Comprehensive Search Strategy for Immunotherapy Effectiveness Literature Review

This is an excellent goal! Designing a comprehensive search strategy is crucial for the rigor and reproducibility of any medical literature review, especially for PRISMA reporting. Immunotherapy is a broad and rapidly evolving field, so a detailed strategy is essential.

Let's break down the process step-by-step.

Comprehensive Search Strategy for Immunotherapy Effectiveness Literature Review

Research Question (Example - you will need to refine this for your specific review):
"What is the effectiveness of various immunotherapies in adult patients with solid tumors, compared to conventional treatments or placebo, in terms of overall survival, progression-free survival, and objective response rates?"

Self-correction: If your review is not limited to solid tumors, remove that qualifier. If it's not limited to adults, remove that. If you are interested in a specific cancer type (e.g., melanoma), replace "solid tumors" with "melanoma". This example provides a good starting point.

1. Identify Core Concepts & Keywords

Based on the example research question, the core concepts are:

• P (Population): Adult patients, Solid tumors (or specific cancer type)


• I (Intervention): Immunotherapy (broad), Specific immunotherapy types


• C (Comparison): Conventional treatments, Placebo (often implicit, or handled by study design)


• O (Outcome): Effectiveness, Overall Survival (OS), Progression-Free Survival (PFS), Objective Response Rate (ORR), Efficacy, Treatment outcome

2. Identify Relevant MeSH Terms (PubMed/Cochrane) & Emtree Terms (Embase)

This step is critical. MeSH (Medical Subject Headings) and Emtree are controlled vocabularies that allow for precise and comprehensive searching. Always explore the MeSH/Emtree trees to find broader and narrower terms.

Concept 1: Immunotherapy (Broad & Specifics)

• MeSH:


• "Immunotherapy"


• "Adoptive Immunotherapy" (covers CAR T-cell, TILs, etc.)


• "Checkpoint Inhibitors"


• "Chimeric Antigen Receptor T-Cells" (CAR T-cells)


• "Oncolytic Viruses"


• "Cancer Vaccines" (for therapeutic vaccines)


• "Cytokines" (e.g., Interleukins, Interferons - if relevant to your scope)


• "Immunoactive Agents"


• Emtree (Embase - often overlaps, but also more drug-specific):


• 'immunotherapy'/exp (explodes to narrower terms)


• 'checkpoint inhibitor'


• 'PD-1 inhibitor'


• 'PD-L1 inhibitor'


• 'CTLA-4 inhibitor'


• 'chimeric antigen receptor T cell'


• 'oncolytic virus'


• 'cancer vaccine'


• 'cytokine'


• 'immunomodulating agent'

• MeSH:


• "Treatment Outcome"


• "Survival Rate"


• "Disease-Free Survival"


• "Progression-Free Survival"


• "Response Rate" (often within "Treatment Outcome" but can be keyworded)


• "Clinical Benefit" (keyword)


• Emtree:


• 'treatment outcome'/exp


• 'survival'


• 'disease free survival'


• 'progression free survival'


• 'remission'


• 'drug efficacy'

• MeSH:


• "Neoplasms" (broad)


• "Solid Tumors" (no direct MeSH, use "Neoplasms" and keywords, or specific tumor MeSH)


• Specific MeSH for tumor types if applicable (e.g., "Melanoma", "Lung Neoplasms", "Breast Neoplasms", "Colorectal Neoplasms")


• Emtree:


• 'cancer'/exp


• 'tumor'/exp


• Specific Emtree terms (e.g., 'melanoma', 'lung cancer')

3. Build Boolean Search Strings (PubMed, Embase, Cochrane)

General Strategy for each database:
(Concept 1: Immunotherapy OR Specific Agents) AND (Concept 2: Effectiveness/Outcomes) AND (Concept 3: Population/Disease - optional, depending on breadth)

Important Notes:

• (truncation) captures variations (e.g., therap finds therapy, therapies, therapeutic).


• " (phrase searching) ensures words are searched together (e.g., "CAR T-cell").


• Always test individual terms and combinations.


• The [Mesh] tag in PubMed automatically explodes the term unless [MeSH:noexp] is used. Default for Emtree is also explosion with /exp.

3.1 PubMed Search String

(
  ("Immunotherapy"[Mesh] OR "Adoptive Immunotherapy"[Mesh] OR "Checkpoint Inhibitors"[Mesh] OR "Chimeric Antigen Receptor T-Cells"[Mesh] OR "Oncolytic Viruses"[Mesh] OR "Cancer Vaccines"[Mesh] OR "Cytokines"[Mesh])
  OR
  (immunotherap* OR "immune therap*" OR "immunologic agent*" OR "immunomodulat*" OR "immune check point inhibitor*" OR "PD-1 inhibitor*" OR "PDL1 inhibitor*" OR "CTLA-4 inhibitor*" OR "CAR T-cell*" OR "chimeric antigen receptor T cell*" OR "oncolytic virus*" OR "therapeutic vaccine*" OR "cytokine therap*" OR interleukin OR interferon OR nivolumab OR pembrolizumab OR atezolizumab OR durvalumab OR avelumab OR ipilimumab OR tremelimumab OR t-vec OR tisagenlecleucel OR axicabtagene OR brexucabtagene)
)
AND
(
  ("Treatment Outcome"[Mesh] OR "Survival Rate"[Mesh] OR "Disease-Free Survival"[Mesh] OR "Progression-Free Survival"[Mesh])
  OR
  (effectiv* OR efficac* OR outcome* OR survival OR response OR remission OR prognostic* OR "disease control" OR "clinical benefit" OR "treatment response" OR "overall survival" OR "progression-free survival" OR "objective response rate")
)
AND
(
  ("Neoplasms"[Mesh])
  OR
  (cancer OR neoplasm* OR carcinoma* OR tumor* OR malignanc* OR "solid tumor*")
)
AND humans[Filter] AND english[Filter]

• Combines broad MeSH terms with specific keywords and common drug names.


• Effectiveness concepts include MeSH and keywords.


• Disease concept is broad for "Neoplasms" and keywords.


• AND humans[Filter] AND english[Filter] are standard filters. You might also add ("clinical trial"[Publication Type] OR "randomized controlled trial"[Publication Type] OR "systematic review"[Publication Type] OR "meta-analysis"[Publication Type]) if you want to narrow by study design within PubMed.

3.2 Embase Search String (Ovid platform example - adapt for Embase.com)

(
  (immunotherapy/exp OR 'checkpoint inhibitor'/exp OR 'chimeric antigen receptor T cell'/exp OR 'oncolytic virus'/exp OR 'cancer vaccine'/exp OR cytokine/exp OR 'immunomodulating agent'/exp)
  OR
  (immunotherap* OR 'immune therap*' OR 'immunologic agent*' OR immunomodulat* OR 'immune check point inhibitor*' OR 'PD-1 inhibitor*' OR 'PDL1 inhibitor*' OR 'CTLA-4 inhibitor*' OR 'CAR T-cell*' OR 'chimeric antigen receptor T cell*' OR 'oncolytic virus*' OR 'therapeutic vaccine*' OR 'cytokine therap*' OR interleukin OR interferon OR nivolumab OR pembrolizumab OR atezolizumab OR durvalumab OR avelumab OR ipilimumab OR tremelimumab OR t-vec OR tisagenlecleucel OR axicabtagene OR brexucabtagene).ti,ab.
)
AND
(
  (treatment outcome/exp OR survival/exp OR 'disease free survival'/exp OR 'progression free survival'/exp OR 'drug efficacy'/exp)
  OR
  (effectiv* OR efficac* OR outcome* OR survival OR response OR remission OR prognostic* OR 'disease control' OR 'clinical benefit' OR 'treatment response' OR 'overall survival' OR 'progression-free survival' OR 'objective response rate').ti,ab.
)
AND
(
  (cancer/exp OR tumor/exp OR neoplasm/exp)
  OR
  (cancer OR neoplasm* OR carcinoma* OR tumor* OR malignanc* OR 'solid tumor*').ti,ab.
)
AND (human/de) AND (english/la)

• '/exp' is used for Emtree term explosion.


• .ti,ab. targets terms in title and abstract. You can use .mp. for "multi-purpose" (which includes title, abstract, original title, drug trade name, etc.).


• (human/de) and (english/la) are typical Ovid filters for human and English language.


• Embase is excellent for drug names and adverse events, so consider if your review needs to delve deeper into specific agents.

3.3 Cochrane Library Search String (CENTRAL - Cochrane Register of Controlled Trials)

Cochrane Central is primarily for identifying randomized controlled trials. It uses a simplified search interface compared to PubMed/Embase. You can often use MeSH terms directly or keywords.

Approach 1: Using their Advanced Search Builder

• Step 1 (Immunotherapy):


• MeSH terms: ("Immunotherapy" OR "Checkpoint Inhibitors" OR "Chimeric Antigen Receptor T-Cells" OR "Cancer Vaccines" OR "Oncolytic Viruses")


• Keywords (Title/Abstract): (immunotherap OR "immune therap" OR "CAR T" OR "PD-1" OR "PDL1" OR "CTLA-4" OR nivolumab OR pembrolizumab OR "oncolytic virus*")


• Combine these with OR.


• Step 2 (Effectiveness/Outcome):


• MeSH terms: ("Treatment Outcome" OR "Survival Rate" OR "Progression-Free Survival")


• Keywords (Title/Abstract): (effectiv OR efficac OR survival OR response OR "disease control")


• Combine these with OR.


• Step 3 (Disease - if specified):


• MeSH terms: ("Neoplasms")


• Keywords (Title/Abstract): (cancer OR neoplasm OR tumor)


• Combine these with OR.


• Step 4: Combine all three steps with AND.

(immunotherap* OR "immune therap*" OR "immunologic agent*" OR "immunomodulat*" OR "checkpoint inhibitor*" OR "PD-1" OR "PDL1" OR "CTLA-4" OR "CAR T-cell*" OR "chimeric antigen receptor*" OR "oncolytic virus*" OR "therapeutic vaccine*" OR "cytokine therap*" OR nivolumab OR pembrolizumab OR atezolizumab OR durvalumab OR avelumab OR ipilimumab OR tremelimumab OR t-vec OR tisagenlecleucel OR axicabtagene OR brexucabtagene OR MeSH descriptor: [Immunotherapy] OR MeSH descriptor: [Checkpoint Inhibitors] OR MeSH descriptor: [Chimeric Antigen Receptor T-Cells] OR MeSH descriptor: [Oncolytic Viruses] OR MeSH descriptor: [Cancer Vaccines] OR MeSH descriptor: [Cytokines])
AND
(effectiv* OR efficac* OR outcome* OR survival OR response OR remission OR prognostic* OR "disease control" OR "clinical benefit" OR "treatment response" OR "overall survival" OR "progression-free survival" OR "objective response rate" OR MeSH descriptor: [Treatment Outcome] OR MeSH descriptor: [Survival Rate] OR MeSH descriptor: [Disease-Free Survival] OR MeSH descriptor: [Progression-Free Survival])
AND
(cancer OR neoplasm* OR carcinoma* OR tumor* OR malignanc* OR "solid tumor*" OR MeSH descriptor: [Neoplasms])

4. Set Up Search Alerts

This is crucial for keeping your review current and capturing new publications during the review process.

• PubMed (My NCBI):


• Run your final, optimized search query.


• Click "Create Alert" or "Save Search" under the search bar.


• You'll be prompted to log in or create a My NCBI account.


• Configure alert settings: Name your search, choose email frequency (e.g., weekly, monthly), and format.


• Embase (Embase.com or Ovid):


• Run your final search query.


• Look for "Save Search / Alert" or similar options.


• For Ovid, click "Save History" then "AutoAlert".


• Configure frequency (weekly, monthly) and email settings.


• Cochrane Library (Wiley Platform):


• Run your final search query.


• Click "Save Search" or "Create Alert" (usually a bell icon or similar).


• Register for a free Wiley Online Library account if you don't have one.


• Set up the alert frequency (weekly, monthly).


• Google Scholar: While not as systematic, a broad alert here can sometimes catch things other databases miss.


• Go to Google Scholar.


• Run a simpler version of your search (e.g., "immunotherapy" "effectiveness" "cancer").


• Click the "Create alert" envelope icon in the left sidebar.


• Enter your email and create the alert.

5. Plan Gray Literature Search

Gray literature includes unpublished studies, conference abstracts, clinical trial registries, government reports, and dissertations. It's essential to reduce publication bias.

• Clinical Trial Registries:


• ClinicalTrials.gov: Search for ongoing or completed trials. Use broader terms (e.g., "immunotherapy" AND "cancer"). Look for terms like "completed," "active, not recruiting," "results available."


• EU Clinical Trials Register: (for trials in Europe)


• WHO International Clinical Trials Registry Platform (ICTRP): A portal to multiple national registries.


• Conference Proceedings/Abstracts:


• American Society of Clinical Oncology (ASCO): Access abstracts via their meeting library.


• European Society for Medical Oncology (ESMO): Meeting abstracts.


• American Association for Cancer Research (AACR): Meeting abstracts.


• Society for Immunotherapy of Cancer (SITC): Specific to immunotherapy.


• Search tip: Use the conference websites directly.


• Governmental/Organizational Reports:


• National Institutes of Health (NIH), National Cancer Institute (NCI): Websites for reports, guidelines, ongoing research.


• World Health Organization (WHO): Reports and guidelines.


• National Institute for Health and Care Excellence (NICE), Agency for Healthcare Research and Quality (AHRQ): For clinical guidelines and evidence reviews.


• Theses and Dissertations:


• ProQuest Dissertations & Theses Global: A large repository.


• Drug Company Websites: Major pharmaceutical companies involved in immunotherapy often publish trial data or summaries on their sites (e.g., Merck, BMS, Roche, Novartis). Search directly on their "clinical trials" or "research" sections.


• Preprint Servers (Use with caution):


• medRxiv, bioRxiv: Contains non-peer-reviewed manuscripts. Be transparent if you include these and acknowledge their pre-publication status. Generally, it's better to stick to peer-reviewed for effectiveness reviews unless your scope explicitly includes preliminary findings.

• Use simpler, broader search terms (e.g., "immunotherapy cancer effectiveness") as Boolean logic is often limited.


• Filter by date to focus on recent studies.


• Hand-search reference lists of included articles (particularly systematic reviews and guidelines) for additional relevant gray literature.


• Consider contacting experts in the field for unpublished data if appropriate for your review scope.

6. Document Search Strategy for PRISMA Reporting

Thorough documentation is paramount for PRISMA. Create a detailed log or table.

Components to Document:

• Database Names and Platforms: List all databases searched (e.g., PubMed via NCBI, Embase via Ovid, Cochrane Library via Wiley).


• Date of Search: State the full date (e.g., "All databases were searched on September 25, 2023"). If updated, list the update date.


• Full Search Strings: Provide the exact, complete Boolean search string for each database. This is critical for reproducibility.


• Self-correction: Do not just provide the concept breakdown; provide the actual query that was entered.


• Number of Results: Record the raw number of results retrieved from each database before deduplication.


• Limits/Filters Applied:


• Language (e.g., "English")


• Publication Type (e.g., "Clinical Trial," "Randomized Controlled Trial," "Systematic Review," "Meta-Analysis")


• Date Range (e.g., "from 2010 to present")


• Human studies (e.g., "human subjects")


• Any other specific filters (e.g., "adults")


• Search Alert Setup:


• Date alerts were set up.


• Databases for which alerts were created.


• Frequency of alerts (e.g., "weekly").


• Gray Literature Sources:


• List all gray literature sources searched (e.g., ClinicalTrials.gov, ASCO meeting abstracts).


• Dates searched.


• Search terms used (if different from main database strings).


• Number of relevant items identified (if quantifiable).


• Justification of Choices: Briefly explain why certain terms were chosen, why MeSH/Emtree were exploded, or why specific filters were used.


• Example: "MeSH terms were chosen and exploded to ensure comprehensive coverage of both broad and specific immunotherapy concepts and related outcomes."


• Librarian Consultation: State if a medical librarian was consulted for strategy development and optimization. This enhances credibility.

Final Recommendations:

• Pilot Testing: Run your search strings in each database. Review the first 50-100 results to see if they are relevant. Adjust terms if necessary (e.g., if too many irrelevant results, add more specific terms or use NOT for exclusions; if too few, broaden terms or explode more MeSH).


• Librarian Consultation: Seriously consider collaborating with a medical librarian. They are experts in search strategy design and database specificities.


• Iterative Process: Search strategy development is iterative. Start broad, refine, test, and then optimize.


• Transparency: Be completely transparent in your documentation, making it easy for others to replicate your search.