The authors have read the journal's policy and have the following conflicts: Dr. Jonsson's co-authorship on one of the trials in the authors' review. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: EH FA MH SL UJ. Performed the experiments: EH FA SL UJ. Analyzed the data: EH FA UJ. Contributed reagents/materials/analysis tools: EH FA SL UJ. Wrote the paper: EH FA MH SL UJ.
Greater access to evidence-based psychological treatments is needed. This review aimed to evaluate whether internet-delivered psychological treatments for mood and anxiety disorders are efficacious, noninferior to established treatments, safe, and cost-effective for children, adolescents and adults.
We searched the literature for studies published until March 2013. Randomized controlled trials (RCTs) were considered for the assessment of short-term efficacy and safety and were pooled in meta-analyses. Other designs were also considered for long-term effect and cost-effectiveness. Comparisons against established treatments were evaluated for noninferiority. Two reviewers independently assessed the relevant studies for risk of bias. The quality of the evidence was graded using an international grading system.
A total of 52 relevant RCTs were identified whereof 12 were excluded due to high risk of bias. Five cost-effectiveness studies were identified and three were excluded due to high risk of bias. The included trials mainly evaluated internet-delivered cognitive behavioral therapy (I-CBT) against a waiting list in adult volunteers and 88% were conducted in Sweden or Australia. One trial involved children. For adults, the quality of evidence was graded as moderate for the short-term efficacy of I-CBT vs. waiting list for mild/moderate depression (
I-CBT is a viable treatment option for adults with depression and some anxiety disorders who request this treatment modality. Important questions remain before broad implementation can be supported. Future research would benefit from prioritizing adapting treatments to children/adolescents and using noninferiority designs with established forms of treatment.
A pressing challenge for mental health services is meeting the demand for the treatment of depression and anxiety disorders. Nearly 40% of the population is estimated to be in need of treatment at some time during their life for anxiety or depression
Only one third of depressed patients respond fully to pharmacotherapy
The internet has offered a new avenue for providing psychological treatments, but the effectiveness of these treatments is still an issue. Most reviews to date have found support for the use of internet-delivered cognitive-behavioral therapy (I-CBT)
First, the quality of the evidence needs to be carefully considered. In previous reviews, when used at all, quality assessments were restricted to a few indices of the internal validity of the individual studies. A proper assessment of risk of bias is essential to avoid the risk of drawing false conclusions, however, and it can be justified to exclude studies of higher risk of bias from the synthesis
Furthermore, investigators that conduct systematic reviews and meta-analyses are increasingly aware that not only individual studies but also the body of evidence needs to be systematically evaluated, because the confidence in the pooled effect estimates may be compromised not only by risk of bias in individual studies but also by several other factors (e.g., imprecision, inconsistency, indirectness, and publication bias)
Second, the issue of noninferiority has been largely ignored in previous reviews, but is necessary when comparing an existing evidence-based treatment (e.g., CBT) with a new one (e.g., I-CBT). In contrast to investigations of psychological therapy that involve new methods in areas where there is no known evidence-based treatment, the internet programs wisely employ known treatment techniques; only the manner of treatment delivery is altered. A greater reach and eventual cost savings could make internet therapies viable alternatives in healthcare. A critical issue, then, is whether they are noninferior to existing treatment. Noninferiority trials have gained increased attention to help in clinical decision making as the list of possible treatments grows, since a new treatment should be at least not inferior to existing evidence-based ones
Noninferiority trials are difficult to design and execute well
Third, the previous reviews have largely ignored potential adverse events (e.g., harms, side effects, and deterioration), which may prove important for implementation of remotely delivered psychological treatments. Finally, reviews to date have focused on CBT, while trials of other treatments have begun to emerge
The current review addresses all of the above issues. It has been conducted under the auspices of the Swedish Council on Health Technology Assessment (SBU), a government agency that has produced numerous systematic reviews evaluating the effects of various treatments (
Is internet-delivered psychological treatment efficacious, safe and cost-effective for mood and anxiety disorders in children, adolescents and adults?
Is internet-delivered treatment noninferior to established psychological treatments?
This systematic review was conducted at SBU. The inclusion criteria were pre-specified and a protocol was registered in advance internally at SBU (ref. no UTV2012/26), see
Only published studies in English were considered for this review. The criteria for eligibility included the following characteristics.
Children, adolescents and adults with anxiety or mood disorders according to the manuals of the American Psychiatric Association
Internet-delivered psychological treatments, defined as interventions based on an explicit psychological theory, not conducted at a clinic, and delivered to the patients via the internet. Any support had to be remotely delivered (e.g. email-like messages or telephone). The degree of support was categorized into pure self-help (no support), technician-assisted (e.g., non-clinical), or therapist-guided (i.e., clinical support).
Any established psychological treatments, waiting list, usual care, or attention control.
Change in symptoms of the primary disorder, adverse events, and cost per effect and per quality-adjusted life-years.
For short-term effects and risk of adverse events only RCTs were included. For long-term follow-up assessments (i.e., ≥6 months after post-assessment) RCTs and observational studies were included because of the ethical and practical dilemmas of conducting long-term RCTs. For cost-effectiveness data, economic evaluations based on individual-level data and decision models were eligible.
Electronic searches were conducted using Medical Subject Headings (MeSH) and relevant text word terms. The databases used were PubMed, Cochrane Library, CINAHL, PsycINFO, Psychology and Behavioral Sciences Collection (PBSC), TRIP database and CRD, up to March 4, 2013.
We used search terms for depression/mood and anxiety and for each disorder (e.g., panic, phobia), for a range of delivery methods (e.g., online, internet, web, computer, phone), and for therapy, psychotherapy, intervention, and terms for specific interventions (e.g., cognitive behavioral, psychodynamic, interpersonal). The detailed search strategies are found in
Two reviewers independently screened the titles and abstracts identified by the search strategy. All studies of potential relevance according to the inclusion criteria were obtained in full text and two reviewers independently assessed them for inclusion. Any disagreements were resolved by discussions. Reference lists were screened for additional studies of relevance.
From each included study of moderate or low risk of bias (see below), data was extracted and inserted in a table by one reviewer. A second reviewer audited the data extraction. Any disagreements were resolved by discussion.
Information was extracted from included trials on (1) participants (age, education, diagnosis, and method of diagnostic assessment); (2) treatment (including treatment paradigm, level of support, duration); (3) type of comparator (4) outcome measures of core symptoms; (5) adverse events or deterioration; (6) costs.
Two reviewers independently assessed the risk of bias with the use of checklists developed for each relevant study design
Trials that had a serious flaw were rated as high risk of bias; trials that met all or nearly all criteria were rated as low risk of bias, such as trials with a convincing comparator (e.g., an established treatment or a sham versions of attention bias modification) and no other obvious risk of bias; the remainder were rated as moderate risk of bias. Trials of moderate risk vary in their strengths and weaknesses: some trials likely provide valid results while others are only possibly valid. A high-risk trial is not valid; the results are at least as likely to reflect flaws in the study design as true differences among the trial arms. A fatal flaw may be reflected by one aspect introducing a high risk of bias or by failure to meet combinations of item criteria. The reviewers agreed on rules-of-thumb for decisions on categories and alert attention to trials that had, for example,
We included as noninferiority designs all comparisons of internet-delivered treatment vs. established psychological therapies (e.g. I-CBT compared with individual therapist-led CBT). For these comparisons we used a predefined noninferiority margin of
Potential publication bias was assessed for plausibly effective interventions by inspecting funnel plots and by a trim-and-fill procedure
The international grading system GRADE
High quality (⊕⊕⊕⊕) –We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality (⊕⊕⊕○) –We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality (⊕⊕○○)–Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low quality (⊕○○○) – We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of the effect.
In the GRADE system, evidence based on RCTs begins as high quality evidence, but may be rated down for several reasons, including study limitations, inconsistency of results, indirectness of evidence, imprecision or reporting bias. That is, for each type of treatment and support type, for each disorder and population, the quality of the evidence was assumed to be high at the outset, but subsequently rated down if there were limitations in the relevant studies. For example, there were three trials of CBT with clinical support vs. waiting list for adult participants diagnosed with panic disorder. Evidence of treatment efficacy start as being of high quality because the trials were RCTs, while study limitations (waiting list comparison [WLC]), inconsistency in the results (two trials show favorable effect, one shows no effect), and imprecision across studies (all three trials have small samples) entailed that the body of evidence finally received a low-quality rating. The quality of evidence was decided upon through discussions among the authors and input from an external group, the Quality and Priority Group at the agency. In line with agency guidelines we rated down for indirectness when only one RCT was included for a specific question, unless the included RCT was a multi-center trial.
We identified 52 relevant trials (54 reports), whereof 12 trials (13 reports) were excluded due to high risk of bias. The efficacy data thus included 39 reports with 40 RCTs of low or moderate risk of bias and 2 additional reports of long-term follow-ups of these trials that were included in the synthesis (
Diagnosis | Age, | Women | Employed | Married | Current | N | Intervention; support | Comparator |
Study, year, country | M yrs | /student |
/de facto relationship | medication |
||||
Berger, 2011, Switzerland |
40 | 70% | 75% | 24% | 25% | 76 | I-CBT; clinical | Waiting list |
I-CBT; none | ||||||||
Carlbring, 2013, Sweden |
44 | 83% | 81% | 55% | 14% | 80 | ACT, BA, mindfulness; clinical | Waiting list |
Choi, 2012, Australia |
39 | 80% | 66% | 56% | 18% | 63 | I-CBT; clinical | Waiting list |
Johansson, 2012a, Sweden |
45 | 71% | 74% | 49% | 31% | 121 | I-CBT, tailored; clinical | Online forum |
I-CBT, standardized; clinical | ||||||||
Johansson, 2012b, Sweden |
46 | 75% | 76% | 65% | 25% | 92 | I-PDT; clinical | Online supportive therapy |
Kessler, 2009, England |
297 | Therapist-led CBT via chat | TAU | |||||
Titov, 2010, Australia |
43 | 74% | 73% | 47% | 58% | 141 | I-CBT; clinical | Waiting list |
I-CBT; nonclinical | ||||||||
Vernmark, 2010, Sweden |
37 | 68% | 72% | 51% | 19% | 88 | I-CBT; clinical | Waiting list |
Therapist-led CBT via email | ||||||||
Andersson 2006, Sweden |
37 | 52% | 91% | 66% | 22% | 64 | I-CBT; clinical | Waiting list |
Andersson 2012, Sweden |
38 | 60% | 89% | 65% | 14% | 204 | I-CBT; clinical | Online forum |
Berger 2009, Switzerland |
29 | 56% | – | 42% | – | 52 | I-CBT; clinical | Waiting list |
Boettcher 2012, Germany/Switzerland |
38 | 37% | – | 65% | 6% | 68 | I-ABM | Sham therapy |
Carlbring 2007, Sweden |
33 | 65% | – | 58% | – | 60 | I-CBT; clinical | Waiting list |
Carlbring 2012, Sweden |
37 | 68% | – | 56% | 22% | 79 | I-ABM | Sham therapy |
Furmark 2009a, Sweden |
35 | 71% | 80% | 59% | 8% | 80 | I-CBT; clinical | Waiting list |
Furmark 2009b, Sweden |
34 | 66% | 88% | 52% | 14% | 58 | I-CBT; clinical | Bibliotherapy |
Hedman 2011, Sweden |
35 | 36% | 74% | – | 25% | 126 | I-CBT; clinical | Group CBT |
Neubauer 2013, Germany |
40 | 66% | – | – | 7% | 59 | I-ABM | Sham therapy |
Titov 2008a, Australia |
38 | 59% | 83% | 46% | 30% | 105 | I-CBT; clinical | Waiting list |
Titov 2008b, Australia |
37 | 63% | 90% | 54% | 26% | 88 | I-CBT; clinical | Waiting list |
Titov 2008c, Australia |
38 | 61% | 90% | 52% | 22% | 98 | I-CBT; clinical | Waiting list |
I-CBT; none | ||||||||
Bergström 2010, Sweden |
34 | 62% | 77% | – | 45% | 113 | I-CBT; clinical | Group CBT |
Carlbring 2005, Sweden |
35 | 71% | – | – | 51% | 49 | I-CBT; clinical | Individual CBT |
Carlbring 2006, Sweden |
37 | 60% | 75% | 67% | 54% | 60 | I-CBT; clinical | Waiting list |
Klein 2006, Australia |
(18–70) | 80% | – | – | 53% | 37 | I-CBT; clinical | Waiting list |
Wims 2010, Australia |
42 | 76% | 83% | 57% | 39% | 59 | I-CBT; clinical | Waiting list |
Andersson 2012, Sweden |
40 | 77% | 62% | 67% | 32% | 81 | I-PDT; clinical | Waiting list |
I-CBT; clinical | ||||||||
Paxling 2011, Sweden |
39 | 80% | – | – | 37% | 89 | I-CBT; clinical | Waiting list |
Robinson 2010, Australia |
47 | 68% | 76% | 64% | 32% | 150 | I-CBT; clinical | Waiting list |
I-CBT; nonclinical | ||||||||
Titov 2009, Australia |
44 | 76% | 40% | 67% | 29% | 48 | I-CBT; clinical | Waiting list |
Andersson 2012, Sweden |
34 | 66% | 93% | – | 23% | 101 | I-CBT; clinical | Online supportive therapy |
Spence 2011, Australia |
43 | 81% | 60% | 45% | 57% | 44 | I-CBT; clinical | Waiting list |
Andersson 2009, Sweden |
26 | 85% | – | – | – | 30 | I-CBT; clinical | Individual CBT |
Bell 2012, Australia |
35 | 67% | 69% | – | 60% | 83 | I-CBT; nonclinical | Waiting list |
Carlbring 2011, Sweden |
39 | 76% | 76% | 67% | 26% | 54 | I-CBT; clinical | Waiting list |
Johnston 2011, Australia |
42 | 59% | 84% | 50% | 29% | 139 | I-CBT; clinical | Waiting list |
I-CBT; nonclinical | ||||||||
Newby 2013, Australia |
44 | 78% | 66% | 63% | 40% | 109 | I-CBT; clinical | Waiting list |
Titov 2010, Australia |
40 | 68% | 82% | 53% | 47% | 86 | I-CBT; clinical | Waiting list |
Titov 2011, Australia |
44 | 73% | 63% | 46% | 54% | 77 | I-CBT; clinical | Waiting list |
March 2009, Australia |
9 | 55% | – | – | 0% | 72 | I-CBT; clinical | Waiting list |
ABM = Attention bias modification. CBT = Cognitive behavior therapy. GAD = Generalized anxiety disorder. OCD = Obsessive-compulsive disorder. PD = Panic disorder. PDT = Psychodynamic therapy. PTSD = Posttraumatic stress disorder.
Includes full- and part-time employed and students. For a few studies that only reported number of participants on sick leave, we report the proportion not on sick leave.
Psychotropic medication, although this was not stated explicitly in each report.
Includes major depressive episode acute/in partial remission, major depressive disorder, dysthymia; mainly mild/moderate severity, low suicidality.
Mainly GAD, social anxiety disorder, panic disorder; also major depressive disorder (
Nine trials were identified: eight had moderate risk of bias
None of the trials assessed noninferiority. Five evaluated the effect of I-CBT vs. a WLC
For the meta-analysis, the outcome chosen from each study was the Beck Depression Inventory I or II.
Disorder | Treatment | Support | Comparator | Outcome | Results | Quality of evidence (GRADE) | |
Unipolar depression | CBT | Clinical | Waiting list | BDI | CBT> waiting list | 323/5 | ⊕⊕⊕○ |
CBT | None | Waiting list | BDI | CBT> waiting list | 51/1 | ⊕○○○ |
|
PDT | Clinical | Online supportive therapy | BDI | n.s. | 92/1 | ⊕○○○ |
|
Chat CBT | – | Usual GP care | BDI | CBT> usual GP care | 297/1 | ⊕○○○ |
|
ACT | Clinical | Waiting list | BDI | n.s. | 80/1 | ⊕○○○ |
|
Social phobia | CBT | Clinical | Live group CBT | LSAS, SPS, SIAS | Noninferior | 126/1 | ⊕⊕○○ |
CBT | Clinical | Waiting list | SPS, SIAS | CBT> waiting list | 709/8 | ⊕⊕⊕○ |
|
CBT | Clinical | Bibliotherapy | LSAS, SPS, SIAS | n.s. | 58/1 | ⊕○○○ |
|
ABM | – | Sham therapy | LSAS, SPS, SIAS | n.s. | 206/3 | ⊕⊕⊕○ |
|
CBT | None | Waiting list | SPS, SIAS | n.s. | 66/1 | ⊕○○○ |
|
Panic disorder | CBT | Clinical | Waiting list | Varied among studies | CBT> waiting list | 151/3 | ⊕⊕○○ |
CBT | Clinical | Individual CBT | BSQ | n.s. | 49/1 | ⊕○○○ |
|
CBT | Clinical | Group CBT | PDSS | n.s. | 93/1 | ⊕○○○ |
|
GAD | CBT | Clinical | Waiting list | PSWQ | CBT> waiting list | 271/4 | ⊕⊕○○ |
CBT | Non-clinical | Waiting list | PSWQ | CBT> waiting list | 99/1 | ⊕○○○ |
|
PDT | Clinical | Waiting list | PSWQ | n.s. | 54/1 | ⊕○○○ |
|
Specific phobia | CBT | Clinical | Live CBT | BAT | n.s. | 30/1 | ⊕○○○ |
OCD | CBT | Clinical | Online supportive therapy | Y-BOCS | CBT> support | 101/1 | ⊕○○○ |
PTSD | CBT | Clinical | Waiting list | PCL-C | CBT> waiting list | 44/1 | ⊕○○○ |
Anxiety disorders | CBT | Clinical | Waiting list | Varied among studies | CBT> waiting list | 414/5 | ⊕⊕○○ |
Anxiety disorders | CBT | Non-clinical | Waiting list | WSAS, LSAS, PSWQ, GAI, FQ | n.s. | 83/1 | ⊕○○○ |
Anxiety disorders | CBT | Clinical | Waiting list | ADIS | CBT> waiting list | 72/1 | ⊕○○○ |
ABM = Attention bias modification. ADIS = Anxiety Disorders Interview Schedule. BAT = Behavioral approach test. BDI = Beck Depression Inventory (I or II). BSQ = Body Sensations Questionnaire. CBT = Cognitive behavior therapy. FQ = Fear Questionnaire. GAD = Generalized anxiety disorder. GAI = Generalized Anxiety Inventory. LSAS = Liebowitz Social Anxiety Scale. OCD = Obsessive-compulsive disorder. PCL-C = PTSD Checklist–Civilian version. PDSS = Panic Disorder Severity Scale, Self-Report. PDT = Psychodynamic therapy. PSWQ = Penn State Worry Questionnaire. SIAS = Social Interaction Anxiety Scale. PTSD = Posttraumatic stress disorder. SPS = Social Phobia Scale. Y-BOCS = Yale-Brown Obsessive-Compulsive Scale.
Study limitations (risk of bias);
Imprecision (e.g., small samples, heterogeneous effect sizes);
Indirectness (e.g., single trial).
Three other trials were included that evaluated one intervention each: one trial with an intervention that combined components from acceptance and commitment therapy, behavioral activation, and mindfulness
Sixteen trials were identified: three trials had low risk of bias
Eight trials with moderate risk of bias evaluated the effect of therapist-guided I-CBT compared to a WLC
For the meta-analysis, the outcome chosen from each study was the Social Interaction Anxiety Scale.
Two trials (three reports)
Three trials, two of low
For the meta-analysis, the outcome chosen from each study was the Social Interaction Anxiety Scale.
Nine trials of I-CBT were identified. Five trials had moderate risk
Three trials that compared therapist-guided I-CBT vs. a WLC with
Four trials with moderate risk of bias were identified
For the meta-analysis, the outcome chosen from each study was the Penn State Worry Questionnaire.
One trial found that I-CBT with non-clinical support by a technician was more effective than a WLC
We identified one trial of moderate risk of bias
Two relevant trials were identified; one trial with high risk of bias and one trial with moderate risk of bias that found that therapist-guided I-CBT was superior to WLC
We identified one trial of moderate risk of bias
Six trials of moderate risk of bias were identified that included participants with mixed anxiety disorders and/or MDD
Funnel plots and Duval and Tweedie's trim-and-fill procedure indicated no or trivial publication bias with respect to the pooled effect sizes for I-CBT for adults with depression, social phobia, and GAD.
We found four trials and excluded three due to high risk of bias because of various shortcomings. One trial of moderate risk of bias evaluated I-CBT for mixed anxiety disorders
Eight trials provided information on intervention-associated risks for depression
Of the 139 studies screened for cost-effectiveness data, five trials met the eligibility criteria. Two had a moderate risk of bias
In this review we assessed whether internet-delivered psychological treatments for mood and anxiety disorders are efficacious, noninferior to established treatments, associated with risk of adverse events, and cost-effective. We found limited to moderate evidence that for adults who seek out this treatment, therapist-guided I-CBT has a favorable short-term effect compared to waiting list for social phobia, panic disorder, generalized anxiety disorder, or mild to moderate major depression. We were not able to draw conclusions about noninferiority to proven treatments, long-term effects, adverse events, cost-effectiveness, or efficacy when given to children and adolescents.
Several reviews interpret the body of evidence such that I-CBT and established forms of CBT have comparable effects for mild to moderate depression and several anxiety disorders
There are a number of shortcomings with the existing trials that future studies would benefit from attending to. A common issue to these studies is that they were conducted by teams that developed the I-CBT program but had no role in developing the comparison face-to-face therapy. In addition, independent ratings of the quality of delivery of the therapy were not routinely included. Further, the face-to-face comparator was often group CBT and not individual CBT although the latter is generally the first-hand choice for anxiety and mood disorders
The diverging conclusions among extant reviews about equal efficacy between internet-delivered and face-to-face treatments highlight critical methodological aspects that set the present review apart from previous reviews
Third, we performed a comprehensive assessment of the risk of bias in the trials and excluded trials with high risk. Few trials for social phobia and depression were judged as having high risk of bias, which resulted in similar conclusions about short-term efficacy as the meta-analysis by Andrews et al.
We found only four relevant trials for children and adolescents, and three had high risk of bias. The three excluded trials concerned social anxiety, OCD, and diverse anxiety disorders (mainly GAD), respectively. Including them would not alter our conclusions. This turnout seems to reflect the slow progress in general among psychological interventions for children and adolescents
Finally, the trials included in this review may seem few in comparison to the expanding number of publications in the literature. However, we only included studies of participants with diagnosed mood and anxiety disorders. There are many other studies on internet-treatments in which participants have not been subjected to a diagnostic interview. Several of those trials used unguided interventions, which may explain why so few trials of unguided interventions were included. Also, we did not pool studies across treatments and support types, or across disorders, and therefore each cluster of studies yielded a modest number of trials despite an impressive amount overall.
Remote delivery is one of several promising avenues for expanding the reach of psychological interventions
Several trials assessed long-term outcomes of the treatments. Yet, no clear conclusions could be drawn about long-term effects as these data were limited mainly due to the observational design, attrition, and the lack of data on participants' receipt of other treatments during the follow-up period. Only eight efficacy trials reported on deterioration, and no trial suggested that adverse events in a broader sense had been monitored. There is clearly a need for better reporting of risk of safety data
Correlational evidence suggests that therapist guidance is beneficial for the outcome
We believe that using only trials with low or moderate risk of bias is an improvement to previous reviews. We are mindful of the fact that the ratings of risk of bias were subjective, which hampers the replicability of our findings. However, it is broadly recognized as poor review practice to disregard study quality altogether
I-CBT for adults with mild to moderate depression and select anxiety disorders may complement existing services. More research is needed before conclusions can be drawn about the efficacy of internet-delivered treatment regarding other anxiety disorders, other treatment methods than CBT, the treatment of children, long-term effects, safety, cost-effectiveness, and noninferiority to proven forms of treatment. We believe that a shift is warranted from waiting list trials to using active comparators, particularly direct comparisons with established treatments. Nonetheless, more research is needed to understand what makes psychological treatments effective, and for whom. This field unfolds rapidly, however, and it may not be long until remaining questions can be satisfactorily answered.
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The authors would like to thank Anders Norlund, at the Swedish Council on Health Technology Assessment, for valuable contributions to the review of cost-effectiveness analyses and Hanna Olofsson, also at the agency, for diligent assistance with the literature search.