TABLE 1.
Research questions and summary of results of the GRADE‐ADOLOPMENT process and decision for recommendations.
| Chapter | Guideline review question | Topic | Included in NICE guideline | Systematic reviews (SRs) | Randomised controlled trials (RCTs) | ADOLOPMENT decision |
|---|---|---|---|---|---|---|
| 1. Disease‐modifying therapies | What is the effectiveness of disease‐modifying pharmacotherapies in people with ALS and related syndromes? | Riluzole | Yes | 1 Cochrane SR (Miller 2012 22 ) | 4 RCTs included in Cochrane SR (Bensimon 1994 23 , Bensimon 2002 24 , Lacomblez 1996 25 , Yanagisawa 1996 26 ) | Use Cochrane review |
| Edaravone | No | — | 3 RCTs (Abe 2014 27 , Abe 2017a 28 , Abe 2017b 29 ) | New review | ||
| Cell‐based therapies | No | 1 Cochrane SR (Abdul Wahid 2019 30 ) |
2 RCTs included in Abdul Wahid 2019 30 (Gothelf 2017/Berry 2019 31 , Oh 2018 32 ) 4 new RCTs (Amirzagar 2015 33 , Cudkowicz 2022 34 , Duning 2011 35 , Nefussy 2010 36 ) |
Update Cochrane review | ||
| AMX0035 | No | — | 1 RCT (Paganoni 2020 [CENTAUR] 37 ) | New review | ||
| Tofersen | No | — | 1 RCT (Miller 2022 [VALOR] 38 ) | New review | ||
| 2. Service delivery | What is the effectiveness of coordinated ALS clinic‐based multidisciplinary care (MDT) versus standard care by local neurologist in people with ALS and related syndromes? | MDTs | Yes | — | — | Adapt NICE recommendations |
| 3. Management of communication | What is the effectiveness of interventions for communication problems in people with ALS and related syndromes? | Communication | Yes | — | — | Adapt NICE recommendations |
| 4. Management of nutrition | What is the effectiveness of interventions for malnutrition in people with ALS and related syndromes? |
Management of malnutrition |
Partially – timing of gastrostomy | — |
4 RCTs (Dorst 2022 [TOLCAL‐ALS Study] 39 , Ludolph 2020 [LIPCAL‐ALS] 40 , Wang 2022 41 , Wills 2014 42 ) |
Dietary interventions: new review Swallowing therapy, enteral feeding, parenteral feeding: empty reviews [consensus‐based recommendations] |
| 5. Management of respiratory symptoms | What is the effectiveness of interventions for weak cough in people with ALS and related syndromes? | Weak cough | Yes | — | — | Adapt NICE recommendations |
| What is the effectiveness of interventions for thick mucus in people with ALS and related syndromes? | Thick mucus | Yes | — | — | Adapt NICE recommendations | |
| What is the effectiveness of interventions for respiratory insufficiency in people with ALS and related syndromes? | Respiratory insufficiency | Partially – pharmacological treatments only | 2 Cochrane SRs (Maguire, unpublished, Raduvic 2017 43 ) |
3 RCTs included in Maguire (ND) (Gonzalez‐Bermejo 2016 [RespiStimALS] 44 , McDermott 2016 [DIPALS] 45 , Katz 2017 [NEALS]) 2 RCTs included in Raduvonic 2017 (Bourke 2006 46 , Jacobs 2016 47 ) |
Use Cochrane review for NIV and diaphragmatic pacing Consensus‐based recommendations for IV (empty review) Adapt NICE recommendations for pharmacological interventions |
|
| 6. Management of other symptoms | What is the effectiveness of interventions for muscle weakness in people with ALS and related syndromes? | Muscle weakness | Yes | — | — | Adapt NICE recommendations |
| What is the effectiveness of pharmacological interventions muscle cramps in people with ALS and related syndromes? | Muscle cramps | Yes | 1 Cochrane review (Balendra, unpublished) | 4 RCTs included in Balendra (ND) (Oskarsson 2018 48 , Weber 2010 49 , Weiss 2016 50 , Weiss 2021 51 ) |
Use Cochrane SR (unpublished update) |
|
| What is the effectiveness of pharmacological and physical therapy interventions for spasticity in people with ALS and related syndromes? | Spasticity | Yes | 1 Cochrane review (Asworth 2012 52 ) |
1 RCT included in Asworth 2013 (Drory 2001 53 ) 1 new RCT (Riva 2019 54 ) |
Update Cochrane SR | |
| What is the effectiveness of pharmacological and non‐pharmacological interventions for musculoskeletal pain in people with ALS and related syndromes? | Musculoskeletal pain | No | — | 1 RCT (Riva 2019 54 ) | New review | |
| What is the effectiveness of interventions for sialorrhea in people with ALS and related syndromes? | Sialorrhea | Yes | 1 Cochrane SR (James 2022 55 ) | — | Use Cochrane SR | |
| What is the effectiveness of pharmacological interventions for emotional lability in people with ALS and related syndromes? | Emotional lability | No | — | 3 RCTs (Brooks 2004 56 , Pioro 2010 57 , Smith 2017 58 ) | New review | |
| What is the effectiveness of pharmacological and non‐pharmacological interventions for fatigue in people with ALS and related syndromes? | Fatigue | No | — | 1 RCT (van Groenestijn 2019 59 ) | New review | |
| What is the effectiveness of interventions for constipation in people with ALS and related syndromes? | Constipation | No | — | — |
Empty review [consensus‐based recommendations] |
|
| What is the effectiveness of interventions for hoarse voice and laryngospasm in people with ALS and related syndromes? | Hoarse voice and laryngospasm | No | — | — |
Empty review [consensus‐based recommendations] |
|
| What is the effectiveness of pharmacological and non‐pharmacological interventions for insomnia in people with ALS and related syndromes? | Insomnia | No | — | — |
Empty review [consensus‐based recommendations] |
|
| 7. Psychological and emotional support | What is the effectiveness of pharmacological and non‐pharmacological interventions in people with ALS and related syndromes? | Anxiety | Partially (psychological support, not specific about anxiety) | — | — |
Empty review [consensus‐based recommendations] |
| Depression | Partially (psychological support, not specific about depression) | — | — |
Empty review [consensus‐based recommendations] |
||
| 8. Prevention of deep vein thrombosis | What is the effectiveness of pharmacological and non‐pharmacological intervention for primary prevention of DVT in in people with ALS and related syndromes? | Deep vein thrombosis (DVT) | No | — | — |
Empty review [consensus‐based recommendations] |
| 9. End of life | What is the best method for planning of end of life in people with ALS and related syndromes? | Provision of end‐of‐life care | Yes | — | — | Adapt NICE recommendations |