Measurement Error in Real-World Comparative Effectiveness Studies of Progression Free Survival in Multiple Myeloma

Randomised-controlled trials (RCTs) are research studies used to determine how effective a new treatment is in comparison to a different, more established treatment. In an RCT, patients are randomly assigned (like flipping a coin) to either receive the new treatment or a control treatment, which could be a proven treatment or placebo, i.e. something that looks like medicine but has no actual effect. This helps researchers compare the benefits and side-effects between the two. Sometimes it’s not possible to do this kind of study; for example, if a new treatment seems to be highly effective and safe in early studies, it might be unethical to not provide it to those eligible to receive it. In these cases, researchers will instead use external data sources such as electronic health records to create an external control group. This approach allows the new treatment to be compared to a control treatment in what is referred to as an indirect comparison. However, differences in how frequently patients are monitored and measured and the type of measurement tests used, can make indirect comparisons difficult. If differences in how treatment effect is measurement are not considered, measurement error bias may arise, and study conclusions may be inaccurate.

A popular method for measuring the effect of treatment is to assess the presence of disease progression. If disease progression occurs, then this indicates that the treatment is no longer effective. However, measuring disease progression can be susceptible to the forms of measurement error bias described above.

Disease progression is frequently used to measure treatment effect in trials of patients diagnosed with multiple myeloma (MM). MM is a type of blood cancer which affects the way white blood cells make antibodies. MM is the second most common blood cancer, and accounts for 1% of all cancers and about 10% of all blood cancers. Compared to people without MM, patients with multiple myeloma are only 55% as likely to survive for at least 5 years. There is no known cure, however new treatments developed in recent years have allowed patients to live longer. Unfortunately, most patients’ disease will eventually stop responding to treatment and available treatments for these patients are limited. 

It is increasingly recognised that indirect comparisons have the potential to support the development of new treatments for MM. However, given concerns about bias, the impact of measurement error on these types of study must be investigated. The aim of this study is to quantify the impact of measurement error bias in indirect comparisons of disease progression in MM patients.