Table 3 Summary table of key issues by therapeutic area

 Hypertension

Aliskiren/amlodipine

Aliskiren is recommended within clinical guidelines both as monotherapy and in combination with other antihypertensives. However, the fixed combination of aliskiren and amlodipine that was appraised by the G-BA is not covered within the guidelines

 Postoperative management of cataract surgery

Bromfenac

Guidelines suggest the therapeutic class (NSAID) in the perioperative period in cataract surgery, but do not specify any medicine

 Glaucoma

Tafluprost/timolol

Guidelines strongly support the use of preservative-free medicines if there is evidence that patients are allergic to the preservative, but do not specify any medicine

 Diabetes

Canagliflozin

Canagliflozin/metformin

Linagliptine

Lixisenatide

Vildagliptine

Vildagliptine/metformin

Guidelines evolved over time. While metformin remains the gold standard for initial drug therapy, guidelines support other classes and products such as canagliflozin and its class (SGLT-2 inhibitors), linagliptin and vildagliptin (DPP-4 inhibitors), and lixisenatide and its class (GLP-1 agonists) i) as monotherapy (SGLT-2 and DPP-4 inhibitors) in patients who are not eligible for initial metformin treatment and ii) as combination therapy (SGLT-2 and DPP-4 inhibitors and GLP-1 agonists)

Insulin degludec

Basal insulin analogues are recommended within guidelines. Within that class, insulin degludec is one option

 Hypercholesterolemia

Lomitapide

Lomitapide and other new therapeutic options are part of the suggested treatment algorithm in patients with homozygous familiar hypercholesterolemia

 Irritable bowel syndrome

Linaclotide

Only one updated guideline is available [28]. This guideline recommends linaclotide as second-line treatment if previous laxatives did not help and patients had constipations for at least 12 months

 Schizophrenia

Lurasidone

Guidelines generally recommend second generation antipsychotic drugs, but the evidence base for appropriate comparisons is considered limited

 Dupuytren’s contracture

Microbial collagenase

Lack of relevant guidelines for the treatment of Dupuytren’s contracture

 Overactive bladder

Mirabegron

Guidelines evolved over time and included mirabegron as second-line treatment [31]

 Epilepsy

Perampanel

Guidelines are heterogeneous [44] and partially not updated, e.g. the American Epilepsy Society is still presenting a 2004 publication on their homepage as guidance for refractory epilepsy.

Retigabine

Retigabine is recommended as adjunctive second line treatment [32]

 Colorectal carcinoma

Regorafenib

Regorafenib is recommended both in US and EU clinical guidelines [33] as second/third line of therapy.

 Gastrointestinal stromal tumor

Regorafenib

Regorafenib is recommended as second/third line of therapy [34]

 Prostate cancer

Sipuleucel-T

Sipuleucel-T is recommended by various guidelines in patients with metastatic prostate cancer and asymptomatic or minimally symptomatic disease

 Hyperphosphatemia

Colestilan

Guidelines generally recommend phosphate binding agents but do not specify any medicine

 Hypolactasia^a

Gaxilose

No relevant guidelines were identified for hypolactasia.

 Wound healing

Living larvae from Lucilia sericata

Only one guideline from 2012 is available [35]. Living larvae considered superior versus hydrogel therapy in terms of wound cleansing