MS trials: Do you SCUBA?*


[*seriously consider using bothersome acronyms]

Two decades ago, an alarm was sounded on the exploding use of acronyms in clinical trials. The worst offender at the time was cardiology, which boasted 16 separate trials called HEART (Fred et al. Tex Heart Inst J 2003;30:255-257). With acronyms on the radar, other specialties soon joined in. Within a few years, the estimated prevalence of trial acronyms was 15% (40% in cardiology) (Pottegard et al. Br Med J 2014;349:g7092). For some it filled a GAP (Greater Acceptance by Publishers): studies with good acronyms were more likely to be cited by other researchers (Stanbrook et al. N Engl J Med 2006;355:101-2).

Multiple sclerosis missed the first wave of acronymophilia. Initially, researchers did not name their trials or, in some cases, even themselves (IFNB Multiple Sclerosis Study Group, The Canadian Cooperative Multiple Sclerosis Study Group). Avonex opted for an abbreviation (MSCRG) rather than an acronym. Copaxone was a portmanteau (copolymer + axone) but for its trial it too eschewed acronyms (and MRIs).

Acronyms arguably began with the phase III Rebif trial, which sneakily inserted its results into its moniker (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis, or PRISMS). CIS trials then set the tone. Some were aspirational (CHAMPS) or vaguely neurological (REFLEX) and neatly teed up extensions (CHAMPIONS, REFLEXION), later seen with SELECT/SELECTION (daclizumab).

Other hopeful-sounding names soon followed: SENTINEL (natalizumab), FREEDOMS and TRANSFORMS (fingolimod), CARE-MS (alemtuzumab), ADVANCE (PEG-interferon) and EXPAND (siponimod). Some were a statement of intent, such as AFFIRM (natalizumab), CLARITY (cladribine), DEFINE/CONFIRM/ENDORSE (dimethyl fumarate), and STRATEGY (natalizumab to DMF switch). DEFINE was cheekily followed by REDEFINE, meant to show the ease of autoinjector use, which may have been a swipe at oral therapies.

Other studies, for no apparent reason, adopted a theme, such as music (OPERA, ORATORIO for ocrelizumab, ARPEGGIO and ALLEGRO for laquinimod), light (RADIANCE and SUNBEAM for ozanimod), or ancient history and mythology (HERMES and OLYMPUS for rituximab, ATON for atacicept, ASCLEPIOS for ofatumumab). Teriflunomide struggled with T words (TEMSO, TENERE, TOWER, TOPIC) before cobbling together acronym-adjacent names (TERI-PRO, TERI-RADAR).

High marks go to the vitamin D study called SOLAR (for Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment). However, it suffers from what Pottegard and colleagues call the Tolstoy manoeuvre: pretty much any acronym is possible if the name of the study is long enough. SOLAR also cast shade on an actual UV study, which had to settle for the low lumen AusD.

A few trials made curious choices. The cannabinol studies were a little spacy (SAVANT for THC/CBD, CUPID for dronabinol). The Avonex pen study (SFERA, perhaps referring to the ballpoint on a pen [penna a sfera] or a crystal ball [sfera di cristallo]), was unnecessarily obscure. The SABA trial of frankincense in RRMS may have borrowed its name from the Queen of Sheba, aka Saba. The TOTEM trial of testosterone was a little Freudian (although not taboo). In contrast, the untitled sildenafil study could well have profited from an acronym (VIMS?).

Some namings acquired a certain irony when the study failed, as with ACCLAIM (abatacept), CHOICE (daclizumab), the PPMS trials ASCEND (natalizumab) and INFORMS (fingolimod), and MS-SMART, which proved not so much.

Perhaps the most bizarre trial name was GOLEMS (Gilenya [FingOLimod] in prescribing conditions defined by the CzEch regulator of drug reiMburSement) study, an apparent borrowing from Jewish folklore. We can now wait for the SHEMS discontinuation study which, according to legend, will deactivate GOLEMS.

More problematic is when a trial makes an apparent claim, a trend that began with BENEFIT (Betaseron) and continued with BECOME (Betaseron vs. GA), EVIDENCE (Rebif vs. Avonex), ENABLE (fampridine), ENHANCE (fampridine again), RELIEF (Rebif at night), RENEW (mitoxantrone), REVEAL (natalizumab vs. fingolimod), RESTORE (natalizumab re-initiation) and RESPOND (GA to DMF switch). Perhaps the most egregious example was HALT-MS (Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis), sponsored by the NIH, which should have known better.

A concern is that trial names that make a PROMISE (as in GA for PPMS) create expectations and may be a source of bias for patients and researchers. As some authors have noted, it may be coercive to offer a patient a place in a trial called CURE, HOPE or SAVED (Orlowski et al. Chest 2002;121:2023-2028). Who could refuse? In their analysis, the authors found that 6.5% of trial acronyms were probably or almost certainly coercive; they suggested that IRBs should put a stop to suggestive trial names.

A more fanciful problem is that at the current rate of acronym use, the English language will run out of acronym-appropriate words by 2028, according to one estimate (Nusbaum et al. J Med Humanit 2009;30:131-133). But switching to another language will be a challenge: will the REMYELINISIERUNG trialists be able to recruit enough words to satisfy the acronymic requirements?

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