Drugs, older people and doctors; well-being or suffering? A simple list helps to avoid harm and to gain benefits

Dr Martin Wehling is Professor of Clinical Pharmacology at the University of Heidelberg. He is a board certified internist with expertise in cell physiology, steroid pharmacology, nongenomic steroid actions, clinical trials and clinical medicine. He discusses his Age & Ageing Paper VALFORTA: a randomised trial to validate the FORTA (Fit fOR The Aged) classification.

Drug therapy is the most relevant therapeutic intervention in medicine; older people tend to suffer from multiple diseases (multimorbidity) and thus are likely to receive multiple drug treatments (polypharmacy). It has been demonstrated that patients aged 65 and older take five or more drugs in 44% (male) and 57% (female) of cases and 10 or more drugs in 12% of cases.

Taking 10 and more drugs is unpredictable and expensive and seems to cause more harm than good, given that up to 100,000 deaths in the United States annually are attributed to medications. Guidelines are considered as main drivers of therapeutic decisions under the conditions of evidence-based medicine (EBM). As evidence for drug treatment in the older people is generally lacking (they are not liked in clinical trials as they get sick or die thereby spoiling the trial), applying EBM-guidelines to older people without supportive data results in experimental drug application often causing more harm than benefit. Though more clinical trial data are ultimately required, they will not solve the problem of disease-driven differences between individuals which rises sharply with age; this problem cannot be addressed by guidelines (or millions of them would be required), but by individualization of treatment.

One of the first formal attempts to improve drug safety despite this lack of study data in the aged population was the establishment of criteria for drugs to be avoided by Beers in 1997, which was lastly updated in 2015. The evidence for the clinical effectiveness of the Beers list is not compelling; the correlation of adverse effects with the presence of listed drugs is not firmly established. The other shortcoming of the Beers approach as the first example for a negative list is that an important aspect remains uncovered, namely, that there should also be a positive labelling of drugs that are indispensable in older people as data on morbidity, mortality, and safety are available or emerging for this particular treatment group. Although still insufficient in major therapeutic areas at present, there is increasing clinical evidence for beneficial action of, for example, blood pressure lowering drugs (e.g., Systolic Hypertension in Europe Trial, Hypertension in the Very Elderly Trial) or lipid-lowering agents (e.g., Prospective Study of Pravastatin in the Elderly at Risk Trial) in older people.

The FORTA (“Fit fOR The Aged”) classification is the first listing approach which provides both positive and negative labeling of commonly used medications for chronic illnesses (FORTA list). According to FORTA, medications belong to: Class A= (Absolutely): indispensable drug, clear-cut benefit; Class B= (Beneficial): proven efficacy but with safety concerns; Class C= (Careful): questionable efficacy/safety profiles, to be avoided or omitted when many other drugs are prescribed, review alternatives; or Class D= (Don’t): avoid in the elderly, omit first, review alternatives. The FORTA list has been developed as a clinical tool and currently provides 230 drug entries for 20 relevant diagnoses.

The instrument was now tested in over 400 hospitalized older patients[1] half of whom were subject to standard geriatric treatment; the other half was randomized to receive a FORTA-guided intervention.  The application of FORTA improves medication quality as measured by the FORTA-score; this new score sums up individual treatment errors of overtreatment (no disease for the drug, or drug in suboptimal FORTA class) and undertreatment (disease not treated or not treated by best available drug). It was improved by 2.5fold in the FORTA compared to the standard treatment group at very high significance. This is reflected in clinical outcomes which are very important to the patient: side effects of drugs were significantly reduced; one needs to treat only 5 patients to avoid one side effect. The study also showed that the FORTA principle and list can easily be introduced into clinical reality and teaching it to doctors is not difficult.

The typical use of the FORTA scheme would address general practitioners who receive multiple medication advices from different medical specialities for their patients; this is sometimes termed “additive medicine”. They would then synthesize the recommendations into a rank order of drugs that they could—with some rational judgment on top of the scheme—use to cut the list short. If important drugs are lacking, they would add important drugs known to really help older people. All this can be done within 10-15 min which seems to be not too much time to be spent on a challenging, complex older patient who otherwise may cause more trouble and consume more time due to complications.

The outcome is a medication scheme that is optimized and individualized to meet the requirements of older people by both avoiding harmful drugs, but also ensuring their participation in the great benefits of a growing number of drugs known to help older people. Its application requires knowledge on the patient to be treated as an individual, but comes with the charm of simplicity.

The FORTA list is being updated, a comparison of European FORTA lists for several countries is under way, and further clinical tests are planned to further support the usefulness of this new principle in other clinical settings e.g. in general practices or nursing homes.

[1] Wehling, M., Burkhardt, H., Kuhn-Thiel, A., Pazan, F., Throm, C., Weiss, C., Frohnhofen, H.

VALFORTA: a randomized trial to validate the FORTA (Fit fOR The Aged) classification.

Age Ageing Jan 18, 2016, doi: 10.1093/ageing/afv200 [Epub ahead of print]