Thursday, 2 October 2014

Study of Children Harmed by Medicines finds Doctors Fail to Listen

Report on Adverse Drug Reactions in Children reveals

better communication needed between doctors and patients

Of 5118 children admitted to Europe's largest children's hospital between 1 October 2009 and 30 September 2010, 17.7% experienced at least one adverse drug reaction (ADR), according to a new report.

The Adverse Drug Reactions in Children (ADRIC) report, was funded by the National Institute for Health Research and is the first large-scale and long-term study of its kind to report on the ADRs of children under hospital care.

The aim of the research that took place in the largest children’s hospital in Europe, Alder Hey Children’s Hospital, is to improve the safety of medicines administered to those under 16. Many common medicines are licensed without being tested on children thoroughly, if at all, yet are used regularly in paediatric healthcare.

Drug safety in paediatric care is a neglected area of research. Most medicines go through drug trials using primarily adult samples. In 2006, 75% of all 317 European centrally licensed drugs were relevant and used for children yet only half of these had indications, or validated medical reasons, for child use. This means a large proportion of drugs used for children are ‘off-label and/or unlicensed’ (OLUL). These have not undergone thorough trials to gain evidence for calculating appropriate dosage and efficacy in children of different ages. It is therefore difficult to evaluate the risk-benefit ratio for the children taking OLUL drugs, therefore increasing the risk of ADRs.

Simple extrapolation of pharmaceutical data for adult to child use is inappropriate, given the size differences in children that would alter optimal dosages as well as the developmental changes in a child’s physiology that could affect responsiveness to a drug.

The ADRIC study discovered 31% of acute children’s emergency admissions to hospital were attributable to OLUL drugs. Perhaps unsurprisingly these drugs were also found significantly more likely to be implicated in ADRs than for drugs licensed for children.

Drugs most commonly implicated in admissions were cytotoxic agents, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) vaccines and immunosuppressant drugs. Adverse side-effects from medication taken at home accounted for 3% of admissions to the Alder Hey Children’s Hospital, where the reaction was the main reason or contributed to the reason of their visit. Of the reactions, one-fifth was found to be either definitely or possibly avoidable. In most cases, it was found these would have been prevented if not for oversights by the doctor of previous ADRs to the same drug, insufficient patient education of possible ADRs, and prescribing that could have been more rational, with possible use of alternative drugs.

Nearly 20% of children and young people who had been inpatients at the hospital for over two days suffered at least one ADR from treatment during their stay. Opiate analgesics and general anaesthetic (GA) drugs were found responsible for over half the cases of ADRs in this group. General anaesthetic drugs presented a hazard to patients six times as high as any other drug administered to patients. Of the ADRs reported, 1% of these resulted in permanent harm or a higher level of care being required for the patient.
With few exceptions, parents reported poor management and communication from their clinicians about suspected ADRs. Reports described parents receiving inadequate or contradictory information from doctors about their child’s medical assessments. One parent described how “no-one actually said why it [the hallucination] was happening, the nurses just thought it was a bit funny”; others felt “fobbed off” by clinicians or even “lied to” when doctors could not explain their child’s ADR to them.
When there was an improvement in communication, it was when parents were more anxious. At these points parents reported a greater level of information from clinicians as compared to other times. When less anxious and therefore better placed to absorb facts, information received was “little or none”.  Reports from parents gave a sense information was conveyed only when it was pushed for.
The study observed a consequence of poor doctor-patient communication is the potential for missing out certain symptoms, such as hallucinations, anxiety, nausea and pain which can be described only by the patient verbally. It is possible that this explains the under-representation of ADRs of this type reported in younger children and those mentally disabled, than in adults.
The study looked at current methods of ADR identification and reporting. At present, the Yellow Card reporting scheme allows patients and relatives to report suspected or confirmed ADRs. These are sent to the MHRA, a regulatory board for pharmaceutical use in the UK. This scheme was reported to be relatively unheard of by patients, however when informed, the idea was much favoured by the parent and patient population as an essential tool for reporting ADRs.
Positively, the report found that parents, children and young people work on the same principles as doctors when evaluating the possibility of an ADR over an unrelated symptom, recommending them as equally reliable sources of detection. So, rather than being “ignored” and “dismissed”, the report’s findings recommend that patient and parental concerns ought to be taken more seriously by clinicians, with greater trust and emphasis put on patient self-evaluation.
With these changes taken on board, the ADRIC report believes the greater recognition and improved recording of ADRs could reduce the incidence of avoidable harm to patients from prescribed medicines and anaesthetics.  

References: Smyth RL, Peak M, Turner MA, Nunn AJ, Williamson PR, Young B, et al. ADRIC: Adverse Drug Reactions In Children a programme of research using mixed methods. Programme Grants Appl Res 2014;2(3)

Jacqueline Bond 02/10/14

Jacqueline is a graduate from Oxford University having read Psychology, Philosophy & Physiology, and a Masters in Neuroscience from Imperial College London. She is doing research for APRIL and contributes to the APRIL blog.

Added note from Millie Kieve, formerly chair of Advisory Group to Evaluation of Patient Yellow Card Reporting:

I wish to thank Jacqueline Bond for her careful review of the 200-page ADRIC report about the adverse drug reactions of children in hospital. The full report can be found here:

I was involved with a study to evaluate the value of patient reporting in 2011, also funded by the The National Institute for Health Research (2). The researchers concluded  “patient reporting of suspected ADRs has the potential to add value to pharmacovigilance by reporting types of drugs and reactions different from those reported by Health Care Professionals.”
In regards to the low awareness of Yellow Card reporting of adverse drug reactions (ADRs), we have made multiple requests to the Medicines Healthcare Products Regulatory Agency (MHRA) to increase publicity and their availability. APRIL believes Yellow Cards and awareness of the Yellow Card system of pharmacovigilance is not well publicised.
Healthcare Professionals do not have a good record for reporting ADRs and those other than doctors have had to persuade, in the past, the regulatory body to accept their reports as valid. The official assessment of less than 10% of serious ADRs reports is a reflection of the poor awareness and promotion of the scheme.
We have requested that posters and YC cards be displayed in hospitals, doctors’ surgeries and in community and supermarket pharmacies. The lack of visible encouragement for patients, pharmacists, nurses and doctors to report ADRs raises the question of why this essential method of monitoring the safety of medicines is currently under-publicised.
Pharmacovigilance in the UK should be improved to increase awareness of the extent of iatrogenic (treatment-induced) injuries to mental and physical health. Hospital admissions caused by ADRs has been estimated to cost the NHS £466 million annually (1).

References to note

1)     Stage Three: Directive. Improving medication, error incident reporting and learning - 20 March 2014 MHRA Study NHS/PSA/D/2014/005

2)    Evaluation of patient reporting of adverse drug reactions to the UK Yellow Card Scheme

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