Suggested procedures for supporting accurate response evaluation: HI-E
| Item . | Suggested IWG 2018 procedures . | IWG 2006 procedures . |
|---|---|---|
| Baseline assessment procedures | ||
| Screening period for the evaluation of transfusion burden and baseline Hb levels* | 16 wk but only in lower-risk MDSs, when anemia is the predominant or only cytopenia; patients should be off any active treatment during this period | 8 wk |
| Transfusions: Patients with unusual or abnormal changes of their transfusion rate during the 16-wk observation period should be evaluated carefully for confounding factors (ie, bleeding, hemolysis, EPO levels, iron metabolism), including a potential extension of the evaluation period | ||
| Baseline Hb: For the determination of the baseline Hb level, we suggest using the mean of all available Hb measurements during the 16-wk screening period; to avoid bias, measurements prior to transfusions should be used in this calculation for TD patients and the measurements should be at least 7 d apart | ||
| No./frequency of Hb measurements prior therapy | Hb measurements for the determination of baseline Hb values should be performed (or retrospective results should be available) at least every 2 wk, if possible, during the 16 wk screening period | NA |
| Blood count device/method and laboratory | Investigators should be aware of potential fluctuations in Hb measurements due to different blood count devices or laboratories | NA |
| To avoid any ambiguities in Hb levels, investigators should check when using several devices/methods or laboratories whether they yield similar Hb levels; in case of different values, baseline Hb level (as well as subsequent response and response duration) should be assessed based on measurements from only 1 device/method or laboratory, especially at key time points of a clinical trial | ||
| Baseline Hb level | Hb < 10 g/dL as prerequisite for patients in need of therapy | Hb < 11 g/dL |
| Response evaluation procedures | ||
| Response evaluation period | 24 wk | 8 wk |
| No./frequency of Hb measurements | Hb measurement should be performed (or results be available) at least every 2 wk during the first 16 wk of therapy | NA |
| Blood count device/method and laboratory | Investigators should be aware of potential fluctuations in Hb measurements due to different blood count devices or laboratories | NA |
| To avoid any ambiguities in Hb levels, investigators should check when using several devices/methods or laboratories whether they yield similar Hb levels; in case of different values, baseline Hb level, response, and response duration should be assessed based on measurements from only 1 device/method or laboratory, especially at key time points of a clinical trial | ||
| Dose adjustment policy for high Hb levels | Treatment should be continued at a lower dose level (ie, increased intervals between doses or administration of lower dose level) rather than stopped when 2 subsequent Hb measurements exceed a predefined threshold | NA |
| If the drug under investigation is being reduced in dose, stopped, or its administration delayed in a responding patient for protocol-defined reasons leading to a loss of response, this should not be counted as such, if reintroduction of the drug at the same or lower dose induces a new response | ||
| If the reintroduction of the drug at a lower dose does not reinduce a response, this should be documented as such | ||
| When the investigational drug is being reduced in dose, stopped, or its administration delayed, blood counts are required continuously to monitor subsequent blood levels |
| Item . | Suggested IWG 2018 procedures . | IWG 2006 procedures . |
|---|---|---|
| Baseline assessment procedures | ||
| Screening period for the evaluation of transfusion burden and baseline Hb levels* | 16 wk but only in lower-risk MDSs, when anemia is the predominant or only cytopenia; patients should be off any active treatment during this period | 8 wk |
| Transfusions: Patients with unusual or abnormal changes of their transfusion rate during the 16-wk observation period should be evaluated carefully for confounding factors (ie, bleeding, hemolysis, EPO levels, iron metabolism), including a potential extension of the evaluation period | ||
| Baseline Hb: For the determination of the baseline Hb level, we suggest using the mean of all available Hb measurements during the 16-wk screening period; to avoid bias, measurements prior to transfusions should be used in this calculation for TD patients and the measurements should be at least 7 d apart | ||
| No./frequency of Hb measurements prior therapy | Hb measurements for the determination of baseline Hb values should be performed (or retrospective results should be available) at least every 2 wk, if possible, during the 16 wk screening period | NA |
| Blood count device/method and laboratory | Investigators should be aware of potential fluctuations in Hb measurements due to different blood count devices or laboratories | NA |
| To avoid any ambiguities in Hb levels, investigators should check when using several devices/methods or laboratories whether they yield similar Hb levels; in case of different values, baseline Hb level (as well as subsequent response and response duration) should be assessed based on measurements from only 1 device/method or laboratory, especially at key time points of a clinical trial | ||
| Baseline Hb level | Hb < 10 g/dL as prerequisite for patients in need of therapy | Hb < 11 g/dL |
| Response evaluation procedures | ||
| Response evaluation period | 24 wk | 8 wk |
| No./frequency of Hb measurements | Hb measurement should be performed (or results be available) at least every 2 wk during the first 16 wk of therapy | NA |
| Blood count device/method and laboratory | Investigators should be aware of potential fluctuations in Hb measurements due to different blood count devices or laboratories | NA |
| To avoid any ambiguities in Hb levels, investigators should check when using several devices/methods or laboratories whether they yield similar Hb levels; in case of different values, baseline Hb level, response, and response duration should be assessed based on measurements from only 1 device/method or laboratory, especially at key time points of a clinical trial | ||
| Dose adjustment policy for high Hb levels | Treatment should be continued at a lower dose level (ie, increased intervals between doses or administration of lower dose level) rather than stopped when 2 subsequent Hb measurements exceed a predefined threshold | NA |
| If the drug under investigation is being reduced in dose, stopped, or its administration delayed in a responding patient for protocol-defined reasons leading to a loss of response, this should not be counted as such, if reintroduction of the drug at the same or lower dose induces a new response | ||
| If the reintroduction of the drug at a lower dose does not reinduce a response, this should be documented as such | ||
| When the investigational drug is being reduced in dose, stopped, or its administration delayed, blood counts are required continuously to monitor subsequent blood levels |
NA, not available.
The 16-wk screening period applies mainly to lower-risk MDSs where anemia is the major cytopenia. Patients with higher-risk MDSs or with severe thrombocytopenia may require earlier treatment and an 8-wk screening period is acceptable in that situation.