This is an app useable on all mobiles, tablets and desktops that calculates the immunoglobulin dose to administer, taking into account the ideal body mass (IBM) adjustment recommended in the NHS England Updated Commissioning Policy for the use of therapeutic immunoglobulin (Ig) (December 2021).
When an administrator user is logged in, their gravitar and name appear here. This allows editing of the disease indication database.
When an administrator user is logged in, they can enter new diseases into the disease indication database by completing all the below fields and clickig save.
An administrator can edit existing indications on the database. This form is reached by expanding an indication on the right hand panel and clicking "Edit Disease" at the bottom of the section.
This is a list of all the indications for immunoglobulin therapy as well as indications that were considered and rejected by the NHS England Commissioners. Click on the inverted triangle next to an indication name to see detailed information about the indication, specifically a description of the disease, the speciality it falls under (to aid in searching through the list), the eligibility criteria for immunoglobulin, the Demand Management priority colour code, the recommended dose regimen usually in g/kg, the outcome measures to enter in the National database and the Commissioning Category (including whether or not prior permission from the subregional panel is required).
Click the item next to "Sort by" to select how to sort the indications in the database; each click cycles through the sort criteria. The options are:
"Default": the order they appear in the database
"ABC": alphabetical order
"Speciality": grouped according to their speciality
"Demand Management Priority": grouped from highest to lowest priority
"Dose regimen": roughly lowest to highest dose requirement
"Commissioning": grouped from highest to lowest commissioning status
An administrator can edit or delete the entire indication from here.
This is a brief description of the disease considered to be an indication for immunoglobulin treatment. There may be greater detail presented here for some grey and non-commissioned indications to aid in individual funding request (IFR) applications to the national IFR panel and potential subregional immunoglobulin assessment panel (SRIAP) support of such applications.
This is simply a convenient means to help find a certain indication for immunoglobulin.
Eligibility criteria are taken from NHS England's Immunoglobulin Commissioning Policy (December 2021). The two categories are:
Commissioned without prior approval (generally conditions requiring urgent treatment where there is no equally good alternative management)
Those that require prior subregional immunoglobulin assessment panel (SRIAP) approval
For indications not specified in the current guideline, criteria are determined from previous NHS England guidelines that listed them as grey indications or from a brief review of the limited literature on immunoglobulin's efficacy.
The Demand Management Priority system has been superceded by the new commissioning criteria (Immunoglobulin Commissioning Policy, Dec 2021). However, in situations of short supply, the red and blue priorities could still be applied. Note that there is no longer a grey priority. These indications were either switched to commissioned (blue or red) or are simply no longer commissioned. I have made them blue indications if there are considered to be equally effective alternative treatments, red if not. I have kept former left and right hand grey legacy indications to aid in IFR request prioritisation. Note that demand management prioritiy is separate from prior SRIAP approval requirement; an indication could be red because there is no equivalent alternative but require prior approval because it is generally non-urgent or there might be some decision making around dosing or management strategy:
"Red": defined as indications where there may be no other good alternative treatment, these are therefore the highest priority indications where there is short supply.
"Blue": indications with good evidence for efficacy, but there are alternative treatments available that may be as effective.
"Grey": indications where there was formally limited, if any, evidence for efficacy. These are the lowest priority indications in circumstances of short supply.
"Black": indications where there was positive evidence that immunoglobulin is not effective. IFR applications should not normally be sought for such indications.
"Unlisted": this is an indication that has never been considered by NHS England or the Department of Health in regard to its suitability fo immunoglobulin treatment. It might be added onto this database because of previous national IFR panel applications made with support of the subregional panel.
The commissioning criteria (Immunoglobulin Commissioning Policy, Dec 2021) describe the recommended dosages and regimens for each indication. Other indications do not have these speficied in all cases so typical regimens are taken from the literature of from previous commissioning guidance.
It is now no longer considered necessary to check for IgA deficiency before administration in routine as well as in urgent indications (Immunoglobulin Commissioning Guidelines V1.3, Feb 2019).
Blood tests should be performed on day 1 and on day 3 of administration to check for haemolysis (FBC, blood film and unconjugated bilirubin).
Ig may have prothrombotic risks which patients on long term therapy should be counselled about, and prevention measures should be addressed as in DVT prevention guidelines.
While many regimens of 2 g/kg can be administered in as few as 2 split daily doses, note that in certain conditions, due to autonomic instability, the 2 g/kg dose must always be split over 5 days.
As described in the NHS England Commissioning Policy, the dose in adults is rounded down to the nearest whole vial. Since 5 g vials are normally available the App rounds down to the nearest 5 g multiple. Splitting of doses into daily amounts is done using whole vials. The dose need not be exactly the same each day. In children the dose should be by ideal body weight only; where the calculated dose is less than 15g, the dose is made up using 5g and 2g vials.
In long term use, many indications (especially in neurology) should incorporate a treatment reduction plan. The dosing frequency should be set to the relapse time after the first short term dose, or extended up to 3 months if no relapse between the first and second short term doses. Once a dosing interval has been determined, the dose should be incrementally reduced by 20% (of the initial dose) until there is reduced response and then set to the dose just above this thereafter.
For commissioned indications, the new commissioning criteria (Immunoglobulin Commissioning Policy, Dec 2021) lists the outcome measures that are expected to be entered on the national database. For other indications, previous Department of Health guidelines (c.f. 2011) are used. The outcome measures are not specified for most other indications so they have been instead determined based on review of the limited literature.
For some indications, there will be some choice re outcome measures to be used depending on the individual patient. Since many require before and after treatment measurements, these measures must be decided upon and taken before treatment. It is therefore expected that the form submitted to pharmacy will include the outcome measures being used and the pre-treatment results. There must be a plan for recording the post-treatment outcome around 2-4 weeks after treatment and commuicating this to pharmacy for entry on the database.
Note that for some indications, e.g. in immunology, the IgG level must be measured as a baseline before treatment; this is because monitoring of its change determines further management.
In most situations, long term treatment requires annual review. When a request for a repeat course is made of pharmacy, the time of last review should be checked. If a review is due, this is communicated to the clinician if review data have not been submitted with the request. If this information is not provided by the time of the next course, that course of immunoglobulin may not be dispensed until the information is forthcoming.
The nature of long-term annual review might take the following forms:
Delay next course until relapse, record outcome measures on relapse and compare with the most recent peak treatment outcome scores, and with a subsequent outcome score following the next treatment.
Record outcome measures again to confirm that the improved scores following a previous course compared with pre-treatment scores have been maintained.
Note that the commissioning policy points out that in certain conditions, most notably CIDP and inflammatory myopathies, spontaneous stabilisation is common and so the first of the above methods of long term review (i.e. trial withdrawal) should be used on at least 2-3 occasions.
Most established indications for immunoglobulin therapy are commissioned directly by NHS England. The rules for whether commissioning consent needs to be obtained in advance by a subregional Immunoglobulin Panel (SRIAP) acting on behalf of NHS England have been clarified for each indication:
Prior panel permission not required. This is because treatment is standard and often clinically urgent.
Prior panel permission not required (emergency list). These are conditions that normally require prior permission because there are considered to be equally effective alternative treatments. However, it was recognised that in some of these conditions patients might suffer harm because of the potential delay. Hence many regions have agreed and drawn up "exception" lists of emergency indications.
This emergency list is based on the draft local list for the North-East London Subregional Panel v0.4 (Jun 2019), in some cases made obsolete by changes in the commissioning policy (Dec 2021).
Prior panel permission required. These are conditions that require prior permission because there are considered to be equally effective alternative treatments. However, these other treatments may be associated with side effects that prevent usage or may take several weeks to work, e.g. rituximab. Therefore there is a vital role for Ig in initial stabilisation, e.g. in myasthenic crisis or dysphagia or respiratory failure in inflammatory myopathy. The prior permission of the local immunoglobulin panel or of the subregional immunoglobulin panal is required before the immunoglobulin can be dispensed. If Ig is for short term stabilisation, a parallel long term treatment plan with immunosuppression may be expected by the panel. This submission is normally managed by pharmacy using the information provided by clinicians. There may be some days' delay before a decision is reached, usually requiring recommendation by two panel members and sign-off by the Chair or Deputy Chair. If a clinician considers the decision must be made more urgently than this, see below.
Not commissioned and requires IFR (former left-hand Grey indication). This is a legacy category. Left-hand grey indications had sparse evidence for efficacy and were previously commissioned. On commissioning review in 2021, left-hand grey indications were switched either to commissioned or not commissioned. However, for indications that are now not commissioned it may nevertheless be helpful for IFR applicants and SRIAPs to know how they were formally considered.
Not commissioned and requires IFR (former right-hand Grey indication). This is a legacy category. Right-hand grey indications had no good evidence for efficacy and were not commissioned. It may be helpful for IFR applicants and SRIAPs to know how they were formally considered.
Not commissioned and requires IFR (unlisted). This would be an indication that has never been considered by NHS commissioning, i.e. neither a former grey indication, nor a former black indication where clear evidence of no benefit. It is possible that they may receive a commissioning status in future updates based on new evidence. However, immunoglobulin is not currently commissioned for such indications. Nevertheless, exceptionality may be more easy to justify to an IFR team than a former grey indication that has actively been switched to non-commisioned status, presumably on the basis of new negative evidence or lack of positive evidence.
Shown to be ineffective (Black indication).These are indications listed as 'Black' in previous NHS England guidance based on clear evidence that immunoglobulin is ineffective for this indication. Immunoglobulin will not be commissioned for this indication.
The procedure for making an IFR request to the NHS England IFR team would be to make a draft written submission first to the Subregional Immunoglobulin Assessment Panel (SRIAP). In the submission, it would need to be demonstrated that the patient i) fits the indication specified, ii) fits the eligibility criteria if published, iii) has had their pre-treatment outcome measures recorded, iv) has an evidence-based justification for requiring this treatment as opposed to being given any other standard treatment for their condition. There may be a rescinding of the temporary "waiver" on requirement for exceptionality that may have applied to former right-hand grey indications on the basis that the commissioners had not had the opportunity to consider new evidence that became available after the previous guidance of 2011. Grounds for exceptionality might be that the case is i) an indication with a rare sub-type not properly considered by NHS England when drawing up its policy in 2021, or ii) that the condition itself has never been considered by NHS England, or iii) for a right-hand grey indication, there is compelling new evidence since 2021 of the efficacy of immunoglobulin compared to other treatments. The SRIAP will review draft submissions, and may offer advice to optimise submissions or offer support for submissions where appropriate. Again, it might be hard to justify an IFR when the commissioning policy has specifically switched an indication from grey to non commissioned.
With any indication requiring prior approval or not commissioned, if a clinician considers the decision must be made more urgently than the panel can achieve, they would follow the Trust's procedure for prescribing and dispensing urgent non-formulary medicines (typically local Drugs and Therapeutics committee Chair's action). The information detailed above for IFR submissions should be provided to the Trust. It should be made very clear that the patient i) fits the indication specified, ii) fits the eligibility criteria if published, iii) has had their pre-treatment outcome measures recorded, iv) has a justification for requiring this treatment urgently as opposed to being given any other standard treatment for their condition in the time frame. The clinician's department would bear responsibility for its cost if no IFR submission is made within one month after administration of the Ig, of if it is made in time and rejected by the National IFR Panel.
The clinician should first consider the likelihood of acceptance before requesting a decision to treat, for example, an indication where the commissioning policy has listed the status as black or specifically switched the status from grey to non commissioned.
Enter the patient's sex, whether they are a child, their height and mass. Sex and mass is not required in children; height determines their IBW.
Height is needed to determine if the patient's actual mass is significantly greater than their ideal body mass. The latter is calculated according to the Robinson formula (J. D. Robinson, 1983, converted to metric):
Man: 52 kg + 0.75 kg per cm height over 152 cm
Woman: 49 kg + 0.67 kg per cm height over 152 cm
In children an adult IBW formula is clearly inappropriate. The Devine formula, for example, which is similar to the Robinson formula, was found to overestimate IBW by over 6 kg in larger children and by over 8 g in smaller children, when compared with the McLaren method which uses the 50% centile mass for a child of particular height and age (Kang et al, 2019). The McLaren method is similar to the Moore method listed in the UK Medicines Information document on "How should medicines be dosed in chldren who are obese", which is referenced by the NHS Commissioning Policy. In contrast, the Traub formula underestimated mass in a sample of 1-3 year olds by just 0.3 kg overall, and 0.26 kg in the smallest 5% of children in the sample and 0.2 kg in the tallest children. In 3 to 17 year olds, it underestimated mass by 0.66 kg overall, 0.56 in the smallest 5% and 0.62 in the tallest 5%. Rather than resort to height and weight charts, this formula is therefore used and it does not require the child's age:
IBW (kg) = 2.396 x e^(0.01863 x height (cm))
Note that in children, unlike adults, no correction for obesity is used as stated in the commissioning policy.
In some circumstances it may not be possible to enter an indication, or there may be a specific reason to calculate a dose from a g/kg dosage. Entering the dosage here will calculate the dose to give based on ideal body weight.
Make sure no indication is selected in the Indications drop-down box above by clicking the blank row at the top of the list of indications, or clicking Calculate will default to using the selected indication.
If you wish to enter a regimen manually, either a single dose in g/kg or a dose range (e.g. 0.5 to 1.5 g/kg), rather than using the unlisted dosage box to the left, typing it here will usually yield a conversion into actual doses by parsing the text field. Please delete the entry here, if you wish to calculate a listed indication dose or use the unlisted dosage box.
Make sure no indication is selected in the Indications drop-down box above by clicking the blank row at the top of the list of indications, or clicking Calculate will default to using the selected indication.
Clicking this button calculates the total immunoglobulin dose to administer. If the actual body mass is > 20% more than ideal body mass (IBM), the mass to be used to calculate Ig dose will be adjusted according to the formula (use kg):
Corrected mass = IBM + 0.4(actual mass – IBM)
This is version 0.3 of the Ig Calculator application.
Changes from version 0.2:
Changes from version 0.1: