Funding Opportunity Description - JHU

Funding Opportunity Description

Background

The Johns Hopkins University School of Medicine has created the Center for POCTR for STDs under an award from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) to coordinate development, clinical evaluation, and reduction to practice of new point-of-care (POC) devices. This Center is a collaboration between the Johns Hopkins University School of Medicine, the Johns Hopkins University Applied Physics Laboratory, the Infectious Diseases Institute at Makerere University College of Health Sciences in Uganda, and the Cincinnati Children’s Hospital Medical Center. The technologies are intended to bridge the gap between current biomedical sensors used in laboratory or research settings as opposed to those used at the bedside, in the clinic, or in a home care scenario.2 Specific test characteristics related to the operating environment proposed for the test are described below. 

The goal of the Center for POCTR for STDs is the development of integrated systems that address unmet clinical needs for STDs that can be solved through POC testing3,4. The need to develop sensitive, specific, and more easily available POC technologies for diagnosing sexually transmitted diseases is critical. These infections are particularly problematic in women. Most STDs in women are asymptomatic and only detected through routine screening or when women present themselves for testing after being notified of infection in sexual partners or because they perceive themselves to be at-risk. Five of the top ten reportable diseases to the Centers for Disease Control and Prevention (CDC) in the United States are STDs5.

POC diagnostics may include tests that are used in various settings. The following total assay times (TAT) have been derived by our Center based on average patient visit times. Therefore, POC diagnostic characteristics proposed for different operating environments, as described below, may vary2,6. For example:

  • The Emergency Department (ED) preferred time from sample to result is based on a patient visit time of four hours or less and could use commercial power (120V in U.S.).
  • A community clinic, non-traditional, or urgent health care setting (UC) preferred time from sample to result is based on a patient visit time of less than one hour and could use commercial power (120V in U.S.).
  • The home use POCT (HT) preferred time from sample to result should be less than 15 minutes and is based on user preferences from focus groups and could use commercial power or batteries.
  • There is an additional need for POC tests for low-resource settings (LRS). While the requirements can vary by location, in general the time from sample to result is preferred to be two hours or less and should use batteries as commercial power may not be consistently available. Hence batteries that can be recharged are preferable to batteries which are single use.

It should be noted that the users (the people conducting the POC tests) may be significantly different in each of these scenarios and may include medical doctors, other trained health professionals, or lay people without medical backgrounds. In its planned use, the test should not require performance by a clinical laboratorian.

Research Objectives

While the types of POC technologies considered will include both novel detection technologies and novel enabling technologies, this solicitation is seeking primarily to provide “tactical” funding to develop or improve on novel detection technologies. Detection technologies are defined as technologies in which the device is able to identify and discriminate the infectious agent using a clinically relevant sample. Enabling technologies are defined as technologies which can be used with currently available diagnostic rapid tests to improve and simplify sample preparation or rapid development of new specific reagents (antibodies, aptamers, etc.) for use in existing detectors with potential to be transferred into a health care setting or home use.

“Tactical” funding is directed to a critical experiment(s) which, if successful, would

  1. provide preliminary data
  2. enable first demonstration
  3. verify proof of principle/concept or
  4. complete a seedling effort to enable organizations to seek additional funding for more robust technology development.

These awards are narrow in scope, but should open the path to more robust and detailed development or integration of detection and/or enabling technology.

Technologies considered for award will include the following features

Current test is able to detect the STD(s) of choice (with exclusion of Zika virus), viral load determination for HIV, or functional evaluation of multidrug resistance.

Preference is given to tests which discriminate syndromically related STDs such as Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, or Mycoplasma genitalium. These organisms are listed as examples only. Other organisms that cause STDs will be considered.  

Detection can be achieved by:

    a) Detecting genetic or protein based components of the organism  
    or 
    b) Detecting combinations of general optical or electrical characteristics which can be determined to be unique to the organism 
    or 
    c) Detecting surrogate markers as long as the clinical significance of the surrogate marker is well established

Wherever possible and appropriate, applicants should address how the institution currently achieves or expects to achieve performance metrics required for POC technologies for STDs. Evaluation of detection technologies under consideration for award will include an assessment of the following technology performance metrics6:

  • Achieves an analytic detection of low numbers of target STD. This value will vary according to the STD selected for detection.
  • Achieves a sensitivity ≥90% when compared to the current clinically accepted assay
  • Demonstrates greater specificity to the target organism compared to expected confounding or commensal organisms
  • Demonstrates a detection time from sample collection to result in 90 minutes or less in a relevant operational setting (ED, UC, LRS, or HT)
  • Demonstrates successful implementation by an inexperienced user, such as a non-laboratorian, when training is provided
  • Should not include more than 3 steps (exclusive of sample acquisition)
  • Must be prepared for storage at room temperature or 4ºC for at least 6 months
  • Assay answer /readout must not be subjective
  • Provides single sample format for at least one organism
  • Tests include all necessary controls for quality assurance and assay performance

Other General Notes about the Research Objectives

  • Proposals that describe conceptual ideas or theoretical detector data are not within the scope of this proposal.
  • Proposals that describe component systems which have not been integrated or breadboard systems with preliminary results are eligible under this solicitation but applicants must describe specifically how they intend to reach the developmental level required to participate in testing of clinical samples in future years.
  • Proposals that describe devices based on detection of surrogate markers will be considered as long as the clinical significance of the surrogate marker is well established or supported in the proposal.
  • Proposals using component-based systems where some of the components are already in use in food, medical, or environmental markets should emphasize which components are under development and which are novel developments.
  • While preference is given to proposals that can meet the needs of the POC testing market selected by the applicant and are inclusive for resource-limited settings, proposals are preferred which can meet the needs of multiple user markets from the examples listed (i.e. ED, UC, LRS, and/or HT).
  • The development award can be used to modify an existing laboratory developed test for use in an urgent care clinic or home market.
  • Batched assays which can be developed for single use assays are acceptable under this proposal.
  • Size, weight, and storage conditions of assay reagents are not restricted for entry into clinical evaluation.
  • All devices must work with standard power (120V) or batteries.
  • Battery-powered devices should be rechargeable.

Further details about successful test characteristics

Successful technologies must demonstrate detection of important STDs, (e.g. Chlamydia trachomatis or other, as described above). Comparative measures of sensitivity will vary by organism8. However, for the example of Chlamydia, a successful technology would be expected to achieve an analytic detection of less than 1,000 elementary bodies/ml when presented in relevant diluents, which include phosphate buffered saline, DEPC treated water, or TRIS borate buffer. Other acceptable measures of sensitivity would be technologies that achieve a sensitivity ≥90% when compared to the current clinical reference standard. For Chlamydia, the current accepted clinical reference standard is a vaginal or urine nucleic acid amplification test (NAAT), according to the CDC9. The test must show high specificity of the organism compared to expected confounding or commensal organisms. For the example of Chlamydia trachomatis, the technology would be expected to differentiate between C. trachomatis, C. pneumoniae and C. psittaci. Similarly, an assay for Neisseria gonorrhoeae should not detect non-pathogenic neisseria, such as N. subflava, N. cinnerea, N. lactamica, etc. Another measure of specificity is a technology that achieves >97% specificity compared to the current clinical reference standard. It is expected that the pre-clinical development will include testing the device versus known dilutions of cultured organisms in order to determine the limit of detection (LOD).

Multiplex detection technologies are desired which can discriminate Chlamydia from other important STDs including Neisseria spp., Trichomonas spp., Staphylococcus spp., Acinetobacter spp., and Candida albicans. Additional second tier infections of interest to distinguish include Treponema pallidum, Haemophilus ducreyi and Herpes Simplex virus (HSV). Successful technologies will achieve an analytic detection limit for Chlamydia of less than 1,000 organisms/ml when presented in a relevant diluent as described above. If required for the success of the detection technology, protocols for sample concentration must be included as part of the assay protocol.

Protocols for use of the detection technologies should be written to eventually accommodate users with at least an 8th grade reading level. Protocols may be supplemented by up to one day of training for inexperienced users.

Assay readout must not be subjective but be easy to read using color change readout, digital or graphic formats. Tests which require the user to interpret single color variations are not acceptable. Tests must include controls for interpretation of positive and negative values and a control for verification of assay performance. Proposers should have the ability to provide at least 500-700 individual tests and at least two testing (i.e. reading) devices (if required by the assay) for subsequent clinical evaluation. There are no requirements regarding the final size or packaging of the device at completion of funding.

Review Process and Criteria

Proposals which are responsive will specifically address the items noted in the sections above as appropriate. All reviewers and Center staff with access to proposals have completed conflict of interest and non-disclosure agreements ensuring the confidentiality of the proposal. Applications will be reviewed by at least 3 independent scientific reviewers, outside of the Center staff, who will judge the application based on scientific merit and proposed milestones/deliverables. Brief monthly progress reports and a detailed final report from awardees will be required by JHU APL, the contracting organization.

Full proposals will be evaluated for the following:

  • Scientific and technical merit
  • Appropriately scoped to the amount of funding and period of performance requirements of this solicitation
  • The ability to fulfill the specific research objectives as stated above
  • Significance and relevance to the mission of the Center for POCTR for STDs
  • Pre-analytical efficiency and rapid analytical speed of assay using laboratory strains
  • Sensitivity and specificity compared to gold standard results
  • Potential to apply technology to common STDs using multiplex diagnostic testing
  • Limit of detection
  • Ability of the point-of-care test to require storage not lower than 4ºC
  • Appropriate quality assurance provision (e.g. assay and device controls, within performance/calibration controls for devices)
  • Competence and experience of the investigative team
  • Bioengineering and research environment in which the work will be performed
  • Likelihood of success when used in one of the scenarios identified as physicians’ offices, Emergency Departments (EDs), low resource medical facilities, home care or community clinics by minimally trained staff
  • Practical suitability for use in near-patient applications in ED, clinic, or home care settings
  • Incorporation of testing principles or assay improvements that can be reduced to one or more operating prototypes within the next two years.
  • Plan for effective evaluation of the diagnostic method using archived clinical samples

General Award Information

Awards will be for six months or less. A technology monitor from JHU APL will meet with successful awardees monthly to review progress and achievement of critical milestones and deliverables. As required by NIBIB, our Center will track the progress on an award using the GAITS (Guidance and Impact Tracking System) platform to track funded projects using a common mechanism within the POCT Research Network.

GAITS is based on the Healthcare Innovation Cycle and structures work packages in deliverables and milestones. Each deliverable and milestone should reference its association with one of 10 “Maturity Levels” and one of four “Domains” (Clinical, Market/Business, Regulatory, and Technology) as indicated in the figure below. This document provides a check list for use in addressing GAITS.

It is important to note that a single $50K award is not expected to address all of the maturity levels or all of the domains shown above especially since proposals should have achieved at least technological TRL 3 by the time of application (proof of concept).

A second six month award for technologies that are successful in their first period of performance will be considered if needed. The first award must be completed before a second award can be negotiated; however, it is permitted to apply for a second award in anticipation of completing the first award by the time the new proposal is reviewed.

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