We would like to ask you to take part in one of the largest scientific studies ever conducted in Iceland.
The aim of the study is to examine the possible benefits of screening for monoclonal gammopathy of undetermined significance (MGUS), the precursor to myeloma.
The only thing required of you to participate is to grant your informed consent. This can be done by:
Widespread participation is key to the success of the study.
Your participation matters.
We hope you will join us.
The study is conducted by the University of Iceland, the Icelandic Cancer Society, and Landspítali University Hospital and is titled iStopMM (Iceland Screens, Treats, and Prevents Multiple Myeloma). The aim of the study is to examine what effects screening has on the outcome of patients with monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic precursor to myeloma.
Your participation is entirely your choice. Before you make up your mind, it is important that you are informed of what the study entails and how it will be conducted. Please take some time to read this information and discuss it with your family or friends. If you find the information insufficient or feel you have unanswered questions, feel free to contact the study team by sending an e-mail to email@example.com or by calling +354 896-0022.
Myeloma is a cancer of the bone marrow. Symptoms of the disease are often not evident until after seriously affecting the patient’s health. Approximately 25 individuals are diagnosed every year with myeloma in Iceland and around 120,000 individuals worldwide. Recent years have seen major strides in myeloma research and in medical treatment of myeloma, greatly improving the prognosis of those who are diagnosed with the disease.
Monoclonal gammopathy of undetermined significance (MGUS) is the precursor to myeloma, and individuals who have this precursor have certain proteins in their blood called monoclonal antibodies. MGUS, however, is not a cancer, and most of those who have MGUS never develop myeloma. Approximately 1% of individuals with MGUS develop myeloma each year, with approximately 4–5% of the Icelandic population over the age of 50 having MGUS at any given time.
The study will be led by doctors at the University of Iceland and at the hematology unit at Landspítali University Hospital in cooperation with the Icelandic Cancer Society, the biotechnology firm Binding Site in the UK, and the Memorial Sloan Kettering Hospital in the U.S. The study is performed to assess the impact of screening for MGUS with regard to patient prognosis and at the same time, to determine the best possible diagnostic processes and follow-ups of such individuals, as well as the generic effects of such screening on quality of life.
Participation in the study only requires your informed consent, which you can grant electronically on this website or in writing by signing the consent form that you should have received by mail in a purple envelope and mailing it back in the envelope provided. No further action is required of you at this time. If you have a blood test (for any reason) during the next three years, we will receive the remains of the sample, which would otherwise be disposed of. You do not need to have any blood tests done solely for the purpose of this study or take any further action at this point. If you have not undergone any blood testing after three years, we may get in touch with you and ask you to come in for testing. Your blood sample will be sent to Binding Site in the UK, where it will be screened for MGUS. No personally identifying information will be included with the sample.
We hope this study will add to our knowledge of the natural progress of MGUS and the prognosis of those who have this condition. Widespread participation is key to the success of studies like this one.
All residents of Iceland born in 1975 or earlier will be invited to participate in the study.
The majority of participants will not be diagnosed with MGUS and will not be called in for evaluation or further study. However, a small part of that group, selected randomly, may be invited to give a blood sample for further analysis as a control group to those diagnosed with the precursor.
Approximately 4–5% of participants will be diagnosed with MGUS and will be randomly assigned to one of three study groups:
Group 1 will not be called in for interviewing or any follow-up blood sampling. At the end of the study, all participants in Group 1 will be contacted and informed of the results of the screening, with recommendations for appropriate monitoring, based on the results of this study.
Group 2 will be called in for an interview and for informative purposes. A review will be made of participants’ earlier state of health, a physical examination will be carried out, and blood and urine samples will be taken. A blood sample, approximately 20 ml, will be taken at the first interview, after 6 months, and each year subsequently, for a part of the group, or more frequently as the need arises. The purpose of this sampling is to monitor the progress of the disease and for research purposes. Blood samples will be collected in order to assess, for example, hematological parameters, kidney function, cardiac function, inflammation, the presence of certain proteins, and changes in DNA. A urine sample will be collected at the beginning of the study, after 6 months, and annually thereafter, in order to monitor the progress of the disease and for research purposes.
A part of this group will be offered imaging studies and bone marrow biopsy at their first visit, in order to confirm the diagnosis, and again at the end of the study. Additionally, bone marrow samples will be collected as deemed medically necessary.
Group 3 will be called in for an interview and for informative purposes. A review will be made of participants’ earlier state of health, a physical examination will be carried out, and blood and urine samples will be taken. A blood sample, approximately 20 ml, will be taken at the first interview, after 6 months, and each year subsequently, or more frequently as the need arises. The purpose of this sampling is to monitor the progress of the disease and for research purposes. Blood samples will be collected in order to assess, for example, hematological parameters, kidney function, cardiac function, inflammation, the presence of certain proteins, and changes in DNA. A urine sample will be collected at the beginning of the study, after 6 months, and annually thereafter, in order to monitor the progress of the disease and for research purposes.
All those included in this group will be offered imaging studies and bone marrow biopsy at the first visit, in order to confirm the diagnosis and possible bone alterations. Additionally, bone marrow samples will be collected as deemed necessary for medical reasons.
Those who are diagnosed with MGUS will be offered genetic analysis of their blood at DeCode (Íslensk erfðagreining), where the nucleic acids (DNA) will be isolated and analyzed for genetic variants. Plasma cells will be isolated from bone marrow samples for genetic and flow cytometry analysis. A part of the sample will also be sent to our study partner, Dr. Ola Landgren at the Memorial Sloan Kettering Cancer Center in the U.S. for further research. This will include gene expression profiling and other molecular measuring processes, which is done in order to study in further detail the differences between individuals as regards behavior patterns and attributes in MGUS and to gain deeper insight into the onset and progression of the condition. All samples sent abroad will be labelled with encrypted research numbers and are not, therefore, personally identifiable.
Further research could add to our knowledge of certain aspects of MGUS. This is why participants in the study are asked to allow their biosamples to be kept and used in further research. Such research could improve the accuracy of the diagnosis of MGUS in the future and will hopefully lead to improvements in treatment. Biosamples collected during this study will therefore be stored without any personally identifiable features. They will be stored in the Biosample Archive at DeCode (Íslensk erfðagreining). If the samples are transferred to another facility for storing or for research purposes, they cannot, therefore, be traced to you and the researchers will not have any access to personally identifiable information. If you consent, your tissue samples will be stored for 15 years after the end of the study. Further use will at all times be subject to permission from the National Bioethics Committee, and information on studies will be posted on the project’s website. Participants can request that their data be exempt from use in particular studies by contacting the investigators by e-mail or letter.
All participants will be asked to participate in a quality-of-life survey, regardless of the results of the screening. The aim of the survey is to assess the impact of disease screening on quality of life, and participants will be asked to complete a short questionnaire. This will be done at the beginning of the study, again 6 months into the study, and annually thereafter. The questionnaire is intended to assess quality of life, based on the personal experience of participants.
Additional health data for the study participants will be gathered by connecting the study data to the following health databases: the Cancer Registry, the Icelandic Pharmaceutical Database, the Health Clinics Communication Registry, the Inpatient Registry, the electronic medical records at Landspítali, and the Causes of Death Registry. Information regarding the health of participants will thus be gathered both before and after their participation in the study.
Myeloma is a cancer of the bone marrow originating in cells of the immune system called plasma cells. Normally, these cells produce antibodies that play a vital role in the body’s defenses against infections. On average, around 25 Icelanders are diagnosed with myeloma each year. The disease causes various adverse health effects, ranging from kidney disease to bone fractures. Due to great progress in the treatment of myeloma in recent years, the prognosis of patients with myeloma has improved significantly.
Monoclonal gammopathy of undetermined significant (MGUS) is the precursor to myeloma. This asymptomatic condition is characterized by the presence of certain abnormal proteins, called monoclonal antibodies, in the blood. MGUS is not a cancer, and most people with this condition never develop myeloma. Treatment for this condition is therefore not recommended. About 1% of individuals with MGUS develop myeloma every year, and in Iceland, about 4–5% of the population over the age of 50 are estimated to have the condition.
Results of the study may benefit individuals diagnosed with MGUS in the future. In addition, important knowledge will be accumulated on the impact of screening and knowledge of MGUS on the quality of life.
Some participants may be diagnosed with myeloma and will be offered earlier treatment at Landspítali, University Hospital.
The risks to participants are minimal. Slight discomfort may result from blood and bone marrow sampling for those asked to take part in further studies.
If you choose not to participate, you do not need to do anything. You are not required to provide any explanation or sign any documents. That decision will not impact your access to health care in the future in any way whatsoever. If you wish to enter the study at a later date, you can do so, and similarly, if you do decide to take part in the study, you can change your mind at any time and opt out.
Individual participants are medically insured according to local law in the same manner as everyone else. No special insurance covers this particular study, but study participants have the same legal rights as any other citizen.
Medical information regarding the participants in the study will be documented and stored in an electronic study registry. This information will be entirely non-personally identifiable. In order to make this information identifiable, a digital decoding key stored by the main research party is needed. After the end of the study, the information will be transferred to the planned database of medical information at Landspítali University Hospital.
Participation in the study will not cause you any expenses. No fees will be paid for participation in the study.
This study has been authorized by the Bioethics Committee, the Data Protection Authority, the Cancer Registry, the Directorate of Health, and the Chief Medical Officer at Landspítali University Hospital.
The study’s primary responsible party is Sigurður Yngvi Kristinsson, Professor at the University of Iceland (UI).
Other parties to the study are:
Þorvarður Jón Löve, Associate Professor at the Medical Faculty of UI
Andri S. Björnsson, Professor at the Psychology Faculty of UI
Ola Landgren, Professor at Memorial Sloan Kettering Hospital in the U.S.
Ísleifur Ólafsson, Head of Clinical Biochemistry and Laboratory at Landspítali University Hospital
Hlíf Steingrímsdóttir, Chief Executive of Medicine Services at Landspítali University Hospital
Kristinn Oddsson, Chief Physician and President of the Cancer Society
Tinna Laufey Ásgeirsdóttir, Professor of Economics at the University of Iceland
The Icelandic Heart Association (Hjartavernd)
Ásbjörn Jónsson, Head Department of Radiology at UI Hospital
Brynjar Viðarsson, Haematologist at UI Hospital
Páll Torfi Önundarson, Professor and Head of Laboratory Haematology at UI Hospital
Bjarni Agnarsson, Professor and Pathologist at UI Hospital
Margrét Sigurðardóttir, Pathologist at UI Hospital
Ragnar Danielsen, Cardiologist
Runólfur Pálsson, Head of Nephrology Department at UI Hospital
Ólafur Skúli Indriðason, Nephrologist at UI Hospital
Einar Stefán Björnsson, Professor and Head of Internal Medicine at UI Hospital
Ingunn Þorsteinsdóttir, sérfræðilæknir, Department of Clinical Chemistry at Landspítali University Hospital
Anna Margrét Halldórsdóttir, Senior Medical Officer at The Icelandic Blood Bank
Sveinn Guðmundsson, Director at The Icelandic Blood Bank
Ólafur Eysteinn Sigurjónsson, Professor
Elías Eyþórsson, MD and PhD student
Sæmundur Rögnvaldsson, PhD Student
DeCode (Íslensk erfðagreining)
The Icelandic Cancer Society
Binding Site in the United Kingdom
Icelandic Heart Association.
If you decide to participate in the study, you will be asked to grant your informed consent electronically on the website www.blodskimun.is by entering your personal identification number (kennitala) and the password that was sent to you in a purple envelope or by using an e-certificate or “Íslykill.” You can also grant your consent by signing the consent form that you should have received by mail in a purple envelope and mailing it back in the postage-paid envelope provided. No stamps are needed. You can opt out of the study at any time during the study period by sending an e-mail to firstname.lastname@example.org or by mail to the responsible party.
If you have further questions regarding your rights as a participant in a scientific study or wish to opt out of the study, you can address such questions to the Bioethics Committee, Borgartún 21, Reykjavík. Telephone number: +354 551-7100, e-mail: email@example.com.
If additional questions regarding the study arise, you can consult your doctor or obtain further information on the study website, by e-mail to firstname.lastname@example.org or by calling +354 896-0022.
On behalf of the study team
Sigurður Yngvi Kristinsson
Professor of Hematology
Faculty of Medicine of the University of Iceland