исследований не всегда воспроизводимы в реальной практике из-за жестких критериев включения. Это и возрастные ограничения, и отсутствие выраженных сопутствующих заболеваний, а также строгие требо-вания протоколов исследований, предусматривающие увеличенную кратность визитов и повышенную привер-женность пациентов к лечению [3,30,31]. Ограничения рандомизированных клинических исследований широко представлены в литературе [32,33].…”