Post-marketing surveillance (PMS) of new drugs is imperative to quantify common adverse drug reactions and to identify rare adverse reactions. The whole ethos of drug safety monitoring or ‘pharmacovigilance’ as it is known today, came into being through the tragedy of thalidomide.
This disaster of the early 1960s produced an estimated 10,000 deformed babies in the countries in which the drug thalidomide was widely used in early pregnancy. This disaster led directly to the establishment in Europe of the modern drug regulatory mechanisms. In the UK these mechanisms were first enacted into law by the Medicines Act, 1968. Even before this Act was implemented it was officially recognised that no drug which is pharmacologically effective is entirely without hazard and not all hazards can be known before a drug is marketed.
Following the thalidomide tragedy, a Committee on Safety of Drugs was established, later renamed the Commission on Human Medicines (CHM). Its task was to identify problems relating to pharmaceutical substances, to assess their toxicity and report the findings to prescribers and patients. The CHM today monitors adverse drug reactions (ADRs) by way of a spontaneous reporting mechanism known as the ‘Yellow Card’ scheme managed by the Medicines and Healthcare products Regulatory Agency (MHRA), the UK licensing authority.
DSRU established in 1980
Formerly known as the Drug Surveillance Research Unit, the Drug Safety Research Unit (DSRU) was founded in 1980 by Professor William Inman, one of the earliest contributors to post marketing surveillance and the person responsible for developing the yellow card system. Although spontaneous reporting systems have many real advantages, he recognised their limitations and as a result Professor Inman established the DSRU and devised a method for the early detection of potential drug hazards known as Prescription-Event Monitoring (PEM), which he based on ‘Event Monitoring’ (Finney D.J. The design and logic of a monitor of drug use. J. Chron. Dis. 1965, 18:77). Initially, having received an initial grant from the Office of the Chief Scientist together with unconditional pledges from the pharmaceutical industry, the DSRU was part of the Faculty of Medicine at the University of Southampton. However in 1986, it was reconstituted as a registered independent charity (No. 327206), changing its name to Drug Safety Research Unit because of the emotive connotation of the word ‘surveillance’.
DSRU no longer conducts PEM studies
In the late 1990s, a new version of PEM was developed, known as Modified PEM, or M-PEM, which enabled greater flexibility in the data requested from prescribers. Standard PEM studies were gradually phased out over the subsequent decade, such that the DSRU now conducts M-PEM studies, but not standard PEM studies. In 2009 the methodology was further modified to allow studies to be conducted in secondary care using Specialist Cohort Event Monitoring (SCEM).
The DSRU now operates as an Associated Department of the School of Pharmacy and Biomedical Sciences at the University of Portsmouth. The unit has run training courses in pharmacovigilance since 2000, under the auspices of DSRU Education and Research Ltd. A postgraduate programme in Pharmacovigilance, offered in association with the University of Portsmouth, was launched in September 2010.
There is a particular irony in that the building the DSRU inhabits today, Bursledon Hall, was once a children’s hospital where some of the worst cases of thalidomide were cared for in order to provide parental respite.
Our house and its grounds was previously known, in the early 19th century, as Brixedone and formed part of a much larger privately owned estate. Between 1935 and 1940, the estate belonged to the Thistlethwayte family of whom, many surviving Southampton residents of the second world war years, hold fond memories.
During the first weekend of September 1940, intensive bombing of Southampton docks saw families fleeing for safe refuge and, on hearing this, the Thistlethwayte’s ventured out in their cars to rescue as many as possible and bring them back to Brixedone for shelter. Whenever possible, each family occupied their own room, with everybody sharing the large kitchen. Food was supplied by the Ministry of Food for the period that they were there until other accommodation was found for them.
Soon after, Brixedone was taken over by the Royal Marines who remained in occupancy until some time after the war. In 1948, the Thistlethwayte’s sold the entire estate which included a farm and approximately 400 acres up river. The latter is better known today as the Upper River Hamble Country Park. The main house and immediate grounds including a cottage, comprising approximately five acres, was sold to the Southampton and South West Hampshire Health Authority and became Bursledon Children’s Hospital.
In 1989, the hospital was purchased by the Drug Safety Research Unit at which point it became Bursledon Hall.
The DSRU is an independent academic unit that monitors, studies and communicates the safety of medicines in order to protect the public from untoward and unwanted side-effects of new medicines. As a registered independent medical charity, our aim is to achieve the highest possible scientific and ethical standards, by putting the interests of patients first and to work with integrity and fairness with all our collaborators.
Through the continued support of GPs in England and in partnership with hospital specialists, we investigate the unwanted adverse effects of newly marketed medicines by monitoring patients during the early life of a new medicine. In addition, we participate in publicly funded research and development projects initiated by the European Commission under the VII Framework Programme.
Professor William Inman FRCP, FFCM
The DSRU was founded by Professor W.H.W Inman in 1980. ‘Bill’ Inman battled against polio from his early days as a medical student in Cambridge in 1950 and qualified as a doctor despite the confines of his wheelchair. Bill was the first medical student to complete his studies entirely at Addenbrooke’s Hospital. In 1959 while at ICI trying to run clinical trials, he met the late Sir Derek Dunlop, first chairman of the DHSS’s Committee on Safety of Drugs. In 1964, he was recruited as a founding member of the permanent staff of the committee, later to be renamed the Committee on Safety of Medicines (CSM). His role was Medical Assessor of Adverse Reactions.
1966 saw him pioneer the first study which linked the Pill with thrombosis. Four years later, he showed that the dose of hormones could be reduced, increasing safety without reducing efficacy. This earned him the accolade ‘ Father of the mini-pill’.
Bill Inman developed the ‘yellow card’ scheme in which GPs are voluntarily invited to report their suspicions about drug hazards. In 1980, he was seconded to the University of Southampton by the DHSS through Sir Douglas Black, former president of the Royal College of Physicians who was at that time the DHSS’s Chief Scientist. He was to develop a more sophisticated and sensitive mechanism in order to monitor the safety of newly marketed drugs. He was appointed to the world’s first chair of Pharmacoepidemiology, the scientific study of drug safety and efficacy.
Being aware of the limitations of spontaneous reporting and influenced by the work of the eminent statistician, David Finney, Bill Inman established a system for Prescription-Event Monitoring (PEM) to monitor events of any suspected causality by the GPs. PEM was established with support from the eminent physicians of the time including Sir Richard Doll, and later became affectionately known as the Green Card system. For the 25 to 30 years that PEM existed in the UK in its original form, it was the envy of the world in relation to the collaboration with thousands of GPs in England who contribute information free of charge.