Evidence map›Paper›PMID 36060538›Full record

ReviewFrontiers in digital health2022

Appropriate controls for digital therapeutic clinical trials: A narrative review of control conditions in clinical trials of digital therapeutics (DTx) deploying psychosocial, cognitive, or behavioral content.

Jacqueline Lutz, Emanuela Offidani, Laura Taraboanta, Shaheen E Lakhan, Timothy R Campellone

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Frontiers in digital health, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 5 pooled it
11.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 5 syntheses or guidelines pooled it, 83 citations in OpenAlex.

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  16. Diving into the Regulatory Landscape of Digital Therapeutics.Therapeutic innovation & regulatory science · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Jacqueline LutzMedical Office, Click Therapeutics Inc., New York, NY, United States.
Emanuela OffidaniMedical Office, Click Therapeutics Inc., New York, NY, United States.
Laura TaraboantaMedical Office, Click Therapeutics Inc., New York, NY, United States.
Shaheen E LakhanMedical Office, Click Therapeutics Inc., New York, NY, United States.
Timothy R CampelloneMedical Office, Click Therapeutics Inc., New York, NY, United States.
Click Diagnostics (United States) · USCornell University · USVirginia Tech · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Digital therapeutics (DTx) are software programs that treat a disease or condition. Increasingly, DTx are part of medical care, and in the US healthcare system they are regulated by the FDA as Software as a Medical Device (SaMD). Randomized controlled trials (RCT) remain a key evidence generation step for most DTx. However, developing a unified approach to the design of appropriate control conditions has been a challenge for two main reasons: (1) inheriting control condition definitions from pharmacotherapy and medical device RCT that may not directly apply, and (2) challenges in establishing control conditions for psychosocial interventions that build the core of many DTx. In our critical review we summarize different approaches to control conditions and patient blinding in RCT evaluating DTx with psychosocial, cognitive or behavioral content. We identify control condition choices, ranging from very minimal digital controls to more complex and stringent digital applications that contain aspects of "fake" therapy, general wellness content or games. Our review of RCTs reveals room for improvement in describing and naming control conditions more consistently. We further discuss challenges in defining placebo controls for DTx and ways in which control choices may have a therapeutic effect. While no one-size-fits-all control conditions and study designs will apply to all DTx, we propose points to consider for defining appropriate digital control conditions. At the same time, given the rapid iterative development and optimization of DTx, treatments with low risk profile may be evaluated with minimal digital controls followed by extensive real-world effectiveness trials.

Indexed as

control conditionsdigital clinical trialsdigital healthmHealthplacebo controlpsychologyshamsoftware as a medical device

Identifiers

PMID36060538
PMCPMC9436387
OpenAlexW4292478611

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.