16 November 2022: Haemovigilance & Pharmacovigilance Panel - C

Post-lunchbreak, the topics shifted away from HV directly, to the matter of people giving consent to a transfusion or being informed after the event if they were incapacitated. Counsel went to the NICE guidelines. It was agreed that the inclusions therein about providing verbal and written information to explain reasons, risks, and the process involved were accurate. They also had to be in the correct format for the patient/carer. Sometimes putting an explanation in the wider context is difficult under certain clinical circumstances. There is also the issue of residual risk, and the fact of having had a transfusion continuing to be a consideration in future assessments. A SaBTO document was displayed which echoed the content of the NICE statement. It went further to include the need to ensure the information was included in the hospital discharge summary so that the patient and their GP had a note. The hope is that it becomes part of the permanent record. The SaBTO document went on to mention training on the issue of consent starting from the undergraduate stage in training, with updates at least three-yearly.

It was reported that regionally there is only 9% compliance on applying the transfusion consent responsibility, with national compliance being at 26%. This was described by the panel as disappointing but not unsurprising. “It is a challenge to get standards into practice”, it was stated, and that was not just for blood safety. Work is ongoing, and while it is not a SaBTO responsibility, they do draw attention to it. The Chair picked out the difficulties the witnesses had highlighted prior to the lunchbreak, which are made worse by this non-compliance. It was noted that the new guidelines do tend towards giving patients a lot of information, maybe too much for some. It would not be good if consent information got lost in that. There is more work to be done on presenting information to patients.

Counsel asked about the proposal for a transfusion database to be established, this being distinct from a patient record, but rather a central resource. This was seen to be very useful. It would also bring huge public safety benefits. It would be best to integrate it into the overall NHS electronic systems and make it UK-wide since so many patients move around. It could help with the root cause analysis exercises. There would be value if it could be linked to outcomes (with anonymity assured). Such a database would bring greater transparency and would increase quality and length of life. A transfusion database would also help in dealing with PV, too. On the possibility of a database, it might need to be a stand-alone system which was able to extract information from other systems. It would take considerable political will, investment, and cultural change to actually happen. Part of the resistance would relate to concerns over data security. It would also require better compliance by people recording transfusion information.

More particularly for PV issues, it was reviewed how products are licenced, and how issues are raised; including through the Yellow Card Scheme. When required, a major safety review can be carried out as part of PV. The benefit-risk approach was reviewed from the MHRA listing of factors to consider. This is applied to new drugs and ones being marketed with new safety signals, since when the use of a drug expands that requires a way to ensure potentially new adverse events are picked up. It is part of the need to achieve continuous surveillance. It was noted that a clinical trial is a very controlled environment, whereas once a drug goes out to the public, new circumstances apply that would not have been encountered in the trial. That relates to latent events, too. When required, manufacturers may have to go back and do more work on a potential risk issue prior to full or renewed licencing.

Counsel introduced the hypothetical situation of a product which may have infection risks, but the benefits of the drug were considered to outweigh the possible problems. The panel said it would require a very careful study into the risks. There would be efforts to have a way to mitigate if the risk materialised. Some drugs are only available to certain cohorts of people where a risk is considered not material. Continuing the hypothetical case, and when the risk profile changed over time, that would involve gathering as much data as possible and speaking with independent specialists. If the risk could not be eliminated, the product would be expected to be removed. A public assessment report would be expected to be involved. The aim would be to release as much information as possible to let people see why decisions were being made.

It was recognised how there was greater understanding of infectious agents, not least affected by much greater travel by the population. Risks with blood are constantly changing, whereas for drugs there is greater control of the change factors because there is a set starting point. For blood, it is considered safe, but there are still risks, so matters of consent require a balanced approach.

A second hypothetical case was presented by Counsel, that of a new blood-borne virus (BBV) entering the blood supply. Understanding would initially be scant, but as time moved on the risks were increasingly evident. However, there might be resistance to limiting blood use despite the risks. The panel immediately went to Covid to help answer the question. It was recognised how it would be a huge interest to the panel and their organisations due to the vigilance aspects involved. There isn’t hard evidence for a new BBV emerging, but it was considered likely. Initially, Covid infectees were not to donate blood until it was understood their infectivity through that route. The last time something similar was looked at was with vCJD. The panel said they would look for a pattern emerging, which would be helped by the proposed transfusion database. They were not confident that the current reporting systems would be able to cope with the scenario. It was seen to reflect on the recent childhood hepatitis cases. There would be factors in the response to do with the microbiological profile of the virus.

Prior to Covid, there had been an expectation of a respiratory viral outbreak. The JPAC response was fast. For a new BBV, quick decisions would need to be made about deferring donors and seeking a testing regimen. Means such as donor selection, leukodepletion processes, and testing the blood are the three main strategies for blood. There would be worries about new generation sequencing and looking at checking the infectiousness and transmissibility characteristics of the virus. Covid demonstrated the speed of moving forward with new treatments, “if there’s a will to do it”. A new BBV is a worry, particularly due to the unknowns. Since there are limits on how to respond, it will be essential to maintain a high level of vigilance.

Asked about the robustness of the current arrangements to deal with something like a new BBV, clearly, there would be considerations such as the scale of the risk, bit certainly they would move quickly to remove suspected products from use. Work would concentrate on where the virus had entered the supply chain. Other regulatory bodies would be alerted, including internationally to share intelligence. Effective communication would also be essential. There would be early efforts to bring together any specialists who might have information to contribute, not least to interrogate their agency’s thinking and proposed approaches. The data being used to inform decisions would be made public. The agencies would work well together, as this has been demonstrated to happen in urgent situations. The aim which is shared by all, is that of patient safety. Wider collaborations would include the universities and industry. Data source sharing was very effective during Covid, including on the emerging intelligence on the vaccines and how different ways of rolling these out made a difference. The WHO has a massive database. However, it was noted that recently the international collaboration on Covid was waning.

The willingness of people, including two of the panel, to give up their time freely to support agencies such as those represented, was seen as incredibly important. The same applies to the independent experts they work with. Their involvement can be considerable. The fact they are not employees but are in the field using the products and treating people is vital. There is a concern about their employing organisation becoming less willing to allow their staff to be involved due to the time and effort involved. The concern was that it would reduce access to the best people to support the work. But rather than simply paying people, the suggestion was to pay their employing organisation. Recognising people for their voluntary offering was important, but not necessarily by paying them directly. Paying organisations allows people to justify the time they spend, and to have the chance to put in the required effort for the agency they are supporting. That includes both the well established experts and the rising stars. It was suggested that a central fund could be created to pay the employers who allow their staff to be involved. 

The issue of the cost of achieving “marginal gains” was raised. A case where the cost of achieving a particular benefit/gain was very high was used as an extreme example. At some point a decision has to be made about how small a gain might be before spending lots of money on it becomes intolerable, either for the public purse on one hand or the public pressure on the other. Health economists need to help Ministers make decision just like clinical bodies such as SaBTO do. Effectively, they advise while the Minister has to decide. On these types of cases the minutes of meetings are still made public since ultimately it is the public to decide who and what they prioritise spending on, then they expect the Governments they elect to do accordingly. Paid-for health intervention produce two basic outcomes, living longer and having a better quality of life.

Counsel then invited each panel member to summarise what they saw as the weaknesses in the current system of HV and PV. One response was the freedom and robustness of the incident reporting service. Reporters sometimes feel pressure not to paint a negative picture of the place where they work. It is seen as connecting to the overall cultural change issue. There are human elements, software not updated, a new piece of kit. One of these alone might produce a near miss situation, but line them up and a real harm may be the result. Another suggested weakness was the complexity of the whole HV system itself, including examples of duplication or overlap. A third suggestion was the need to simplify reporting, and mention was made of the concept of “conditional logic”. More artificial intelligence and machine learning is helping to simplify things. There is also the opportunity to allow patients to report reactions to blood component use. The way patients describe things is different from the way clinicians refer to things. For PV, there is the need to better understand the biological mechanisms involved.