The Views of Healthcare Professionals, Drug Developers and Regulators on Information about Older People Needed for Rational Drug Prescription

<div><p>Background</p><p>The ICH E7 guideline intends to improve the knowledge about medicines in geriatric patients. As a legislative document, it might not reflect the needs of healthcare professionals. This study investigated what information healthcare professionals, regulatory agencies and pharmaceutical industries consider necessary for rational drug prescribing to older individuals.</p><p>Methods and Findings</p><p>A 29-item-questionnaire was composed, considering the representation in trials, pharmacokinetics, efficacy, safety, and convenience of use in older individuals, with space for additions. Forty-three European professionals with an interest in medication for older individuals were included. In order to investigate their relevance, five items were included in a second questionnaire, with 11 control items. Median scores, differences between clinical and non-clinical respondents and response consistency were analysed. Consistency was present in 10 control items. Therefore, all items of the first questionnaire and the five additional items were analysed. Thirty-seven (86%) respondents returned the first questionnaire; 31/37 (84%) the second. Information about age-related differences in adverse events, locomotor effects, drug-disease interactions, dosing instructions, and information about the proportion of included 65+ patients was considered necessary by most respondents. Clinicians considered information significantly more important than the non-clinical respondents about the inclusion of 75+, time-until-benefit in older people, anticholinergic effects, drug-disease interactions, and convenience of use. Main study limitations are the focus on information for daily practice, while the ICH E7 guideline is a legislative document focused on market approval of a new medicine. Also, a questionnaire with a Likert scale has its limitations; this was addressed by providing space for comments.</p><p>Conclusions</p><p>This study reveals that items considered necessary are currently not included in the ICH E7 guideline. Also, clinicians’ and non-clinicians’ opinions differed significantly in 15% of the items. Therefore, all stakeholders should collaborate to improve the availability of information for the rational prescribing to older individuals.</p></div

Gender, specialty, and working country of the respondents.

*<p>Internist, nursing home physician.</p

Differences in scores between clinical and non-clinical respondents.

*<p>Items of the second questionnaire.</p

Determinants of adherence with dosing guideline.

<p>Determinants of adherence with dosing guideline.</p

Adherence with the Dutch dosing guideline.

<p>---- = no dosage adjustment required</p><p>n.a. = not applicable</p><p>* = contra-indicated drug in case of MDRD < 30 ml/min/1.73m²</p><p>** = contra-indicated drug in case of MDRD ≤ 50 ml/min/1.73m²</p><p>Al. tract and metabol. = alimentary tract and metabolism</p><p>Antiinf. for syst. use = antiinfectives for systemic use</p><p>Adherence with the Dutch dosing guideline.</p

List of the 41 analysed medications.

<p>List of the 41 analysed medications.</p

Flowchart of inclusion.

<p>Flowchart of inclusion.</p

Oral medicines in the Paediatric Investigation Plans (n = 150 PIPs); group wise comparison.

<p>*a preparation is a subtype of a dosage form in a particular strength and with a particular excipient composition e.g. a PIP containing film-coated tablets 50 mg and chewable tablets 5, 10 and 20 mg represents one overall dosage form (tablets), two tablet subtype dosage forms (film-coated tablets and chewable tablets) and four preparations (film-coated tablets 50 mg, chewable tablets 5 mg, chewable tablets 10 mg, chewable tablets 20 mg).</p

Oral preparations in the PIPs per target age group.

<p>Oral preparations in the PIPs per target age group.</p

Tablet size and shape (n = 150 PIPs); group wise comparison children aged between 2 and 6 years.

<p>*tablets counted as the number of oral preparations i.e. differentiated to excipient composition and strength. A small tablet wa defined as 0–4 mm, medium sized 5–9 mm and large 10 mm or larger <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098348#pone.0098348-European8" target="_blank">[21]</a>. Oval tablets included those that were oblong or capsule shaped.</p>&<p>related to the two tablets sized 10 mm or larger.</p