Case Studies

• The Study: We sought to compile a large, academic medical center-based historical dataset to clarify clinical outcomes in the second line or later among patients with KRAS G12C mutant NSCLC in a multicenter (13 sites) retrospective Chart Review analysis of clinical outcomes of real world evidence (RWE) among 396 patients with KRAS G12C mutant non-small cell lung cancer.
   
• The Problem: There is a paucity of real-world data describing clinical outcomes in patients with locally advanced or metastatic KRAS G12C mutated NSCLC in the second-line or later, as most prior studies featured outcomes in the first line setting.

• The Challenge: The sites provided by Criterium/ATOMIC (Academic Thoracic Oncology Medical Investigators Consortium) were able to provide the resources and effort to abstract information from the charts in a format compatible to the sponsor’s other collected data by deadline. This result provided critical real world data (RWD) to corroborate comparative data obtained in the sponsor’s prospective clinical trials.
   
• The Results: We observed a real world first line progression free survival of 9.3 months and overall survival of 16.8 months. We also observed a second line real world progression free survival of 8.3 months in all patients, but only 4.6 months among patients treated with docetaxel containing regimens in the second line.

Read More on the complete study results.

Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC)

A Multicenter Retrospective Chart Review of Clinical Outcomes Among Patients With KRAS G12C Mutant Non–Small Cell Lung Cancer

• Scenario: A patient with HR+/HER2+ metastatic breast cancer is evaluated in medical oncology clinic. The patient received first line docetaxel, trastuzumab and pertuzumab, and second line T-DM1 for treatment of metastatic disease.

Latest restaging imaging studies showed progressive disease and new CNS metastases. The standard of care therapy will be HER2CLIMB regimen (tucatinib, capecitabine, trastuzumab) or T-DxD after stereotactic radiation to the brain metastases.

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• What If: The patient tired of infusions, does not want to go on chemotherapy-based regimen, and is asking if any oral treatment is available that does not have chemo-induced side effects?
   
• Results: Treatment was well tolerated. ABRCC/Criterium reported results of a phase IB/II trial of an all-oral combination of the HER2 inhibitor Tucatinib, aromatase inhibitor Letrozole, and CDK4/6 inhibitor Palbociclib (TLP) for treatment of HR+/HER2+ metastatic breast cancer:

• • Median progression free survival (mPFS) was 8.4 months, with similar PFS in the cohorts of patients with and without brain metastases (8.2 and 10.0 months, respectively, p=0.9).
  • Overall response rate was 44.5%, median duration of response was 13.9 months, clinical benefit rate was 70.4%. Sixty percent of patients were on treatment for ≥6 months, 25% for ≥1 year, and 10% for ≥2 years.
  • In the CNS cohort, 26.6% of patients remained on study for ≥1 year. Future trials of TLP combinations are warranted based on the tolerability and clinical activity of the regimen.

Read More on the complete study results.

Academic Breast Cancer Consortium (ABRCC)

Safety and Efficacy of Tucatinib, Letrozole, and Palbociclib in Patients with Previously Treated HR./HER2. Breast Cancer

• Scenario: A Phase II NDA trial with 4 expert sites, in 4 countries enrolled 80 patients, in less than four months for outstanding clinical results.

The client decided to conduct this study outside of the US so they would not need to submit the study to the IND.

Our international field, data accession, and consultant team selected and managed 1 site each in Ecuador, New Zealand, South Africa and Sweden. The team enrolled the required number of patients in 16 weeks. The data were transmitted in real time to Saratoga Springs, NY, where the database was closed within two weeks. This information was provided to our statistical group, which completed the analysis and final clinical study report ahead of schedule.

• What If: The deadline for this product was critical. In principal, they needed to finish the study for their development partner before they completed the preclinical safety dossier.
  
  
• Results: Criterium saved more than three months and met the client’s deadline for corporate evaluation of the product.

• Scenario: A Phase III study required by the FDA for approval was stalled at its North America sites and regulatory processes in South America prevented significant contribution to these studies. There were multiple rejections because this infectious disease study required a placebo control. The study recruitment by another CRO was not met in the previous two seasons.

Criterium offered an experienced team in the Southern Hemisphere to get approval by the regulatory authorities of this placebo-controlled respiratory infection study, to extend the recruitment to 10 months of the year and to enroll at a higher rate per site than the previous seasons’ site enrollment rates.

Criterium’s team averaged more patients per site than the Northern Hemisphere at a high compliance rate for the target micro-organisms.

• What If: The client could have continued recruiting patients in the Northern Hemisphere winters, thereby further extending the length of the study.

• Results: Criterium managed the regulatory process to receive approval for the study on the first agency reviews and accelerated enrollment with its experienced team in South Africa and New Zealand.

• Scenario: Criterium provided regulatory support, 75 sites and organized two investigators meetings for this Phase III, 700 patient study.

Criterium experienced teams in South Africa, Russia and Ukraine met with the agencies and the Ethics committees to expedite approval of this protocol during the first of each of their regulatory cycles.

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• What If: Lagging or non-approvals would have meant that additional submissions would have been required and the duration of patient enrollment would have increased.
  
  
• Results: The start of this study exceeded the client’s expectations.

• Scenario: A pivotal NDA trial using 60 sites, 592 patients, and a timeline of less than four months for the clinical study.

The client was in danger of missing its deadline because of a protracted RFP process in choosing a CRO.

Our international field, data accession, and consultant team solicited sites in South Africa. The team enrolled and evaluated the required number of patients in 12 weeks. The data were transmitted in real time to Saratoga Springs, NY, where the database was closed within two weeks. This information was provided to our West Coast consulting group, which completed the final clinical study report ahead of schedule.

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• What If: The deadline for this product was critical. Had the client missed the submission date, the sponsor would have had to make a decision whether to continue developing the product.
  
  
• Results: Criterium saved one month and met the client’s deadline for FDA submission.

• Scenario: A Phase IV study was required by the FDA as a condition of approval of an orphan drug. The sponsor was faced with monitoring, managing, and locking data for a 12-month study conducted at 100 sites.

Criterium offered an integrated technology-enhanced solution that allowed the sites to register patients and allowed the patients to record their event data directly into our remote systems.

Criterium’s solution enabled the client to eliminate most of the scheduled monitoring visits. Criterium’s diligence and centralized system meant that monitors only had to visit sites that had problems.

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• What If: If the client had used traditional methods, the cost would have soared for a product that has modest revenue and it would have taken much longer to provide the data to the FDA and the prescribing community.
  
  
• Results: Criterium’s centralized real-time data accession utilizing Automated Fax Scanning (FAX) and Interactive Voice Response (IVR) medical history and patient diary application saved the client $1 million to $1.5 million in clinical monitoring and data management costs. In addition, the data were provided to the medical community and were satisfactory for rapid submission to the FDA for conditional approval.

• Scenario: Criterium provided an IVR patient diary solution to collect the pivotal efficacy data for an international clinical trial.

Because the estimated patient compliance rate was critical for the statistical analysis, Criterium daily monitored the patient diaries.

Through StudyControl™, Criterium designed reports to evaluate the compliance of each patient during the study. When patient compliance was less than predicted, Criterium informed the client immediately. This critical intervention enabled the sponsor to enroll additional patients into the study. Additionally, daily management of the site by Criterium’s knowledgeable staff members helped ensure that patient compliance among the additional study participants was at the highest level, thereby meeting the study’s control requirements.

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• What If: An after-the-fact paper patient diary could have been disastrous and could have necessitated the client repeating the study.
  
  
• Results: The statistical analysis exceeded the client’s expectations.