Appropriateness of Oral Drugs for Long-term Treatment of Lower Urinary Tract Symptoms in Older Persons

Results of a Systematic Literature Review and International Consensus Validation Process (LUTS-FORTA 2014)

Matthias Oelke; Klaus Becher; David Castro-Diaz; Emmanuel Chartier-Kastler; Mike Kirby; Adrianwagg; Martinwehling

Disclosures

Age Ageing. 2015;44(5):745-755. 

In This Article

Methods

Procedure

The present expert rating procedure evolved from a previous conference during which the situation of older people with urinary incontinence was evaluated.[14] The procedure was performed in the following steps:

  • Identification of the rater team members: The initiators of the project (M.W. and M.O.) identified raters based on available information on the internet. Experts were eligible if they met the following criteria: geriatric internists/geriatricians, general practitioners or urologists with documented clinical experience in the pharmacotherapy of (multimorbid) older people; high academic status; prominent standing in the leading geriatric/urological medical associations; substantial number, quality and relevance of publications. Accordingly, five raters (K.B., D.C., E.C.K., M.K., A.W.) were identified who met those criteria and could also accept the invitation to participate.

  • Selection of drugs to be assessed: In the first step, the initiators M.W. and M.O. selected groups of drugs used orally for long-term treatment of LUTS and listed relevant agents in each group. Urological drugs were chosen if they are typically used as long-term treatment. Given this limitation, antibiotics drugs were not considered. The proposed choice of drugs was refined by the raters who voted for removing non-oral drugs (e.g. oestrogen ointment).

  • The relevant drug classes were 5α-reductase inhibitors, α1-blockers, antimuscarinics, β3-agonists and PDE5 inhibitors (Table 1). Medication codes using the WHO Drug Reference List, which employs the Anatomical Therapeutic Chemical (ATC) classification system, were added for completeness and to facilitate subsequent searches.

  • Systematic literature review: A literature search in PubMed/Medline and the Cochrane library was performed in March 2014 using the search terms [drug name] in the INN terminology plus the standard filters [clinical trials] [full text available] [age 65+ years], and [age 80+ years]. The aim of the search was to identify appropriate clinical trials to examine the efficacy, safety and tolerability of drugs used for the treatment of LUTS in older people. A total of 835 abstracts were retrieved and reviewed by M.W. and M.O. for appropriateness, in particular whether the article explicitly reported results in the age groups ≥65 years, ≥70 years, ≥75 years, ≥80 years, ≥85 years. In a second step, [drug name] and the terms [elderly] or [older] in the title were searched. In total, 62 additional abstracts were retrieved and checked for appropriateness. A duplicate article was removed. Analysis of studies as full texts: A total of 34 potentially appropriate articles were identified. They were reviewed as full texts and key information extracted by M.W. and M.O. into an extensive Microsoft Excel file with particular focus on the presence of information on particular side effects (see Supplementary data, Appendix S1, available in Age and Ageing online http://ageing.oxfordjournals.org/content/44/5/745/suppl/DC1). No attempt was made to contact authors to acquire additional data or unpublished data.

  • Analysis of summary of product characteristics: The most recent summary of product characteristics (SmPC) was downloaded for all drugs from the EMA website, or if not available, from other reliable sources (e.g. www.fachinfo.de). For generic drugs, the most frequently used brand was selected based on the prescription volume in Germany.[1] The texts were thoroughly analysed by M.W. and M.O. using the same template as for the full texts above. From this material, the initiators, M.W. and M.O. derived a proposal for initial FORTA labels. The proposal together with the spreadsheet and full texts/abstracts were forwarded to the rater team for review and addition of further articles that were felt to be relevant.

  • Two-step Delphi process: The initiators and members of the rater group convened at a meeting at the annual EAU congress in Stockholm on 15 April 2014 and were instructed by M.W. and M.O. about the process with particular focus on the FORTA procedure.

After the meeting, raters reviewed the literature and classified each of the listed drugs according to FORTA, together with optional comments. The related survey is deposited in the Supplementary data, Appendix S2, available in Age and Ageing online http://ageing.oxfordjournals.org/content/44/5/745/suppl/DC1; 16 drugs and 17 items were finally rated (low dose/extended release and standard dose/immediate release oxybutynin separately rated).

Statistics

Details of the Delphi method (all experts rate independently without knowing their peers' ratings, knowing only the reached consensus) and the corresponding statistical analysis have been described in detail previously.[12] In brief, the aggregated list of rater labels was statistically analysed (see below), the aggregate findings were sent out to the reviewers for a second rating round if the consensus coefficient was <0.800.

For this statistics, raters' FORTA labels were converted into numerical values A→1, B→2, C→3 and D→4, respectively; the mean (m) and mode were calculated for each item, reconverted to FORTA labels and compared with the original author-based labels. The range for each label was defined as:

if 1 ≤ m < 1.5 → FORTA Class A
if 1.5 ≤ m < 2.5 → FORTA Class B
if 2.5 ≤ m < 3.5 → FORTA Class C
if m ≥ 3.5 → FORTA Class AD

where m = mean based on the raters' Grades 1–4.

Consensus parameters were generated by calculating the percentage of experts' FORTA ratings (minus abstentions) in line with the original FORTA values, both overall and for each item separately. The coefficients were then corrected (cons_corr) to weight the degree of deviation between the experts' individual FORTA ratings, expressed in terms of range class, from 0 to 3 as defined:

Range = 0: unanimity among all experts (no deviation);
Range = 1: greatest range only from A to B or B to C, or C to D (neighbouring classes), ½ weight;
Range = 2: greatest distance from A to C or B to D, 2/3 weight;
Range = 3: greatest distance from A to D, full weight.

In the second round, as in the first procedure, values were converted and medians and means calculated. The arithmetic mean provided the basis for back conversion to FORTA labels that were compiled for all drugs in a separate, annotated list. After the second round, the Delphi process led to unequivocal results and was finished.

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