The Role of Digital Biomarkers in Clinical Trials 

Digital biomarkers provide several advantages over traditional clinical outcome assessments (COAs). They offer continuous monitoring, real-time data collection, and improved participant engagement. These features are particularly valuable in clinical trials, where accurate and timely data collection is crucial for assessing the efficacy and safety of investigational treatments. 

One of the primary benefits of digital biomarkers is their potential to offer more objective evidence and improve signal detection. Trials in many areas of neuroscience, including psychiatry often suffer from high placebo response rates and low drug-placebo separation due to factors such as misdiagnosis, enrollment pressures, and subjective assessments. Digital biomarkers may prove to be vital tools to addressing these longstanding issues. 

Types of Digital Biomarkers 

Several types of digital biomarkers have been identified as valuable in clinical trials. These include vocal biomarkers, facial expression analysis, movement biomarkers, and physiological measures. 

• Vocal Biomarkers: Vocal biomarkers analyze speech patterns, including speech latency, tone, and other vocal features. These biomarkers have shown promise in psychiatric and neurological clinical trials ¹. For example, speech latency variables have been used to enrich participant selection in depression studies, enhancing the primary outcome effect size². Vocal biomarkers can also identify data quality issues and duplicate subjects, improving the overall quality of the trial data. 
• Facial Expression Analysis: Facial expressions can reveal significant insights into psychiatric and neurological conditions. AI-powered facial expression analysis can extract, analyze, and interpret complex behavioral and physiological signals, providing a rich source of objective, quantifiable data ³. This technology is particularly useful in early detection and proactive intervention for conditions such as schizophrenia, dementia, and anxiety disorders. 
• Movement Biomarkers: Movement biomarkers assess motor function and human behavior through wearable devices. These biomarkers are valuable in trials for conditions such as Parkinson’s disease and other neurological disorders. They provide continuous monitoring and real-time data, allowing for a more comprehensive assessment of treatment efficacy. 
• Physiological Measures: Physiological biomarkers include heart rate, blood pressure, and other vital signs measured through wearable devices. These biomarkers offer continuous monitoring and can provide early indicators of treatment efficacy and safety. They are particularly useful in trials for cardiovascular and metabolic disorders. 

Case Examples 

• Depression and Schizophrenia Trials: In a recent depression study, the incorporation of speech latency variables enabled an enrichment strategy for participant selection. The results were startling, enhancing the primary outcome effect size by 52%². This indicates that speech latency is an objective marker of depression, schizophrenia, and other psychiatric conditions that can feasibly be used for enrichment. Additionally, a follow-up study demonstrated similar results using a modification of the same speech latency measure, showing dramatic improvements in signal detection for schizophrenia⁴. Taken together, these findings support our understanding of speech latency as an objective marker in psychiatric conditions. 
• Parkinson’s Disease Trials: Movement biomarkers have been extensively used in Parkinson’s disease trials. Wearable devices that monitor motor function provide continuous data on tremors, gait, and other motor symptoms. This real-time data collection allows for a more accurate assessment of treatment efficacy and can identify subtle changes in motor function that may not be captured through traditional assessments. 
• Cardiovascular Trials: Physiological biomarkers such as heart rate and blood pressure are critical in cardiovascular trials. Wearable devices that continuously monitor these vital signs provide early indicators of treatment efficacy and safety. This continuous monitoring can detect adverse events earlier, allowing for timely intervention and improving patient safety. 

Challenges and Considerations 

While digital biomarkers offer significant advantages, there are also challenges and considerations to address. One of the primary challenges is the validation and standardization of digital biomarkers. Ensuring that these biomarkers are reliable, reproducible, and clinically meaningful is crucial for their successful integration into clinical trials. 

Another consideration is the potential for data overload. Digital biomarkers generate vast amounts of data, which can be overwhelming to analyze and interpret. Advanced data analytics and machine learning algorithms are essential for extracting meaningful insights from this data. 

Additionally, there are ethical and privacy concerns related to the use of digital biomarkers. Ensuring that patient data is securely collected, stored, and used is paramount. Clear guidelines and regulations are needed to address these concerns and protect patient privacy. 

Future Directions 

The future of digital biomarkers in clinical trials looks promising. Advances in artificial intelligence and machine learning will continue to enhance the accuracy and reliability of digital biomarkers. New, low-burden approaches to the assessment of clinically relevant features of speech, motor function, and human behavior are expected to emerge. 

Moreover, the integration of digital biomarkers with other digital health technologies, such as telemedicine and remote monitoring, will further improve patient engagement and trial efficiency. The use of digital biomarkers in decentralized and hybrid clinical trials is also expected to increase, providing more flexibility and convenience for participants. 

Conclusion 

Digital biomarkers offer substantial value in clinical trials by providing objective, continuous, and real-time data. They enhance the accuracy and efficiency of trials, reduce placebo response, and improve patient engagement. Vocal biomarkers, facial expression analysis, movement biomarkers, and physiological measures are among the most promising digital biomarkers in clinical trials. While there are challenges to address, the future of digital biomarkers in clinical trials looks bright, with continued advancements in technology and data analytics paving the way for more effective and efficient clinical research. 

References 

1. Cohen, A., Rodriguez, Z., Opler, M., Kirkpatrick, B., Milanovic, S., Piacentino, D., Szabo, S. T., Tomioka, S., Ogirala, A., Koblan, K. S., Siegel, J. S., Hopkins, S. Evaluating speech latencies during structured psychiatric interviews as an automated objective measure of psychomotor slowing. Psychiatry Res. 2024 Oct; 340:116104.

2. Siegel, J., Cohen, A., Szabo, S., Tomioka, S., Opler. M., Kirkpatrick, B., Hopkins, S. (2024). Enrichment using speech latencies improves treatment effect size in a clinical trial of bipolar depression. Journal of Psychiatry Research, 340, 5. https://www.sciencedirect.com/science/article/abs/pii/S0165178124003901   

3. Cowan, T., Rodriguez, Z. B., Strauss, G. P., Raugh, I. M., Cohen, A.S. Eur Arch Psychiatry Clin Neurosci. 2024 Oct;274(7):1771-1775.

4. Cohen, A., Kirkpatrick, B., Opler, M., Sedway, J., Tatsumi, K., Bhat, S., Bhat, L. Enrichment based on speech latency enhances treatment effects in a phase III study of brilaroxazine. Poster., 2024 Nov. 

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What is the accelerated approval pathway? What are the pros and cons of the accelerated approval pathway? What changes are being implemented as a result of the latest draft guidance on expedited programs for serious conditions published in December 2024?

Response:

What is the Accelerated Approval Pathway?

The accelerated approval pathway is a cornerstone of the Food and Drug Administration’s (FDA) efforts to address unmet medical needs and enable faster access to life-saving treatments. The accelerated approval pathway authorizes the use of investigational treatments based on preliminary evidence, such as surrogate endpoints that predict clinical benefits. This pathway is reserved for serious or life-threatening conditions with no adequate existing therapies. This pathway should not be used if it is infeasible to complete an adequate and well-controlled clinical trial to verify and describe clinical benefits, since confirmatory clinical studies will be required to be completed after approval.^{1, 2}

The FDA’s accelerated approval pathway was developed during the HIV epidemic of the 1980s as a mechanism to expedite the availability of treatments for serious and life-threatening conditions. Today, it has become an integral part of oncology drug approvals, with 80 percent of accelerated approvals granted for cancer therapies.³

FDA regulation 21 CFR Part 312 Subpart E outlines the expedited procedures to facilitate the development and marketing of these drugs.⁴ Patients and healthcare providers are often more willing to accept higher risks for treatments addressing life-threatening illnesses due to the lack of alternatives.

Benefits of the Accelerated Approval Pathway

There are many benefits to the accelerated approval pathway process, including:

1. Rapid Access to Treatments: By allowing earlier approval, patients with life-threatening conditions gain access to innovative therapies sooner.
2. Incentivizing Innovation: The pathway encourages pharmaceutical companies to invest in treatments for rare and difficult-to-treat conditions.
3. Addressing Unmet Needs: It prioritizes conditions with limited or no available therapies, meeting critical medical demands.

Challenges and Controversies

While the accelerated approval pathway is invaluable, it is not without challenges. Some of the key issues include:

1. Reliance on Surrogate Endpoints: Accelerated approval pathways are based on a product demonstrating an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality.^{1, 2} Drugs are often approved based on measures that may not translate into real-world clinical benefits, especially in oncology. For example, only 37 percent of drug-indication pairs approved between 2013 and 2023 converted to regular approval after confirmatory trials.³

2. Delayed Confirmatory Trials: Many drugs face prolonged delays before confirmatory trials are completed. Between 2013 and 2017, the average duration from approval to trial completion increased from 3.4 to 4.5 years.^{3, 6} One cause of delays may be due to the confirmatory studies not being underway at the time of accelerated approval, which may lead to a lag.⁷

3. Drug Withdrawal Issues: Over the last decade, 23 percent of accelerated approvals in oncology were withdrawn due to lack of benefit over standard of care.⁵ Withdrawing ineffective drugs can be slow and contentious. For instance, Makena, approved in 2011, was not withdrawn until 2023 despite failing confirmatory trials analyzed in 2019. This leads to concerns that patients are being treated during this withdrawal period with drugs that might not be of sufficient benefit and with possible increased toxicity.^{6, 8, 9}

4. High Costs: Accelerated approval drugs often carry significant costs, even without robust evidence of their benefits.⁶

5. Inconsistent Guidance: Withdrawn drugs are sometimes still recommended in national treatment guidelines, contributing to confusion. Over one-third of accelerated approval indications that had been withdrawn since approval by the FDA continue to be recommended in national guidelines,¹⁰ indicating a need for improved transparency and disclosure to patients regarding which treatments were approved via the accelerated pathway without having demonstrated positive confirmatory results at time of recommended treatment. The FDA Oncology Center of Excellence created the initiative “Project Confirm” to promote transparency of outcomes related to accelerated approval for oncology indications.¹¹

Recent Updates and Reforms

The FDA’s December 2024 draft guidance introduces new conditions to address existing challenges in the accelerated approval pathway. These include:

1. Requiring sponsors to initiate post-approval studies prior to or within a specified timeframe after accelerated approval.
2. Including clear limitations of the drug’s usefulness and any uncertainty of anticipated clinical benefits in the labeling under the INDICATIONS AND USAGE section with reference to the CLINICAL STUDIES section for a discussion of available evidence.
3. Requiring sponsors to submit reports on post-approval study progress approximately every 180 days.
4. Requiring that all copies of promotional materials be submitted to the FDA by the sponsor for review within specific time frames.
   • Promotional materials intended to be disseminated or published within 120 days following marketing approval need to be submitted during the preapproval review period.
   • After 120 days following marketing approval, promotional materials need to be submitted at least 30 days prior to the intended publication or dissemination of the materials.
5. The FDA will publish information provided in the sponsor progress reporting of confirmatory trials.¹

Conclusion

The accelerated approval pathway has played a vital role in addressing urgent medical needs. However, it requires continuous refinement to balance expedited access with robust evidence of safety and efficacy. Recent reforms and ongoing oversight aim to strengthen this balance, ensuring the pathway fulfills its mission to deliver life-saving innovations while protecting patient safety.

If you have any additional questions about the accelerated approval pathway guidance or other ethical review questions, please complete the form below. WCG’s nearly 200 Institutional Review Board (IRB) experts are ready to support your study and to address your specific inquiries.

References

1. Draft FDA guidance for Industry: Expedited Program for Serious Conditions – Accelerated Approval of Drugs and Biologics. December 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/accelerated-approval-expedited-program-serious-conditions.
2. FDA Accelerated Approval Program website. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program.
3. Ian T. T. Liu, MD, JD, MPH, MS; Aaron S. Kesselheim, MD, JD, MPH; Edward R. Scheffer Cliff, MBBS, MPH. Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval. JAMA. 2024; 331(;7) 1471-1479.
4. Regulation 21CFR https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=312&showFR=1&subpartNode=21:5.0.1.1.3.5.  
5. Parikh et al. Exposure to US Cancer Drugs with Lack of Confirmed Benefit After US Food and Drug Administration Accelerated Approval. JAMA Oncology. 2023 Volume 9 (5); 567-569.
6. Gyawali et al. The Accelerated Approval Program for Cancer Drugs – Finding the Right Balance. NEJM. 2023; Volume 389(11); 968-970.
7. Jazowski et al. Time to Confirmatory Study Initiation After Accelerated Approval of Cancer and Noncancer Drugs in the US. JAMA International Medicine. 2023; Volume 183(7); 737-739.
8. NPR article. FDA pulls the only approved drug for preventing premature birth off the market. April 5, 2023. https://www.npr.org/sections/health-shots/2023/04/06/1167919912/fda-pulls-the-only-approved-drug-for-preventing-premature-birth-off-the-market.
9. Aaron et al. The FDA Struggle to Withdraw Makena: Problems with the Accelerated Approval Process. JAMA. 2022; 328(24); 2394-2395.
10. Cliff et al. National Comprehensive Cancer Network Guideline Recommendations of Cancer Drugs with Accelerated Approval. JAMA Network Open. 2023. Volume 5(11);https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2811820?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jamanetworkopen.2023.43285#google_vignette.
11. https://www.fda.gov/about-fda/oncology-center-excellence/project-confirm.

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In January 2025, the Food and Drug Administration (FDA) and The Office for Human Research Protections (OHRP) issued a draft guidance on recommendations to industry, investigators, institutions, and Institutional Review Boards (IRBs) when tissue biopsies are included in clinical trials to evaluate investigational medical products. The draft guidance defines a biopsy as a procedure that involves the collection of tissue from a study participant as part of a clinical trial protocol. The draft guidance reflects a potential change in approach on how the assessment of risk and benefit for a child might be evaluated in a trial that includes a research biopsy.

Biopsies for Research Purposes

Biopsies are often needed to ensure that a participant has a particular condition or biomarker that is targeted by the drug or biologic product before enrollment in a trial, to obtain other data related to eligibility, or to evaluate a primary or secondary endpoint. Of note, any time a biopsy is considered for inclusion in a clinical trial, the risks of obtaining the biopsy must be weighed against the anticipated benefits and the importance of any knowledge gained from collection of the biopsy. When a biopsy is included in a clinical trial, the rationale and scientific justification should be clearly outlined in the protocol. If a biopsy for a particular participant includes an unacceptable level of risk, that participant should not be included in the trial. If biopsies are included in protocols as non-key secondary or exploratory endpoints, are not needed for determining eligibility, or are solely collected for future use, the FDA and OHRP state that these biopsies should be optional (protocol specified but not necessary to participate) since these biopsies may unnecessarily increase risks and burdens to participants and may discourage participation in the trial. 

Informed consent should be obtained before any research related biopsies are collected. It should outline if the biopsy is required or optional, describe the risks and benefits associated with the collection of the biopsy, and be conducted in an environment where there is no possibility of coercion or undue influence. Participants should have the right to withdraw their consent to provide a biopsy at any point during the trial, noting that if a biopsy is required, not collecting the biopsy may impact the participant’s ability to continue in the trial. Withdrawal of consent for optional biopsies would not have an impact on continued trial enrollment.

Certain types of biopsies may involve more risk. For example, a brain biopsy involves significantly more risk than a skin biopsy. In situations where the biopsy involves considerable risk, a strong scientific rationale for the biopsy should be provided and alternative approaches, such as collecting information from existing pathology, rather than obtaining a new biopsy, should be considered whenever possible.

A biopsy could be required in adults in the following situations:

• To identify participants with a particular finding that may make them more likely to respond to a particular treatment, like human epidermal growth factor 2 (HER2) positive disease for HER2-targeted therapies.
• To identify participants who may be more likely to have side effects or toxicities from use of the investigational treatment, (e.g., increased toxicities for patients with Kirsten rat sarcoma viral oncogene homolog [KRAS] and/or neuroblastoma Ras viral oncogene homolog [NRAS] mutated colon cancer treated with certain epidermal growth factor receptor antagonists).
• To identify participants who would not be likely to benefit from the treatment (e.g., a patient with significant renal scar tissue may have no signs of inflammation and therefore may not respond to immunosuppression).
• To evaluate primary and key secondary trial endpoints.
• To evaluate treatment response.
• Obtain tissue to produce a gold standard (truth standard) by a known high-validity diagnostic method to test an investigational diagnostic product. For example, to verify that an imaging agent is effective in recognizing a tumor compared to histology.^1,2

Biopsies for Pediatric Participants

A biopsy done in children as part of a clinical trial must comply with special considerations under 21 CFR 50, subpart D and 45 CFR 46, subpart D.³ A biopsy (and any biopsy associated procedures, such as procedural sedation) that is performed solely for research purposes and not needed for clinical management or routine clinical care should be evaluated to determine whether it offers prospect of direct benefit to the enrolled child.

One nuance outlined in this draft guidance is that if a biopsy is performed to establish whether a child is likely to benefit from treatment with the investigational agent, performing the biopsy as part of the clinical trial could also be considered a benefit. For example, if a drug or biologic targets a particular biomarker or condition, the biopsy may be needed to establish whether the child has the biomarker or condition and is more likely to respond to the therapy and thus benefit from the treatment. Otherwise, in situations where there is no benefit and a biopsy is performed for research purposes, such as to evaluate a primary or key secondary endpoint, the risk must be limited to “minimal risk” or a “minor increase over minimal risk.” Biopsies that exceed minimal risk but are considered to meet criteria as a minor increase over minimal risk must also contribute to generalizable knowledge about the child’s disorder or condition. Large organ biopsies are generally considered to exceed the minor increase over minimal risk threshold and should not be done in a clinical trial unless needed for clinical purposes or offer a prospect of direct benefit as described above.

In pediatric trials, particularly those in oncology where treatments may be focused on a specific molecular marker,⁴ establishing whether the child is likely to benefit from the treatment is important. Unnecessarily exposing a child to a treatment without establishing a tumor type or tumor biomarker targeted by the investigational agent would expose the child to unnecessary risk without any anticipated benefit. In the past, these biopsies may have been considered by IRBs to not offer a benefit, thus limiting enrollment to children who either had previously had a biopsy done for clinical purposes or who had stored tissue for analysis. This approach may have inadvertently excluded children who would have benefited if the biopsy could have been done as part of the trial.

Conclusion

The draft guidance provided by the FDA and OHRP underscores the critical considerations necessary when including tissue biopsies in clinical trials. It highlights the importance of weighing the risks and benefits, obtaining informed consent, and ensuring that the scientific rationale is robust and justified. Biopsies should be optional if not essential for determining eligibility or other primary trial endpoints. For children, a biopsy and any biopsy associated procedures performed solely for research purposes and not needed for clinical management or routine clinical care should be evaluated to determine whether performing the biopsy offers a prospect of direct benefit to the enrolled child. A biopsy performed as part of a research study could be considered to offer a benefit to the child if the biopsy is performed to establish whether a child is likely to benefit from treatment with the investigational agent, such as to identify a specific molecular target or condition.

If you have additional questions regarding biopsies in adult or pediatric studies or other IRB-related inquiries, please don’t hesitate to contact us by completing the form below. WCG’s IRB experts are here to assist you with any ethical or regulatory questions. Reach out today.

References:

1. Guidance for Industry Developing Medical Imaging Drug and Biological Products Part 2: Clinical Indications, accessed January 7, 2025, https://www.fda.gov/media/71226/download.
2. Guidance for Industry Developing Medical Imaging Drug and Biological Products, Part 3: Design, Analysis, and Interpretation of Clinical Studies, accessed January 7, 2025, https://www.fda.gov/media/71237/download.
3. Ethical Considerations for Clinical Investigations of Medical Products Involving Children Guidance for Industry, Sponsors, and IRBs, accessed January 7, 2025, https://www.fda.gov/media/161740/download.
4. How to Navigate Researching Targeted Therapies in Pediatric Oncology Clinical Trials, Fierce Biotech, accessed January 7, 2025, How to Navigate Researching Targeted Therapies in Pediatric Oncology Clinical Trials | Fierce Biotech.

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Alzheimer’s Disease (AD) is a relentless neurodegenerative disorder that affects millions globally. Early detection and intervention are key to managing the disease and enhancing patients’ quality of life. In the quest for effective treatments, clinical trials often rely on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) as a primary endpoint. This semi-structured interview is also a crucial inclusion criterion in most trials. However, these trials typically require large participant samples and extended follow-up periods to observe significant placebo decline and detect treatment effects. 

To streamline these trials, identifying clinical factors that predict placebo decline is essential. These factors can help enrich trial samples or serve as stratification variables for earlier phase trials with smaller samples. In this study, we examined the utility of common screening measures used in early symptomatic AD trials to determine their predictive value for progression on the CDR-SB. 

Study Overview 

We analyzed data from 3,606 participants across six early symptomatic AD studies. These studies included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) delayed Memory Index (DMI) cutoff of 85 or less, and the Mini Mental Status Examination (MMSE) cutoff of 20+ for inclusion. Using forward and backward stepwise regressions, we identified the best model for predicting change in CDR-SB from screening to month 18. The predictor variables included RBANS total scale index score, RBANS DMI, MMSE total, CDR-SB, and age. The final model was evaluated using linear regression to determine the magnitude and direction of the predictor variables. 

Key Findings 

The final model, identified by both forward and backward stepwise regressions, included all variables except RBANS DMI. The linear regression analysis revealed that the model was statistically significant (adjusted R2 = 0.1216; p-value < 0.0001). Subject age was positively associated with change in CDR-SB (coefficient = 0.007), while RBANS total scale index score (coefficient = -0.057), MMSE total (coefficient = -0.121), and screening CDR-SB (coefficient = -0.087) were negatively associated. 

Implications for Clinical Trials 

Our findings indicate that screening measures such as RBANS, MMSE, and CDR are valuable tools in predicting disease progression in early symptomatic AD. The RBANS total scale index score showed the strongest relationship to progression on CDR-SB. Participants in the lowest quartile on this measure progressed more than 2.5 times the rate of those in the highest quartile. These insights can be instrumental in designing future clinical trials, either by enriching study samples for faster progression or for stratification purposes. 

Conclusion 

The study underscores the importance of using clinical screening data, including RBANS total scale index score, MMSE total, CDR-SB, and age, in predicting disease progression in early symptomatic AD. By leveraging these measures, researchers can enhance the efficiency and effectiveness of clinical trials, ultimately paving the way for better treatment options for Alzheimer’s Disease. 

References: 

1. Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology 1993; 43: 2412-4. 

2. Randolph, C. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). NCS Pearson, 1998, 2012. 

3. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res 12(3):189–198. 

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Parkinson’s Disease (PD) is a progressive neurological disorder affecting millions worldwide. Clinical trials are essential for developing new treatments and improving the quality of life for those with PD. The Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III is a widely used tool to measure changes in motor function over time in these trials. Despite its reliability, motor assessments by experienced raters can still be prone to subjective interpretation and scoring errors. 

To address this issue, Independent Review (IRev) is often used in clinical trials to independently verify primary endpoint data. This project evaluated IRev data collected in PD trials using the MDS-UPDRS part III, with the following objectives: 

1. Evaluate the frequency of MDS-UPDRS part III scoring discrepancies identified by independent reviewers in PD clinical trials. 

2. Identify items most prone to discrepancies during IRev. 

3. Assess whether the frequency of discrepant scores varies by disease severity measured by the MDS-UPDRS part III total score. 

Methods 

Aggregated MDS-UPDRS part III data from three multi-national double-blind clinical trials of PD were analyzed. The data included 20,239 assessments independently reviewed via video recording by a team of trained and calibrated clinicians (ICC 0.86). Assessments were divided into quartiles based on the severity of motor symptoms, and discrepancy rates were calculated for each severity group. 

Results 

Approximately 25% of assessments reviewed had at least one scoring discrepancy following IRev. Discrepancies were highest for Hoehn and Yahr (H&Y), finger tapping, and hand movements, and lowest for rest tremor amplitude items, freezing of gait, and speech. Assessments with lower part III total scores had the highest rate of discrepancies. Differences among severity quartiles were statistically significant, with discrepancy rates decreasing as motor symptom scores increased (F= 18.57; df = 3, 20159; p<.001). 

Implications for Clinical Trials 

Despite robust training, the high frequency of scoring discrepancies, particularly for subjects in earlier disease stage, underscores the need for continued efforts to improve the accuracy and reliability of motor assessments in PD clinical trials. This could involve additional training for raters, application of data surveillance methodologies, or even development of more objective assessment tools. Particular attention should be paid to assessments of subjects with milder motor symptoms, as these individuals are more likely to be rated inaccurately. 

Conclusion 

This study provides valuable insights into the frequency and nature of scoring discrepancies in MDS-UPDRS part III assessments in PD clinical trials. By addressing these issues, researchers can enhance the quality of data collected in PD trials, paving the way for more effective treatments and better outcomes for individuals living with Parkinson’s Disease.

References: 

1. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340. PMID: 19025984. 

2. Richards M, Marder K, Cote L, Mayeux R. Interrater reliability of the Unified Parkinson’s Disease Rating Scale motor examination. Mov Disord. 1994 Jan;9(1):89-91. doi: 10.1002/mds.870090114. 

3. Siderowf A, McDermott M, Kieburtz K, Blindauer K, Plumb S, Shoulson I; Parkinson Study Group. Test-retest reliability of the unified Parkinson’s disease rating scale in patients with early Parkinson’s disease: results from a multicenter clinical trial. Mov Disord. 2002 Jul;17(4):758-63. doi: 10.1002/mds.10011. 

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Overview of AI in Clinical Trials 

Although AI technology is not new, its adoption has surged remarkably in recent years, particularly with generative AI. AI encompasses various technologies, including machine learning, natural language processing, and robotics. Generative AI, a subset of AI, works with large language sets and can autocomplete tasks based on context. This technology is now being used to enhance the quality of clinical trials, reduce cycle times, and lower costs.  

Applications of AI in Drug Development 

AI enables deep learning models in target identification, validation, compound screening, and lead generation within drug development, streamlining the entire drug development pipeline. These models predict molecule stability, toxicity, and potential side effects, ultimately identifying more successful candidates for development. AI also plays a significant role in personalized medicine, analyzing population subsets to make treatments more effective. Additionally, AI aids in drug repurposing by analyzing real-world data to improve future drug development. 

AI’s Role in Clinical Trials 

Within clinical trials, AI contributes significantly across various stages of protocol design, study start-up, and recruitment. AI contributes to clinical trials by optimizing study design, predicting trial outcomes, and reducing participant and site burden. AI models help select the best sites for studies, predict patient dropouts, and identify participant populations more likely to respond to treatments. Using large data sets, such as Electronic Health Records (EHRs) and imaging data, AI simplifies patient trial matching and creates trial awareness. AI also assists in generating clinical trial reports more efficiently. 

Challenges and Opportunities of AI in Clinical Trials 

Implementing AI in clinical trials requires significant investment, training, and validation. Trust in AI remains critical, especially with complex machine learning models. Infrastructure modernization and data integration are essential to overcome barriers and improve efficiency. Despite these challenges, AI offers immense potential in improving participant outcomes and reducing costs. 

AI helps manage the exponential growth of data in clinical trials, ensuring efficient data processing, categorization, and quality checks. This enhanced data management can improve the speed and accuracy of trial outcomes. 

Advancements in AI Imaging 

AI’s ability to detect changes in images that escape the human eye can lead to earlier diagnosis and better disease progression modeling. This technology has immense potential in oncology, helping to predict tumor progression and improve patient outcomes. In one case, an AI-driven imaging tool offered precise tumor progression modeling. 

The Future Outlook for AI in Clinical Trials  

AI holds immense promise for clinical trials by improving quality, reducing timelines, and cutting costs. However, continued advancements in data quality, transparency, and trust-building are essential to harness AI’s full potential. Integrating AI in clinical trials should augment existing processes, ensuring robust oversight and human intervention where necessary to ultimately continue driving innovation in clinical research. 
 

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By leveraging WCG’s vast experience and tools, institutions can enhance participant enrollment, improve data quality, and accelerate study start-up timelines, ultimately driving research to results faster and more effectively. 

“Our goal is to empower research teams to do more in spite of financial constraints, ensuring that important clinical research can thrive even in the face of budget challenges,” said Sam Srivastava, chief executive officer, WCG. “As institutions grapple with reduced funding, we can support them with solutions needed to advance their trials. While doing so, we’ll lead conversations aimed at solving some of our greatest challenges and advancing solutions to drive resiliency in scientific discovery without compromising quality or efficiency.” 

WCG’s Research Resilience Solutions enable institutions to:  

• Increase Trial Volume: Institutions can undertake a greater number of industry-sponsored trials without adding substantial administrative burdens with the support of WCG solutions, thereby maximizing institutional research capabilities.  

• Accelerate Study Start-Up: By improving study start-up timelines with a target of 90 days, institutions can reduce delays and begin trials faster, enhancing overall research productivity.  

• Enhance Enrollment and Data Integrity: Flexible staff augmentation solutions help institutions meet the complexity of participant enrollment in today’s clinical trials while ensuring the integrity and quality of their data, thereby bolstering the impact of their research.  

• Enhance Participant and Public Safety: By leveraging WCG’s industry-leading institutional review board (IRB), institutional biosafety committee (IBC), and data monitoring committee (DMC) solutions, institutions can benefit from streamlined operational efficiencies and ensure appropriate safety and efficacy requirements are met. 

• Optimize Resource Allocation: Institutions can refine their resource allocation to focus on patient-facing activities, reduce the financial burden of research activities, and improve overall financial performance.  

• Build Strategic Resilience Thought Leadership: Research administrators and clinical research leaders will have the opportunity to join the conversation with WCG thought leaders at upcoming executive forums, webinars, workshops, and industry events beginning next week. These collaborative efforts will include sharing best practices and examining real-world stories of institutions that have successfully advanced their research while navigating funding constraints. 

“At WCG, we understand the critical role that financial stability plays in the advancement of clinical research, and we know it will take all of us working together to help solve this industry challenge,” said Sandra Smith, senior vice president, Clinical Solutions and Strategic Partnering, WCG. “We’re committed to help institutions navigate these challenges by providing them with the tools, insights, and support they need to continue driving groundbreaking research that brings life-saving treatments to patients sooner.” 

By helping institutions build resilience and maintain their research momentum, WCG is committed to fostering a future where financial limitations do not hinder the progress of essential clinical research. 

For more information on how WCG can support your institution in navigating financial challenges and optimizing research operations, visit https://www.wcgclinical.com/solutions/site-enablement/. 

The post WCG Announces Research Resilience Solutions to Navigate Institutional Budget Constraints  appeared first on WCG.

Watch our webinar for research sites and institutions as we dive into actionable strategies for expediting study activation and study start-up timelines. Gain insights into how operational silos during study activation can adversely impact start-up timelines and compliance, slow research progress, and potentially jeopardize study outcomes. Explore a more streamlined and integrated approach that improves trial efficiency and participant care with experts from Yale Cancer Center and WCG.

View this webinar to gain valuable insights into:  

• Proven strategies for accelerating study activation timelines. 

• How to fix silos in your study activation before they impact your timelines and compliance. 

• Understanding the effects of study activation processes on participants. 

Speakers:

Adam Roshka

Director of Finance and Operations, Yale Cancer Center

Juliann Murphy

Assistant Director of Clinical Trials, Yale Cancer Center

Jody Ingebritsen-Howe

Director of Site Contracts and Budgets, WCG

Sarah Garner

Senior Manager of CTMS Services, WCG

Jessica Thurmond

Program Director, WCG

The post Accelerating Study Activation: Breaking Down Silos for Start-up Success appeared first on WCG.

WCG ClinSphere™ Total Feasibility doubles site feasibility response rates compared to the industry average and significantly reduces timelines and burdens for both sponsors and sites during the site evaluation and selection process. Users now have an option of self-service or high-touch experience with wrap-around services, providing clinical development insights and site identification for end-to-end study start-up support.

“On average, sites spend 200 hours per month completing feasibility activities, and up to 87% of questionnaires are considered redundant,” said Cristin MacDonald, vice president, Client Delivery, WCG. “Our solution automates and streamlines these processes, allowing research teams to focus on new and critical information, ultimately enhancing study success and accelerating timelines.”

“WCG ClinSphere™ Total Feasibility revolutionizes the study start-up process,” said Sam Srivastava, chief executive officer, WCG. “By integrating comprehensive data combined with user-friendly tools, we empower research teams with the insights they need to make informed decisions quickly. This innovation is central to our mission to improve lives by accelerating research, bringing life-saving treatments to patients sooner.”

Key features of WCG ClinSphere™ Total Feasibility include:

• Enhanced Investigator and Site Profiles: Utilizing the power of WCG’s extensive data, surveys are pre-populated to reduce site workload and accelerate responses. With more than 300 standardized fields, users can access comprehensive details on site capabilities, staff, and logistics.
• Data-Driven Decision Support: Leveraging information from proprietary, robust data, the application offers unique insights, streamlining the assessment process to find the best-fit investigators and sites for each study.
• Interactive Dashboards and Real-Time Tracking: Sponsors have immediate access to progress and status updates through interactive dashboards. Real-time tracking, scoring, and response analysis enable rapid decision-making.
• Integrated Feasibility Solutions: WCG’s Total Feasibility solution minimizes redundancy, speeds results, and improves collaboration, reducing the workload for sites and providing faster turnaround times.

For sponsors and CROs, the new self-service capability offers a valuable tool to streamline operations, reduce costs, and improve relationships with sites during the feasibility process for their clinical trials. This launch represents a significant advancement in WCG’s comprehensive suite of solutions designed to support the entire clinical trial lifecycle.

For more information on WCG ClinSphere™ Total Feasibility, visit https://www.wcgclinical.com/technologies/total-feasibility/

The post WCG ClinSphere™ Total Feasibility Releases Self-Serve Capabilities that Optimize Clinical Trial Site Selection appeared first on WCG.

In this episode of WCG Talks Trials, join Silvio Galea, chief data and analytics officer, WCG, and Melissa Hutchens, vice president of research and benchmarking, WCG, as they discuss the transformative role of AI in clinical trials. Discover how generative AI and other AI machine learning technologies are enhancing the quality of clinical trials, reducing cycle times, and cutting costs. The episode covers the benefits, barriers, and concerns associated with AI, and explores its applications in drug discovery, trial design, participant recruitment, and more. Tune in to learn about the latest advancements in AI and how they are shaping the future of clinical trials.

The post AI in Clinical Trials: Unlocking the Potential appeared first on WCG.