Below are the most likely reasons why your request was rejected:
- Factor concentrate population pharmacokinetic model is unavailable for the specified brand and/or measurement assay type (clotting vs. chromogenic). While we have models for most brands, there are some not available. We continually work to increase the number of factor concentrate specific models in WAPPS. Please continue to submit cases if you have as they will be useful for modeling.
- Baseline or endogenous factor concentrate activity is unlikely. For severe patients and most clinical laboratories, the baseline value is < 0.01 IU/ml (<1%) as the assays used to measure factor concentrate activities usually have a limit of quantification (LOQ) of 0.01 IU/ml. Sometimes, the LOQ is lower but is almost never below 0.004 IU/mL (0.4%). Baselines that are input as equal to a value below 0.004 IU/ml, will be rejected. Make sure you input 0.01 IU/ml for baseline only for moderate patients with that very value. For severe patients, it usually is <0.01 IU/mL. If the patient is actually severe (i.e. <0.01 IU/ml) but you forget the “<”, this has enormous implications for the outcome of the clinical calculator. For example, if the baseline is input as 0.01 IU/ml and the clinician uses the clinical calculator to determine what dose will achieve a trough of 0.01 IU/ml, the dose will be 0 because the patient was reported as having an endogenous activity of 0.01 IU/ml.
- If baseline is missing, it will be set to <0.01 IU/mL.
- Post-infusion sample activities are input as lower than the provided baseline activity. It is impossible to have a measurement lower than the endogenous activity. Please change the baseline activity or the measurements accordingly.
- The population PK model is unable to produce reasonable estimates of half-life, time to 2% etc. We compare the outcome of the individual assessment against what we know about PK from the underlying population. When the individual PK is far from what we know of the population, there is great uncertainty in the estimates and sometimes we will reject based on this.
- Input errors are common (e.g. height is input as 1.7 cm and not 170 cm; activities increase over time) and lead to rejections
- If only one post-infusion sample is entered and no prior infusion dosing information is input, the estimates may be too uncertain to allow the use of the calculator, which has been inactivated. The addition of prior infusion information, especially when linked with a sampled pre-dose activity, greatly increases the precision and certainty of the resulting individual PK.
- Prior infusion data do not match the pre-dose measurement. For example, if the pre-dose SHL activity is input as 0.05 IU/ml, the previous infusion is set at 48 hours and then a 24-hour post activity measurement of 0.05 IU/ml is provided, there has very likely been an input error.