Table 5.

Application of the Wilson and Jungner criteria and the additional recently proposed emerging criteria to multiple myeloma.

Criteria	Applies to MM?	Comment
Original criteria49
The condition sought should be an important health problem	Yes	MM is the second most common hematological malignancy with 31,810 new cases and 12,770 attributed deaths in 2018 in the United States alone53
There should be an accepted treatment with recognized disease	Yes	Treatment for MM is widely available and international organizations recommending specific care for MM54
Facilities for diagnosis and treatment should be available	Yes	This at least applies to developed countries
There should be a recognizable or early symptomatic stage	Yes	MGUS and SMM are clearly established entities1 and precede all cases of MM5,6
There should be a suitable test or examination	Yes	SPEP, IFE, and FLC assays are sensitive and specific tests for MM and its precursors and can easily be repeated to confirm the diagnosis55
The test should be acceptable to the population	Yes	Screening is done by a blood test which is widely acceptable
The natural history of the condition, including development from latent to declared disease, should be adequately understood	Yes	Although there is still much to learn about the underlying pathogenesis of MM, a wealth of literature on the subject exists56. Furthermore, the natural history of MM and its development from precursor disorders is adequately understood with studies including decades of follow-up available57
There should be an agreed policy on whom to treat as patients	Yes	Although this is currently a moving target, there are clear guidelines on whom to treat, i.e., those with end-organ damage or myeloma defining events. In light of recent evidence, however, treatment might become available at even earlier stages20,21,58. If and when such early treatment is appropriate, there are institutions in place that will include such treatment in their guidelines
The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditures on medical care as a whole	Unknown	There are currently no screening studies available for MM and its precursor conditions and a cost-benefit analysis is not available. This will be addressed as part of the iStopMM study
Case finding should be a continuing process and not a “once and for all” project	Yes	Since blood sampling for screening can be carried out at any time MM screening can be a continuing process
Emerging screening criteria50
The screening program should respond to a recognized need	Yes	Although survival in MM has dramatically improved in recent years17–19 the disease remains a major burden on affected individuals and healthcare systems59
The objectives of screening should be defined at the outset	Yes	The objectives of screening for MM are clear: providing earlier treatment for MM
There should be a defined target population	Unknown	Currently, a well-defined target population for screening does not exist. This is addressed with regards to age, sex, and various other measures in the iStopMM study. However, due to the dominant white ethnicity of the Icelandic population, race cannot be addressed in the iStopMM study. Another study, the PROMISE study, focuses on the impact of screening in individuals of African descent. (ClinicalTrials.gov Identifier: NCT03689595)
There should be scientific evidence of screening program effectiveness	Unknown	The objective of the iStopMM study is to provide this evidence
The program should integrate education, testing, clinical services, and program management	Yes	There are excellent patent resources available in MM and its precursor disorders. Any screening program would be able to fulfill this criterion
There should be quality assurance, with mechanisms to minimize potential risks of screening	Yes	This organizational issue can be solved in MM screening since there are clear response criteria60 and accepted relevant endpoints like survival available for MM
The program should ensure informed choice, confidentiality, and respect for autonomy	Yes	This is a practical issue that does not require scientific proof of concept, although such proof is provided in the iStopMM trial
The program should promote equity and access to screening for the entire population	Yes	Since the cost of MM screening is relatively low and requires no specialized equipment at the point of patient care, equity in testing is therefore feasible. Follow-up for precursor disorders and treatment for MM can however be expensive and could lead to inequity in non-universal healthcare systems
Program evaluation should be planned from the outset	Yes	The practical issue of evaluation is possible for MM as proven by the methodology described above
The overall benefits of screening should outweigh the harm	Unknown	This is the principal study objective of the iStopMM study