The safety and efficacy of pharmacotherapy can be measured in multiple ways during the different stages of a drug’s life cycle. Adverse drug reactions and medication errors are described in the data stored in the health care registers, enabling the retrospective research of the events. Research focusing on medication safety forms the basis for the effectiveness of individual therapies. This post starts a new series of featuring blog posts, called Safety from data. The writer of this post, Outi Laatikainen, works as a Scientific Advisor at Medaffcon and has vast previous experience in medication safety research in specialized health care.
When a drug creates an effect in the body, one can also always be on the lookout for a countereffect. The basis for this lies in physiology: many of the target receptors for medicine have more than one function in the body. Thus, changing any receptor function is always a balancing act between the wanted effect and different degrees of unwanted effects – the adverse effects.
As stated above, adverse drug reactions are literally unwanted effects, as their occurrence is obviously neither wanted nor intended. Accordingly, multiple mechanisms have successfully been developed to detect and prevent adverse reactions in advance, preferably even prior to the use of the drug.
Marketed drugs are safe and effective
Before access to the market, the safety and efficacy of a drug are ensured in multiple steps in both the drug development stage and while applying for marketing authorization, placing extremely high safety criteria for all marketed drugs.
In the drug development stage, the pharmacological efficacy and safety are examined in preclinical and clinical studies (phases I-III). Substances presenting any kind of toxicity or severe adverse reactions are eliminated early in the development process. Once the drug development is completed, the safety and efficacy of a new pharmaceutical product are assessed by national authorities before the drug is released for wider distribution to the public.
Phase IV – safety after marketing authorization
The safety surveillance is not limited to the stages preceding marketing authorization. The safety profile of a drug is supplemented with additional data on possible adverse events and medication errors throughout the drug’s life cycle (phase IV). Phase IV surveillance is set as an obligatory responsibility for both the holder of marketing authorization and the national medical surveillance authority – both of which execute this obligation actively.
Phase IV surveillance is an important part of medication safety work as, although highly comprehensive, there are certain limitations to the preclinical and clinical phase studies. Due to obvious restrictions to clinical trial study population size, the studies are conducted by gradually advancing from patient cohorts consisting of a few dozens to sample sizes of, at best, a few thousand. Additionally, elderly patients and patients with several comorbidities or polypharmacy are often excluded from the trials to reduce study bias.
Clinical trials are also often limited by their follow-up time. Thus, extremely rare adverse events and events that appear after lag-time or only in certain populations (due to e.g., specific metabolic characteristics) can remain undetected. It is common that these types of events only appear after wide distribution, i.e., once the drug is being marketed worldwide and used by a large number of patients.
Real-world evidence in medication safety
The occurrence of adverse drug events is constantly monitored by signal detection. In signal detection, every report on adverse drug reactions or medication errors constitutes as a signal that, along with other adverse event signals, can be used to assess drug safety on a population-wide level. However, voluntary reporting methods can only cover up to 5-10% of all adverse events as the events quite often tend to go undetected.
The developmental leaps in ICT and health care digitalization have introduced new methods also for medication safety surveillance. Currently, the description of adverse drug reactions and medication errors is stored in the electronic patient record data in the health care registers.
“Unlike clinical trials, RWE studies are conducted using data from clinical practice. Thus, health care registers provide a unique data source for medication safety research and surveillance.”
Health care registers provide a unique data source for medication safety research and surveillance in a real-world setting. From the data, adverse events detected in clinical trials can be analyzed in a clinical setting, enabling the assessment of their actual prevalence within the user population.
Using real-world data, it is possible to detect patient groups with a higher risk of severe adverse reactions. Thus, it is possible to target individual pharmacotherapies for patient populations that are less susceptible to adverse events, hence increasing the likelihood of improved outcomes for medication use. On the other hand, the real-world prevalence of adverse reactions can remove use restrictions for pharmacotherapies in the specific patient groups if the risk for adverse events in clinical practice appears significantly lower compared to that detected in the clinical trials.
Healthcare registers also contain information concerning medication errors, where patient harm can occur due to reasons that may be altogether independent of the drug’s pharmacological characteristics. Such events include errors in, for example, prescribing, dispensing, or administration of a drug, that can result in, e.g., administration of an inadequate dose or the use of an erroneous administration route. Especially with medication error research, real-world data provides unique possibilities as such errors are impossible to study during clinical trials.
AI in medication safety work
Methods utilizing artificial intelligence (AI) and machine learning have brought new and exciting prospects for the use of registered data in medication safety work. New, intelligent methods enable the expansion of research from known events to previously undetected adverse reactions, i.e., events that already affect the outcome of pharmacotherapy but which we are yet unable to detect due to the lack of analysis methods. The detection of new and less common adverse events with machine learning methods can further improve the prospects of pharmacotherapy in cases where the event is preventable.
Medication safety is an integral part of the overall efficacy of pharmaceutical care. If the treatment of patients is continuously discontinued due to adverse events, the treatment effectiveness will decrease or, in worst cases, even turn negative. Targeting individual pharmacotherapies to patients with a lower potential for adverse events results in improved treatment outcomes.
Health care registers are an endless source of safety signals for pharmacotherapies, the utilization of which is in the interest of all parties. At best, medication safety research can improve the understanding of medication safety in a way that enables the use of certain therapies in patient groups that would otherwise be left without treatment.
Currently, register studies rely on data that is readily available in a structured format. However, the majority of medication safety information is descriptive and, thus, unstructured. Until recent years, medication safety research has relied on manual research methods. Advances in method development in the analysis of unstructured data are needed and will most likely be seen in the near future.
The Safety from Data -series is a new, regular series featuring blog posts. You will get the opportunity to read more about registered data, medication safety, and RWE studies in the future Safety from Data -blog posts.