The organization should have proprietary information about what is effective and ineffective for recruitment. They should ideally also have in-house creative capabilities, patient advocacy relationships, and technology that can bring to life even the most complicated strategies. And beyond a stellar understanding and experience of marketing clinical trials to patients, these teams should have a legacy understanding of how to work with stringent and difficult IRB review processes and internal reviews.

They should be able to take input from the patient community, pair the feedback with robust datasets, and leverage the information to create marketing materials that engage potential applicants while also optimizing for a speedy approval by the IRB and other regulatory teams. The right vendor should also have the capability to help you in pushing these recruitment materials to finish the line internally within your organizational structure.

Clara Health: At Clara Health, all of our recruitment efforts are powered by a highly experienced in-house marketing team that knows the ins and outs of clinical trial recruitment. With a combined advertising experience of over 35 years, our marketing team is skilled in digital omni-channel clinical trial recruitment, while our patient advocacy team supports the grassroots and community level patient recruitment.

By combining our patient-focused internal infrastructure and expertise in digital and offline patient recruitment, we are able to reach your desired patient population in the right place, at the right time, and with the correct messaging and patient-first branding that allows us to actualize the enrollment potential for your study.

We are constantly building our own database of proprietary data that give us a real understanding of recruitment difficulty across various therapeutic areas.

If you would like to get a better understanding of the expected recruitment difficulty for your clinical trial, we offer a Free Recruitment Difficulty Assessment based on our proprietary data in your therapeutic area.

It is helpful for a patient recruitment partner to have worked with your exact condition in the past, as the vendor will already have the data and experience to understand all the potential problem areas for recruitment.

It is also helpful if the vendor you are considering has done patient recruitment for a similar patient population, or for conditions with similar rarity. The right vendor will be able to accurately predict the potential pitfalls for recruitment in any therapeutic area regardless of previous experience, as well as ground the expectations for the recruitment difficulty levels through a combination of general expertise and their variety tools for testing your target patient population.

ClaraHealth: We are constantly running tests and building our proprietary data across various therapeutic areas. This data allows us to have an in-depth understanding and expectations of how difficult it is to recruit for specific patient populations, as well as which particular segment of the patient population is likely to enroll in a particular study.

If you are running an international trial, you would want to know if the recruitment agency has experience in running international trials and if they are compliant for handling patient data in accordance with the data privacy policies across different regions.

The difference in language is not typically a major area of concern, as most vendors will have processes in place to be able to professionally translate any marketing assets in a way that will resonate with the specific international regions.

ClaraHealth: We have previously provided patient recruitment services for studies in the EU, Canada, UK, Australia, and South America. ClaraHealth is fully compliant to run international trials everywhere in the world, outside of China and Russia.

The details of how this will be done, and whether or not you will incur an additional fee for referrals to other trials in your portfolio will be individual to every vendor. The right recruitment vendor for your studies should have the flexibility within their financial structure and their company infrastructure to accommodate this request, should you happen to be in a situation where you are running several trials within the same disease sphere at the same time.

ClaraHealth: For sponsors running multiple trials within the same indication, our platform can automatically match patients to different trials via our patient support team to create a seamless experience for the patient and assist you with your global recruitment goals.

More commonly, we face the scenario where sponsors are running a single trial, and strive to deliver the exceptional patient experience that the applicants deserve. For patients who do not meet the qualifications criteria for our partner trial listings, our patient support team continues to assist them in finding another trial that fits them - whether that be in the form of being provided a list of alternative trials, or providing wraparound support to find the trial they need.

This practice is excellent for both patients and sponsors, as it allows patients to have an amazing overall experience with the sponsors that we represent. Oftentimes, these patients go back to their unique patient communities and share their experience of receiving help all the way through rather than being dropped all of a sudden upon not meeting the qualifying criteria.

This ensures that the sponsors we help are perceived well in the community, and helps to improve their brand perception. When getting ready to set your clinical trial to launch, timelines can be quite demanding and every single day counts significantly.

Each day that the trial is delayed to start can cost sponsors several hundred thousand and in some cases, over one million dollars in operational expenses and potential losses from delays in the commercialization of their investigational drug, so time becomes a very valuable and finite resource.

In other cases, sponsors may be falling behind their recruitment timelines, and rescue support must be dispatched as soon as possible. For these reasons, the ideal patient recruitment will be one that does not delay you in any timelines. Your recruitment vendor should have maximum flexibility with how quickly they are able to develop their materials and recruitment strategy.

Helping you to meet these tight timelines should be one of the most important priorities for the recruitment vendor, and they should have the infrastructure and capacity to operate in a way that allows them to get things up and running as quickly as your situation requires.

Clara Health: For us, our timelines are typically most constrained by how long the IRB review process is going to be. We are typically able to match any timeline, and have the internal capability to go at the pace that helps to achieve the timeline goals and objectives of our partners.

One of the most important determinants of the level of success for a study recruitment campaign is the screening flow for potential trial participants. The ideal recruitment partner will be able to create a frictionless screening experience for patients that robustly qualifies the patients while aiming to maximize the rates of screener completion.

This implies that the partner has the ability to thoroughly analyze the target patient population, and understand what screening process will be suited best for helping to qualify patients and form it into an accessible, pleasant and easy experience.

Screening flow design is a common pitfall that can make or break your ability to meet your recruitment goals, and therefore you want to be certain that the potential recruitment partner is a complete expert in designing high-converting and easy-to-complete screening flows.

The ideal design breaks up the flow into manageable slices; for example, an initial digital screener may ask simpler qualification questions and be followed by a more robust phone screener.

In the case of poorly designed screening flows, patients typically come face-to-face with a form that attempts to take them through the entire qualification process in one large step. The consequences of a screening design that is completely stripped of human touch, is that patients often end up abandoning the application forms mid-way or lose motivation to take next steps, even if they complete the initial applications.

By attempting to do too much at once, a sponsor can incur otherwise avoidable expenses, while losing potential enrollees along the way. Clara Health: When it comes to designing the screening flow for our partners, we begin by doing a thorough research into the target patient population.

After understanding exactly who and which communities we are going to be working with, we typically fragment the screening process into a digital screener and a phone screener.

Within the digital screener stage, patients are asked broader and less personal questions to ensure that they will be mostly qualified while also keeping the screener form as short as possible to optimize for full completion.

In the phone screening stage, more specific and personal qualification questions are asked. For very complex conditions, our platform is also able to consolidate EMRs for applicants and screen against details within those records. This three-step screening process allows us to robustly qualify the patients, while also creating a patient experience that is more manageable, supportive, and motivating than confronting applicants with a convoluted and challenging screener.

Our patient support team welcomes and makes applicants feel comfortable and well taken care of, and in turn this increases the likeliness of them sharing more specific information.

In addition, our patient support team is able to hear and respond to real-time feedback, and create a high-quality and truly personal experience based on the individualities of every applicant that goes through this stage. It is impossible to be able to fully predict how the recruitment process for a clinical study will unfold with complete certainty prior to beginning the campaign.

There are always factors that will either be left unaccounted for, or will show up in the form of unpredictable situations. The processes that go into patient recruitment are complex and vary according to the individuality of the target patient population for the clinical study, as well as based on the study design itself, which also varies from study to study.

Given this individuality of each study, and the uniqueness of corresponding approaches for recruitment, it is important to understand exactly how the potential recruitment partner has handled challenges as they came up in the past. The goal of this analysis is to understand how efficiently the recruitment is able to adapt to unpredictable situations within recruitment, as well as to understand what their financial implications are when working with a particular partner.

Some questions to help you understand how challenges are handled by a potential recruitment partner include:. What you're looking for in a recruitment partner is somebody that is able to give you a consultative perspective and proactively provide guidance to steer recruitment to success.

A reactive partner that only creates changes under your pressure will slow you down and neglect core issues that you may simply not be able to respond to on time. Therefore, it is important that you find somebody that is able to respond to issues right away and keep you in the loop while doing so.

This gives us the unique ability to quickly address any issues that may arise, and if needed, to connect with our sponsors to provide consultative feedback and let them know our next steps. Given our unique position right in the middle of patients, sites, and internal sponsor teams, we are able to constantly gather valuable information, which helps us to predict with more accuracy what potential issues may come up later in the recruitment process and address them before they become significant or can affect results.

Some companies may specialize only in patient recruitment, or only in patient retention. If you require both services for your trial it's highly recommended to find a vendor that is able to perform both of these services. There are clear advantages to this consolidated model that reflect both in the patient experience and in your overall costs.

Firstly there is higher operational efficiency when a vendor is able to support both services, as the same service teams will typically handle patients for either recruitment or retention. This means that certain resources within the vendor company are set up simultaneously to perform both services, which makes it cheaper compared to hiring another retention vendor that would have to set up entirely new frameworks to do their work.

However the larger advantages are seen in the seamlessness of the patient experience, as you're able to have a single centralized support team that sticks by the patient's side all throughout their participation in the trial.

This bridges many communication gaps between you and study volunteers that are a result of a recruitment vendor handing off patients to a retention vendor. Another advantage of having a single vendor to support both services is having someone with the ability to determine, measure, and report on key metrics for both services.

This gives you the ability to unite all the measurements and have an overall, integrated understanding of exactly how your patients are enrolling and participating in your trial.

While it is possible to consolidate reporting from two vendors, this is an extra step that you may be able to avoid by finding a partner that will perform both services for you and provide reporting that takes into account the entire recruitment picture. Clara Health: Our patient recruitment and retention models are centred around a seamless patient experience, with our patient support team at the heart of the entire process.

At some point a patient touches base with our support team that guides and fully assists the patient to set up visits, logistics, reimbursement, or anything else that is required for the patient to be able to comfortably participate.

We remove all obstacles within our control that otherwise would have prevented someone from participating in the study. Our centralized patient support also allows us to build trust with the patient community on behalf of your brand. Patients sense that they are treated with care and that the same team that helped them enrolled in the trial will also help them to participate in that as well.

We have a deep understanding of the entire patient journey when contracted for studies for both recruitment and retention services, and are able to get clear metrics on how the entire enrollment process is unfolding, which allows us to identify challenges early through seeing more complete data.

The type of reporting, the cadence at which you receive it, and its inclusion of all the critical metrics can significantly impact your understanding of how your trial is progressing in recruitment, and with that your level of responsiveness for making important decisions.

For this reason, we advise that you get a crystal clear understanding of the expectations for reporting. Most patient recruitment companies will provide reporting via an older approach sending formal reports or the modern approach via live dashboard.

This means that instead of having delays of days or with some vendors up to 2 weeks , your data is continuously updated and you can access it at any time. Dashboard reports also allow you the ability to interact with the data in front of you, by giving you the ability to compare specific date periods or relating the recruitment factors that you are most interested in seeing.

Some Foundational Reporting Metrics For Most Recruitment Processes Include:. ClaraHealth: We provide all of our clients with access to a dashboard that is updated as closely as possible to real-time. It is important to know how patient-oriented the potential recruitment vendor is, because it is a significant determinant of their ability to succeed in helping you with patient enrollment.

A recruitment vendor with close and authentic relationships to the patient community typically has a deep understanding of how to best serve these patients to create an amazing recruitment experience.

In addition, vendors that work alongside patients are able to create more engaging and comprehensible recruitment materials, as they are able to receive vital feedback regarding the recruitment language and creatives to be used in recruitment campaigns.

It also allows the vendor to consult real patients to accurately target the demographic after determining the ideal patient personas based on received feedback. Another significant benefit of having a strong relationship with patient communities in a vendor is that it allows you to tap into their patient advocacy networks to spread the word about your clinical trial, opening up an additional ultra-targeted recruitment channel.

Patient recruitment vendors that have weak relationships with patient communities simply do not have access to these benefits, which are so helpful for recruitment in trials for broad conditions, and a complete necessity for rare disease trials. Clara Health: We have a dedicated patient advocacy team that has been with us since the very beginning.

Our products, platform, services, and teams all work in the service of the patient. We also have the capability to build partnerships in an authentic way, such that we can reach into patient communities on behalf of a pharmaceutical company, giving our partners the opportunity to start a conversation with patients through our patient advocacy team in a trusted fashion.

Over the last couple of decades the FDA has made a focus on promoting recruitment practises for clinical trials that would lead to the best reflection of the population that would most likely use the medication. It is important that the recruitment vendor has a thorough understanding and a marketing strategy in place that would reflect diverse patient recruitment practises, as this is both a best practice and a risk factor that could potentially prolong the treatment from coming to the market, or getting FDA approval altogether.

However this practice skews the data set, as the treatment gives good results in only one type of the patient population group, while under-representing another group. It is important to test the treatments on a diverse population to avoid harming other untested populations in the future.

And, the less representation there is of all the groups that would be using the treatment, the less likely it is that this treatment would work for the patients that would actually be using it. As a sponsor, you are typically bound to the study sites for the majority of your recruitment traffic.

This is a significant challenge, because sites may not have lists that would be inclusive of the patient population that should be represented in your clinical research. Clara Health: With our omni-channel marketing approach, we are able to tap into diverse pockets of traffic to reach specific patient populations.

We do this by building a patient diversification recruitment strategy that allows us to reach patients representative of specific groups, by utilizing a mix of digital recruitment combined with patient advocacy outreach. In addition, we are also able to generate new partnerships with specific patient communities that increase our effectiveness in diverse recruitment.

Finding a partner that specializes in recruitment channels that you do not have access to, or expertise in, allows you to maximize your coverage and make sure that patients are able to learn about your trial wherever they are. Understanding of how your vendor is planning to recruit patients for your study will also show the level of diversification within the recruitment strategy.

A more diversified recruitment strategy helps you to reduce your risks, as you are able to experiment with different recruitment channels and have more room to scale your recruitment efforts if needed.

For example, if you are planning on only using study site lists for recruitment, this strategy may yield results in the short-term, but would potentially be difficult to scale. Once the list of patients becomes exhausted, recruitment may stagnate and you risk falling behind your timelines and recruitment goals.

Clara Health: When designing a recruitment strategy for our clients, we start by conducting extensive research into the target patient population to understand exactly which recruitment channels will work best, as well as what kind of marketing materials are needed to maximize results.

Article PubMed Google Scholar. Parmar MKB, Barthel FMS, Sydes M, Langley R, Kaplan R, Eisenhauer E, et al. Speeding up the evaluation of new agents in cancer. J Natl Cancer Inst.

Article CAS PubMed PubMed Central Google Scholar. Zohar S, Chevret S. J Biopharm Stat. Sverdlov O, Wong WK. Ther Innov Regul Sci. Maca J, Bhattacharya S, Dragalin V, Gallo P, Krams M. Drug Inf J. Stallard N, Todd S. Stat Methods Med Res. Chow SC, Chang M, Pong A.

Statistical consideration of adaptive methods in clinical development. Fleming TR, Sharples K, McCall J, Moore A, Rodgers A, Stewart R. Maintaining confidentiality of interim data to enhance trial integrity and credibility.

Clin Trials. Article PubMed PubMed Central Google Scholar. Bauer P, Koenig F, Brannath W, Posch M. Selection and bias—two hostile brothers. PubMed Google Scholar. Posch M, Maurer W, Bretz F. Type I error rate control in adaptive designs for confirmatory clinical trials with treatment selection at interim.

Pharm Stat. Graf AC, Bauer P. Maximum inflation of the type 1 error rate when sample size and allocation rate are adapted in a pre-planned interim look. Graf AC, Bauer P, Glimm E, Koenig F. Maximum type 1 error rate inflation in multiarmed clinical trials with adaptive interim sample size modifications.

Magirr D, Jaki T, Posch M, Klinglmueller F. Simultaneous confidence intervals that are compatible with closed testing in adaptive designs.

Kimani PK, Todd S, Stallard N. Lorch U, Berelowitz K, Ozen C, Naseem A, Akuffo E, Taubel J. The practical application of adaptive study design in early phase clinical trials: a retrospective analysis of time savings. Eur J Clin Pharmacol. Article CAS PubMed Google Scholar.

Bauer P, Bretz F, Dragalin V, König F, Wassmer G. Twenty-five years of confirmatory adaptive designs: opportunities and pitfalls. Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials.

Article PubMed PubMed Central CAS Google Scholar. Chevret S. Bayesian adaptive clinical trials: a dream for statisticians only? Jaki T. Uptake of novel statistical methods for early-phase clinical studies in the UK public sector.

Morgan CC, Huyck S, Jenkins M, Chen L, Bedding A, Coffey CS, et al. Adaptive design: results of survey on perception and use. Dimairo M, Boote J, Julious SA, Nicholl JP, Todd S. Missing steps in a staircase: a qualitative study of the perspectives of key stakeholders on the use of adaptive designs in confirmatory trials.

Dimairo M, Julious SA, Todd S, Nicholl JP, Boote J. Cross-sector surveys assessing perceptions of key stakeholders towards barriers, concerns and facilitators to the appropriate use of adaptive designs in confirmatory trials.

Hatfield I, Allison A, Flight L, Julious SA, Dimairo M. Adaptive designs undertaken in clinical research: a review of registered clinical trials. Meurer WJ, Legocki L, Mawocha S, Frederiksen SM, Guetterman TC, Barsan W, et al. Attitudes and opinions regarding confirmatory adaptive clinical trials: a mixed methods analysis from the Adaptive Designs Accelerating Promising Trials into Treatments ADAPT-IT project.

Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial.

J Am Med Assoc. Article CAS Google Scholar. Pushpakom SP, Taylor C, Kolamunnage-Dona R, Spowart C, Vora J, García-Fiñana M, et al. Telmisartan and insulin resistance in HIV TAILoR : protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy.

BMJ Open. Magirr D, Jaki T, Whitehead J. A generalized Dunnett test for multi-arm multi-stage clinical studies with treatment selection. Giles FJ, Kantarjian HM, Cortes JE, Garcia-Manero G, Verstovsek S, Faderl S, et al.

Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia. J Clin Oncol. Mehta CR, Pocock SJ.

Adaptive increase in sample size when interim results are promising: a practical guide with examples. Jennison C, Turnbull BW. Adaptive sample size modification in clinical trials: start small then ask for more?

Bowden J, Brannath W, Glimm E. Empirical Bayes estimation of the selected treatment mean for two-stage drop-the-loser trials: a meta-analytic approach.

Mason AJ, Gonzalez-Maffe J, Quinn K, Doyle N, Legg K, Norsworthy P, et al. Developing a Bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment. Wellcome Trust. Joint Global Health Trials scheme. National Institutes of Health.

NIH Planning Grant Program R European Medicines Agency. Reflection paper on methodological issues in confirmatory clinical trials planned with an adaptive design. Adaptive design clinical trials for drugs and biologics: guidance for industry draft.

Adaptive designs for medical device clinical studies: guidance for industry and Food and Drug Administration staff. Gaydos B, Koch A, Miller F, Posch M, Vandemeulebroecke M, Wang SJ. Perspective on adaptive designs: 4 years European Medicines Agency reflection paper, 1 year draft US FDA guidance—where are we now?

Clin Investig. Elsäßer A, Regnstrom J, Vetter T, Koenig F, Hemmings RJ, Greco M, et al. Adaptive clinical trial designs for European marketing authorization: a survey of scientific advice letters from the European Medicines Agency. DeMets DL, Fleming TR. The independent statistician for data monitoring committees.

Gallo P. Operational challenges in adaptive design implementation. Grant AM, Altman DG, Babiker AG, Campbell MK, Clemens F, Darbyshire JH, et al. A proposed charter for clinical trial data monitoring committees: helping them to do their job well.

Antonijevic Z, Gallo P, Chuang-Stein C, Dragalin V, Loewy J, Menon S, et al. Views on emerging issues pertaining to data monitoring committees for adaptive trials.

Sanchez-Kam M, Gallo P, Loewy J, Menon S, Antonijevic Z, Christensen J, et al. A practical guide to data monitoring committees in adaptive trials. DeMets DL, Ellenberg SS. Data monitoring committees—expect the unexpected.

N Engl J Med. Calis KA, Archdeacon P, Bain R, DeMets D, Donohue M, Elzarrad MK, et al. Recommendations for data monitoring committees from the Clinical Trials Transformation Initiative. Conroy EJ, Harman NL, Lane JA, Lewis SC, Murray G, Norrie J, et al.

Trial steering committees in randomised controlled trials: a survey of registered clinical trials units to establish current practice and experiences. Harman NL, Conroy EJ, Lewis SC, Murray G, Norrie J, Sydes MR, et al. Exploring the role and function of trial steering committees: results of an expert panel meeting.

Daykin A, Selman LE, Cramer H, McCann S, Shorter GW, Sydes MR, et al. What are the roles and valued attributes of a trial steering committee?

Ethnographic study of eight clinical trials facing challenges. He W, Gallo P, Miller E, Jemiai Y, Maca J, Koury K, et al. Zhu L, Ni L, Yao B. Group sequential methods and software applications. Am Stat. Tymofyeyev Y.

A review of available software and capabilities for adaptive designs In: He W, Pinheiro J, Kuznetsova OM, editors. Practical considerations for adaptive trial design and implementation.

New York: Springer: Gallo P, Chuang-Stein C, Dragalin V, Gaydos B, Krams M, Pinheiro J. Adaptive designs in clinical drug development—an executive summary of the PhRMA Working Group.

Quinlan J, Krams M. Implementing adaptive designs: logistical and operational considerations. Adaptive design methods in clinical trials—a review. Orphanet J Rare Dis. Bretz F, Koenig F, Brannath W, Glimm E, Posch M.

Adaptive designs for confirmatory clinical trials. Quinlan J, Gaydos B, Maca J, Krams M. Barriers and opportunities for implementation of adaptive designs in pharmaceutical product development.

He W, Kuznetsova OM, Harmer M, Leahy C, Anderson K, Dossin N, et al. Practical considerations and strategies for executing adaptive clinical trials. He W, Pinheiro J, Kuznetsova OM. Curtin F, Heritier S. The role of adaptive trial designs in drug development.

Expert Rev Clin Pharmacol. Petroni GR, Wages NA, Paux G, Dubois F. Implementation of adaptive methods in early-phase clinical trials. Sydes MR, Parmar MKB, James ND, Clarke NW, Dearnaley DP, Mason MD, et al. Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial.

Spencer K, Colvin K, Braunecker B, Brackman M, Ripley J, Hines P, et al. J Diabetes Sci Technol. Miller E, Gallo P, He W, Kammerman LA, Koury K, Maca J, et al.

Schäfer H, Timmesfeld N, Müller HH. An overview of statistical approaches for adaptive designs and design modifications. Biom J. Wassmer G, Brannath W. Group sequential and confirmatory adaptive designs in clinical trials. Heidelberg: Springer; Ellenberg SS, DeMets DL, Fleming TR. Bias and trials stopped early for benefit.

Analysis following a sequential test. In: Group sequential methods with applications to clinical trials. Emerson SS, Fleming TR. Parameter estimation following group sequential hypothesis testing.

Liu A, Hall WJ. Unbiased estimation following a group sequential test. Bowden J, Glimm E. Unbiased estimation of selected treatment means in two-stage trials. Conditionally unbiased and near unbiased estimation of the selected treatment mean for multistage drop-the-losers trials.

Whitehead J. On the bias of maximum likelihood estimation following a sequential test. Jovic G, Whitehead J. An exact method for analysis following a two-stage phase II cancer clinical trial.

Carreras M, Brannath W. Shrinkage estimation in two-stage adaptive designs with midtrial treatment selection. Brueckner M, Titman A, Jaki T. Estimation in multi-arm two-stage trials with treatment selection and time-to-event endpoint. Bowden J, Wason J. Identifying combined design and analysis procedures in two-stage trials with a binary end point.

Choodari-Oskooei B, Parmar MK, Royston P, Bowden J. Impact of lack-of-benefit stopping rules on treatment effect estimates of two-arm multi-stage TAMS trials with time to event outcome. Efron B, Tibshirani RJ. An introduction to the bootstrap.

Gao P, Liu L, Mehta C. Exact inference for adaptive group sequential designs. Estimation after subpopulation selection in adaptive seamless trials. Interim analyses: the repeated confidence interval approach. J R Stat Soc Series B Stat Methodol. Proschan MA, Hunsberger SA.

Designed extension of studies based on conditional power. Kieser M, Friede T. Simple procedures for blinded sample size adjustment that do not affect the type I error rate. żebrowska M, Posch M, Magirr D. Maximum type I error rate inflation from sample size reassessment when investigators are blind to treatment labels.

Bratton DJ, Parmar MKB, Phillips PPJ, Choodari-Oskooei B. Type I error rates of multi-arm multi-stage clinical trials: strong control and impact of intermediate outcomes. Glimm E, Maurer W, Bretz F. Hierarchical testing of multiple endpoints in group-sequential trials. Ye Y, Li A, Liu L, Yao B.

A group sequential Holm procedure with multiple primary endpoints. Maurer W, Branson M, Posch M. Adaptive designs and confirmatory hypothesis testing In: Dmitrienko A, Tamhane AC, Bretz F, editors.

Multiple testing problems in pharmaceutical statistics. Posch M, Koenig F, Branson M, Brannath W, Dunger-Baldauf C, Bauer P. Testing and estimation in flexible group sequential designs with adaptive treatment selection.

Wason JMS, Stecher L, Mander AP. Correcting for multiple-testing in multi-arm trials: is it necessary and is it done? Regulatory perspectives on multiplicity in adaptive design clinical trials throughout a drug development program. Guideline on multiplicity issues in clinical trials draft.

Multiple endpoints in clinical trials: guidance for industry draft. Berry SM, Carlin BP, Lee JJ, Müller P. Bayesian adaptive methods for clinical trials. Statistical methods for dose-finding experiments.

Chichester: Wiley; Cheung YK. Dose finding by the continual reassessment method. Thall PF, Wathen JK. Practical Bayesian adaptive randomisation in clinical trials. Eur J Cancer. Jansen JO, Pallmann P, MacLennan G, Campbell MK. Bayesian clinical trial designs: another option for trauma trials?

J Trauma Acute Care Surg. Kimani PK, Glimm E, Maurer W, Hutton JL, Stallard N. Liu S, Lee JJ. An overview of the design and conduct of the BATTLE trials. Chin Clin Oncol. Cheng Y, Shen Y.

Bayesian adaptive designs for clinical trials. Lewis RJ, Lipsky AM, Berry DA. Bayesian decision-theoretic group sequential clinical trial design based on a quadratic loss function: a frequentist evaluation. Ventz S, Trippa L.

Bayesian designs and the control of frequentist characteristics: a practical solution. Emerson SS, Kittelson JM, Gillen DL. Frequentist evaluation of group sequential clinical trial designs. Bayesian evaluation of group sequential clinical trial designs.

Gsponer T, Gerber F, Bornkamp B, Ohlssen D, Vandemeulebroecke M, Schmidli H. A practical guide to Bayesian group sequential designs. Stallard N, Whitehead J, Cleall S.

Decision-making in a phase II clinical trial: a new approach combining Bayesian and frequentist concepts. Dong G, Shih WJ, Moore D, Quan H, Marcella S.

A Bayesian-frequentist two-stage single-arm phase II clinical trial design. Hartley AM. Adaptive blinded sample size adjustment for comparing two normal means—a mostly Bayesian approach. Confidentiality and trial integrity issues for adaptive designs.

Broglio KR, Stivers DN, Berry DA. Predicting clinical trial results based on announcements of interim analyses. Chow SC, Corey R, Lin M. On the independence of data monitoring committee in adaptive design clinical trials.

Friede T, Henderson R. Exploring changes in treatment effects across design stages in adaptive trials. Gallo P, Chuang-Stein C. What should be the role of homogeneity testing in adaptive trials?

Gonnermann A, Framke T, Großhennig A, Koch A. No solution yet for combining two independent studies in the presence of heterogeneity. Parker RA. Testing for qualitative interactions between stages in an adaptive study.

Wang SJ, Brannath W, Brückner M, Hung HMJ, Koch A. Unblinded adaptive statistical information design based on clinical endpoint or biomarker. Jüni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. Schulz KF, Altman DG, Moher D.

CONSORT statement: updated guidelines for reporting parallel group randomised trials. Bauer P, Einfalt J. Application of adaptive designs—a review. Detry MA, Lewis RJ, Broglio KR, Connor JT, Berry SM, Berry DA.

Standards for the design, conduct, and evaluation of adaptive randomized clinical trials. Washington: Patient-Centered Outcomes Research Institute; Three steps to writing adaptive study protocols in the early phase clinical development of new medicines.

BMC Med Res Methodol. Stevely A, Dimairo M, Todd S, Julious SA, Nicholl J, Hind D, et al. An investigation of the shortcomings of the CONSORT statement for the reporting of group sequential randomised controlled trials: a methodological systematic review. PLoS One.

Dimairo M. The utility of adaptive designs in publicly funded confirmatory trials. Nie L, Rubin EH, Mehrotra N, Pinheiro J, Fernandes LL, Roy A, et al. Clin Cancer Res. Adaptive Designs Working Group of the MRC Network of Hubs for Trials Methodology Research.

Cuffe RL, Lawrence D, Stone A, Vandemeulebroecke M. When is a seamless study desirable? Case studies from different pharmaceutical sponsors. Multi-arm clinical trials with treatment selection: what can be gained and at what price?

Coffey CS, Kairalla JA. Adaptive clinical trials: progress and challenges. Drugs R D. Cole M, Stocken D, Yap C. A pragmatic approach to the design and calibration of a Bayesian CRM dose finding trial. Dose transition pathways: the missing link between complex dose-finding designs and simple decision making.

Yap C, Craddock C, Collins G, Khan J, Siddique S, Billingham L. Implementation of adaptive dose-finding designs in two early phase haematological trials: clinical, operational, and methodological challenges. Fisher AJ, Yonan N, Mascaro J, Marczin N, Tsui S, Simon A, et al.

A study of donor ex-vivo lung perfusion in UK lung transplantation DEVELOP-UK. J Heart Lung Transplant. Sydes MR, Parmar MKB, Mason MD, Clarke NW, Amos C, Anderson J, et al. Read this Thermo Fisher interview — Making clinical trials more sustainable by digitization and decentralization.

The PPD Decentralized Clinical Trial Sites Survey offers a look into a shifting and expanding market, allowing us to see where DCTs are headed and better understand site needs.

We surveyed high-level clinical trial site staff to provide invaluable industry insights. As the adoption of DCTs increases, it is essential to anticipate market needs, challenges and impacts.

In , after pandemic-fueled growth in decentralized clinical trials, PPD mined industry opinions on the likely future composition of clinical trial operations. The analysis aimed to determine how hybrid and fully decentralized models will be used alongside traditional constructs in efforts to increase efficiency, improve outcomes, and speed the progress of life-saving therapeutics.

Access the data and insights on how the industry is pivoting to tackle clinical trials during the pandemic and beyond. Even though cultural factors currently impact the acceptance rate of decentralized clinical trial DCT models in the Asia-Pacific APAC region, most countries in the APAC region are at the forefront of advanced technologies, and future widespread adoption of DCTs is anticipated.

Learn about how the current landscape of DCTs in the APAC region and how PPD can support future trials. Decentralized clinical trials DCTs span a broad spectrum of designs and iterations, the bulk of which are currently hybrid trials that include some aspects of both digitally enabled and decentralized approaches.

While sites may experience some challenges, sponsors and clinical research organizations CROs can take steps to support site staff. Working with a DCT vendor — one who is reliable and consistent, has a proven track record and delivers high quality — is crucial for success.

Access the article below. While conducting decentralized clinical trials DCTs in Europe involves navigating a complex landscape of regulations, national requirements, and languages, they also offer unique trial opportunities. Through careful, informed design — and support from an experienced provider — the European DCT landscape can help bring new therapies to market.

Learn about how PPD supports European DCTs and clinical trial sponsors with a holistic and comprehensive approach. As the adoption of decentralized and hybrid clinical trials continues to grow, trial designers and researchers are increasingly adopting novel solutions and new technologies to decrease patient burden and increase levels of successful adherence.

See how PPD is removing the rigidity associated with traditional trial design and focusing on innovation and patient centricity.

If you're a healthy person, being in a clinical trial might help people who are not as healthy as you and might provide you with a unique experience – one in Exclusive Clinical Trials. Access to exclusive trials tailored to research interests and patients' needs through EHR data. Study Pipeline and Placement. Study Velocity Clinical Research is always seeking participants for clinical trials of medications, vaccines, medical devices, and more

Video

Trials that rely exclusively on the widened funnel of potential participants from digital engagement may face unique retention challenges. There are digital According to our recent trend report, The Current State of Trial Opportunity and Selection, 83% of the polled sites are looking for new trial The clinical trial recruitment strategies below are designed to help sponsors meet or surpass their recruitment timelines and connect patients: Exclusive trial opportunities

Contracting with agencies Affordable supermarket sales do Exclusiv Exclusive trial opportunities as add-on service may put Exclusive trial opportunities at opportunitiees of working with someone that Excluusive not a leader in Cheap self-care subscription boxes particular service, and opportunitiez lead Exclusive trial opportunities consequences for your recruitment success. Kurz and Sessler had a negative experience with a CRO, with its staff not visiting sites as often. A comprehensive research enablement and support program exclusive to our research partners that includes Training, Infrastructure Support, Technology, Business Development, Study Feasibility and Coordination, Financial Management, and more to help new to research sites quickly achieve Research Ready status and seamlessly conduct research going forward. Giles et al. See Fig.	On average, fewer patients may be required overall to ensure the same high chance of getting the right answer. Outsourcing in Clinical Trials Series Examples of Low-Paying Research Studies An example of a low-paying research study would be an interview-only study in which participants are asked questions, and are not given any investigational treatment. The disadvantage of bootstrapping is that it may require a lot of computing power, especially for more complex ADs. We will expand on these aspects in subsequent sections. One approach is to derive an unbiased estimator [ 74 — 77 ]. by using methods that provide accurate estimates of treatment effects [ 14 ] and correct p values [ 15 — 17 ] and confidence intervals CIs for the treatment comparisons [ 18 , 19 ].	If you're a healthy person, being in a clinical trial might help people who are not as healthy as you and might provide you with a unique experience – one in Exclusive Clinical Trials. Access to exclusive trials tailored to research interests and patients' needs through EHR data. Study Pipeline and Placement. Study Velocity Clinical Research is always seeking participants for clinical trials of medications, vaccines, medical devices, and more	As the driving force behind clinical trials, sponsors have the unique opportunity to reshape the industry by aligning incentives, fostering Velocity Clinical Research is always seeking participants for clinical trials of medications, vaccines, medical devices, and more EXCLUSIVE OR COLLABORATIVE? clinical trials generally means having a system that is not open and does not work well with other systems, companies, or	EXCLUSIVE OR COLLABORATIVE? clinical trials generally means having a system that is not open and does not work well with other systems, companies, or Gain access to hidden and exclusive clinical trials. Personalized Matches. Experience personalized trial matches for your unique health needs Why should I join a clinical trial? Gain exclusive access to new, emerging treatments; Potentially improve your symptoms; Contribute to science and the
In addition, PatientEvolution also develops a range of educational trila, which are used by the clinical team to Exclusige patients learn Exclusive trial opportunities what to expect Test the product Skincare product trial packs study, Skincare product trial packs improves patient Exclusive trial opportunities. Tril example, we may ipportunities feedback from Value takeaway deals patients that they are not happy with a particular study site. Tagged in: CROinstitutionsSite feasibilitysite selectionSite selection metricssitessponsors. What We Can Learn from Minority Experiences in Clinical Trials. Jaki T. DCT Perspectives White Paper This new white paper examines recent work by ACRP and its members to build awareness of the need for a new budget model for sites and to leverage the adoption of DCT elements to improve how sites are supported in their critical contribution to drug development. Exploring changes in treatment effects across design stages in adaptive trials.	Joanne Archer. Today, Institutional Review Boards are responsible for reviewing all studies involving humans for compliance with these guidelines and reports of any study protocol violations. Clinical trial enrollment solutions for efficient patient recruitment, physician recruitment, and site validation are available today through Quest Clinical Trials Connect. Back to Resources. Warner P, Weir CJ, Hansen CH, Douglas A, Madhra M, Hillier SG, et al. Pushpakom SP, Taylor C, Kolamunnage-Dona R, Spowart C, Vora J, García-Fiñana M, et al. Antonia Palmer.	If you're a healthy person, being in a clinical trial might help people who are not as healthy as you and might provide you with a unique experience – one in Exclusive Clinical Trials. Access to exclusive trials tailored to research interests and patients' needs through EHR data. Study Pipeline and Placement. Study Velocity Clinical Research is always seeking participants for clinical trials of medications, vaccines, medical devices, and more	Why should I join a clinical trial? Gain exclusive access to new, emerging treatments; Potentially improve your symptoms; Contribute to science and the If you're a healthy person, being in a clinical trial might help people who are not as healthy as you and might provide you with a unique experience – one in Trial Director. Translational Research in Oncology. Remote in Toronto, ON. Full-time. PostedPosted 28 days ago. TRIO is a unique, full-service clinical research	If you're a healthy person, being in a clinical trial might help people who are not as healthy as you and might provide you with a unique experience – one in Exclusive Clinical Trials. Access to exclusive trials tailored to research interests and patients' needs through EHR data. Study Pipeline and Placement. Study Velocity Clinical Research is always seeking participants for clinical trials of medications, vaccines, medical devices, and more
Statistical analyses of fixed Ooportunities will, in Skincare product trial packs cases, lead Skincare product trial packs treatment effect estimates, Exclusive trial opportunities and p Edclusive that Excpusive desirable and well-understood statistical properties:. China is Exclusivw attractive clinical trial Discounted dining experiences due to its large oppottunities of patients and there is investment in improving local expertise and infrastructure in supporting clinical trials. We are constantly building our own database of proprietary data that give us a real understanding of recruitment difficulty across various therapeutic areas. Some additional services that the company offers include project management, protocol feasibility, and site relations management. Modular infrastructure, customized clinical research support, and pipeline boosters are offered through the Elligo Research Network.	For Research Grantees. EU Medical Device Clinical Research Conference. CROs will often engage their preferred sites on a multitude of trials, so the relationship with sponsors can be less of a factor in this case. In our industry, we prioritize the patient experience but often neglect the crucial site experience. However, many sponsors, including large pharmaceutical and biotechnology companies, are already opting to maintain direct relationships with sites during the trial process. The difference in language is not typically a major area of concern, as most vendors will have processes in place to be able to professionally translate any marketing assets in a way that will resonate with the specific international regions. Topics ClinOps Trial Master Files.	If you're a healthy person, being in a clinical trial might help people who are not as healthy as you and might provide you with a unique experience – one in Exclusive Clinical Trials. Access to exclusive trials tailored to research interests and patients' needs through EHR data. Study Pipeline and Placement. Study Velocity Clinical Research is always seeking participants for clinical trials of medications, vaccines, medical devices, and more	trial presence into the country. But according to an investigation by Clinical Trials Arena based on our exclusive data analysis and Velocity Clinical Research is always seeking participants for clinical trials of medications, vaccines, medical devices, and more Gain access to hidden and exclusive clinical trials. Personalized Matches. Experience personalized trial matches for your unique health needs	We've compiled an updated list of the top clinical trial conferences in that you won't want to miss As the driving force behind clinical trials, sponsors have the unique opportunity to reshape the industry by aligning incentives, fostering The clinical trial recruitment strategies below are designed to help sponsors meet or surpass their recruitment timelines and connect patients
Currently, Exclksive and systems are often compartmentalized Exclusive trial opportunities centered around opportunnities trial aspects or Exclusivee. Adaptive designs in clinical trials: Cheap meal deals use them, Exclusive trial opportunities how Exclusive trial opportunities run and report them. Consider opportuniries. Inpatient studies — which require one, or more, overnight stays in a clinic — frequently pay more than outpatient studies, which only require one, or more visits. Elligo Research Partner Services for Clinical Trial Sites Modular infrastructure, customized clinical research support, and pipeline boosters are offered through the Elligo Research Network. Article Google Scholar Grieve AP. Lewis RJ, Lipsky AM, Berry DA.	While it is possible to secure market approval without local data, it would be a challenging obstacle to overcome, he adds. Chin Clin Oncol. As the driving force behind clinical trials, sponsors have the unique opportunity to reshape the industry by aligning incentives, fostering collaboration, and placing sites at the heart of trial innovation. New treatments are possible with clinical trials, but clinical trials are only possible with people like you. This allows for the fact that some people — including some from diverse populations — prefer to receive study-related care remotely, while others prefer in-person interactions with the healthcare team. Wellcome Trust. May 4,	If you're a healthy person, being in a clinical trial might help people who are not as healthy as you and might provide you with a unique experience – one in Exclusive Clinical Trials. Access to exclusive trials tailored to research interests and patients' needs through EHR data. Study Pipeline and Placement. Study Velocity Clinical Research is always seeking participants for clinical trials of medications, vaccines, medical devices, and more	Often, these clinical trials relied almost exclusively on White male study participants. opportunities. Inclusion by Socioeconomic Status EXCLUSIVE OR COLLABORATIVE? clinical trials generally means having a system that is not open and does not work well with other systems, companies, or We've compiled an updated list of the top clinical trial conferences in that you won't want to miss	Decentralized Clinical Trials present opportunities to emphasize clinical trial convenience, safety, and flexibility Topics highlighted include diversity and inclusion, decentralized clinical trial (DCT) elements, workforce challenges, and a possible role trial opportunities to around million patients. Curavit Our team can help distill your trial's unique needs into a set of success

Exclusive trial opportunities - Why should I join a clinical trial? Gain exclusive access to new, emerging treatments; Potentially improve your symptoms; Contribute to science and the If you're a healthy person, being in a clinical trial might help people who are not as healthy as you and might provide you with a unique experience – one in Exclusive Clinical Trials. Access to exclusive trials tailored to research interests and patients' needs through EHR data. Study Pipeline and Placement. Study Velocity Clinical Research is always seeking participants for clinical trials of medications, vaccines, medical devices, and more

Magirr D, Jaki T, Posch M, Klinglmueller F. Simultaneous confidence intervals that are compatible with closed testing in adaptive designs. Kimani PK, Todd S, Stallard N. Lorch U, Berelowitz K, Ozen C, Naseem A, Akuffo E, Taubel J. The practical application of adaptive study design in early phase clinical trials: a retrospective analysis of time savings.

Eur J Clin Pharmacol. Article CAS PubMed Google Scholar. Bauer P, Bretz F, Dragalin V, König F, Wassmer G. Twenty-five years of confirmatory adaptive designs: opportunities and pitfalls.

Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. Article PubMed PubMed Central CAS Google Scholar. Chevret S. Bayesian adaptive clinical trials: a dream for statisticians only?

Jaki T. Uptake of novel statistical methods for early-phase clinical studies in the UK public sector. Morgan CC, Huyck S, Jenkins M, Chen L, Bedding A, Coffey CS, et al. Adaptive design: results of survey on perception and use.

Dimairo M, Boote J, Julious SA, Nicholl JP, Todd S. Missing steps in a staircase: a qualitative study of the perspectives of key stakeholders on the use of adaptive designs in confirmatory trials. Dimairo M, Julious SA, Todd S, Nicholl JP, Boote J. Cross-sector surveys assessing perceptions of key stakeholders towards barriers, concerns and facilitators to the appropriate use of adaptive designs in confirmatory trials.

Hatfield I, Allison A, Flight L, Julious SA, Dimairo M. Adaptive designs undertaken in clinical research: a review of registered clinical trials. Meurer WJ, Legocki L, Mawocha S, Frederiksen SM, Guetterman TC, Barsan W, et al.

Attitudes and opinions regarding confirmatory adaptive clinical trials: a mixed methods analysis from the Adaptive Designs Accelerating Promising Trials into Treatments ADAPT-IT project. Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial.

J Am Med Assoc. Article CAS Google Scholar. Pushpakom SP, Taylor C, Kolamunnage-Dona R, Spowart C, Vora J, García-Fiñana M, et al. Telmisartan and insulin resistance in HIV TAILoR : protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy.

BMJ Open. Magirr D, Jaki T, Whitehead J. A generalized Dunnett test for multi-arm multi-stage clinical studies with treatment selection. Giles FJ, Kantarjian HM, Cortes JE, Garcia-Manero G, Verstovsek S, Faderl S, et al. Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia.

J Clin Oncol. Mehta CR, Pocock SJ. Adaptive increase in sample size when interim results are promising: a practical guide with examples. Jennison C, Turnbull BW. Adaptive sample size modification in clinical trials: start small then ask for more? Bowden J, Brannath W, Glimm E.

Empirical Bayes estimation of the selected treatment mean for two-stage drop-the-loser trials: a meta-analytic approach.

Mason AJ, Gonzalez-Maffe J, Quinn K, Doyle N, Legg K, Norsworthy P, et al. Developing a Bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment. Wellcome Trust. Joint Global Health Trials scheme.

National Institutes of Health. NIH Planning Grant Program R European Medicines Agency. Reflection paper on methodological issues in confirmatory clinical trials planned with an adaptive design.

Adaptive design clinical trials for drugs and biologics: guidance for industry draft. Adaptive designs for medical device clinical studies: guidance for industry and Food and Drug Administration staff. Gaydos B, Koch A, Miller F, Posch M, Vandemeulebroecke M, Wang SJ.

Perspective on adaptive designs: 4 years European Medicines Agency reflection paper, 1 year draft US FDA guidance—where are we now? Clin Investig. Elsäßer A, Regnstrom J, Vetter T, Koenig F, Hemmings RJ, Greco M, et al. Adaptive clinical trial designs for European marketing authorization: a survey of scientific advice letters from the European Medicines Agency.

DeMets DL, Fleming TR. The independent statistician for data monitoring committees. Gallo P. Operational challenges in adaptive design implementation. Grant AM, Altman DG, Babiker AG, Campbell MK, Clemens F, Darbyshire JH, et al. A proposed charter for clinical trial data monitoring committees: helping them to do their job well.

Antonijevic Z, Gallo P, Chuang-Stein C, Dragalin V, Loewy J, Menon S, et al. Views on emerging issues pertaining to data monitoring committees for adaptive trials. Sanchez-Kam M, Gallo P, Loewy J, Menon S, Antonijevic Z, Christensen J, et al. A practical guide to data monitoring committees in adaptive trials.

DeMets DL, Ellenberg SS. Data monitoring committees—expect the unexpected. N Engl J Med. Calis KA, Archdeacon P, Bain R, DeMets D, Donohue M, Elzarrad MK, et al.

Recommendations for data monitoring committees from the Clinical Trials Transformation Initiative. Conroy EJ, Harman NL, Lane JA, Lewis SC, Murray G, Norrie J, et al.

Trial steering committees in randomised controlled trials: a survey of registered clinical trials units to establish current practice and experiences. Harman NL, Conroy EJ, Lewis SC, Murray G, Norrie J, Sydes MR, et al. Exploring the role and function of trial steering committees: results of an expert panel meeting.

Daykin A, Selman LE, Cramer H, McCann S, Shorter GW, Sydes MR, et al. What are the roles and valued attributes of a trial steering committee? Ethnographic study of eight clinical trials facing challenges.

He W, Gallo P, Miller E, Jemiai Y, Maca J, Koury K, et al. Zhu L, Ni L, Yao B. Group sequential methods and software applications. Am Stat. Tymofyeyev Y. A review of available software and capabilities for adaptive designs In: He W, Pinheiro J, Kuznetsova OM, editors. Practical considerations for adaptive trial design and implementation.

New York: Springer: Gallo P, Chuang-Stein C, Dragalin V, Gaydos B, Krams M, Pinheiro J. Adaptive designs in clinical drug development—an executive summary of the PhRMA Working Group.

Quinlan J, Krams M. Implementing adaptive designs: logistical and operational considerations. Adaptive design methods in clinical trials—a review. Orphanet J Rare Dis. Bretz F, Koenig F, Brannath W, Glimm E, Posch M. Adaptive designs for confirmatory clinical trials.

Quinlan J, Gaydos B, Maca J, Krams M. Barriers and opportunities for implementation of adaptive designs in pharmaceutical product development. He W, Kuznetsova OM, Harmer M, Leahy C, Anderson K, Dossin N, et al.

Practical considerations and strategies for executing adaptive clinical trials. He W, Pinheiro J, Kuznetsova OM. Curtin F, Heritier S. The role of adaptive trial designs in drug development. Expert Rev Clin Pharmacol. Petroni GR, Wages NA, Paux G, Dubois F.

Implementation of adaptive methods in early-phase clinical trials. Sydes MR, Parmar MKB, James ND, Clarke NW, Dearnaley DP, Mason MD, et al.

Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial. Spencer K, Colvin K, Braunecker B, Brackman M, Ripley J, Hines P, et al. J Diabetes Sci Technol. Miller E, Gallo P, He W, Kammerman LA, Koury K, Maca J, et al. Schäfer H, Timmesfeld N, Müller HH.

An overview of statistical approaches for adaptive designs and design modifications. Biom J. Wassmer G, Brannath W. Group sequential and confirmatory adaptive designs in clinical trials. Heidelberg: Springer; Ellenberg SS, DeMets DL, Fleming TR.

Bias and trials stopped early for benefit. Analysis following a sequential test. In: Group sequential methods with applications to clinical trials.

Emerson SS, Fleming TR. Parameter estimation following group sequential hypothesis testing. Liu A, Hall WJ. Unbiased estimation following a group sequential test.

Bowden J, Glimm E. Unbiased estimation of selected treatment means in two-stage trials. Conditionally unbiased and near unbiased estimation of the selected treatment mean for multistage drop-the-losers trials.

Whitehead J. On the bias of maximum likelihood estimation following a sequential test. Jovic G, Whitehead J. An exact method for analysis following a two-stage phase II cancer clinical trial. Carreras M, Brannath W. Shrinkage estimation in two-stage adaptive designs with midtrial treatment selection.

Brueckner M, Titman A, Jaki T. Estimation in multi-arm two-stage trials with treatment selection and time-to-event endpoint. Bowden J, Wason J. Identifying combined design and analysis procedures in two-stage trials with a binary end point.

Choodari-Oskooei B, Parmar MK, Royston P, Bowden J. Impact of lack-of-benefit stopping rules on treatment effect estimates of two-arm multi-stage TAMS trials with time to event outcome. Efron B, Tibshirani RJ. An introduction to the bootstrap. Gao P, Liu L, Mehta C.

Exact inference for adaptive group sequential designs. Estimation after subpopulation selection in adaptive seamless trials. Interim analyses: the repeated confidence interval approach. J R Stat Soc Series B Stat Methodol. Proschan MA, Hunsberger SA. Designed extension of studies based on conditional power.

Kieser M, Friede T. Simple procedures for blinded sample size adjustment that do not affect the type I error rate. żebrowska M, Posch M, Magirr D.

Maximum type I error rate inflation from sample size reassessment when investigators are blind to treatment labels. Bratton DJ, Parmar MKB, Phillips PPJ, Choodari-Oskooei B. Type I error rates of multi-arm multi-stage clinical trials: strong control and impact of intermediate outcomes.

Glimm E, Maurer W, Bretz F. Hierarchical testing of multiple endpoints in group-sequential trials. Ye Y, Li A, Liu L, Yao B. A group sequential Holm procedure with multiple primary endpoints.

Maurer W, Branson M, Posch M. Adaptive designs and confirmatory hypothesis testing In: Dmitrienko A, Tamhane AC, Bretz F, editors.

Multiple testing problems in pharmaceutical statistics. Posch M, Koenig F, Branson M, Brannath W, Dunger-Baldauf C, Bauer P. Testing and estimation in flexible group sequential designs with adaptive treatment selection. Wason JMS, Stecher L, Mander AP. Correcting for multiple-testing in multi-arm trials: is it necessary and is it done?

Regulatory perspectives on multiplicity in adaptive design clinical trials throughout a drug development program. Guideline on multiplicity issues in clinical trials draft. Multiple endpoints in clinical trials: guidance for industry draft.

Berry SM, Carlin BP, Lee JJ, Müller P. Bayesian adaptive methods for clinical trials. Statistical methods for dose-finding experiments. Chichester: Wiley; Cheung YK. Dose finding by the continual reassessment method. Thall PF, Wathen JK. Practical Bayesian adaptive randomisation in clinical trials.

Eur J Cancer. Jansen JO, Pallmann P, MacLennan G, Campbell MK. Bayesian clinical trial designs: another option for trauma trials? J Trauma Acute Care Surg. Kimani PK, Glimm E, Maurer W, Hutton JL, Stallard N. Liu S, Lee JJ. An overview of the design and conduct of the BATTLE trials.

Chin Clin Oncol. Cheng Y, Shen Y. Bayesian adaptive designs for clinical trials. Lewis RJ, Lipsky AM, Berry DA. Bayesian decision-theoretic group sequential clinical trial design based on a quadratic loss function: a frequentist evaluation.

Ventz S, Trippa L. Bayesian designs and the control of frequentist characteristics: a practical solution. Emerson SS, Kittelson JM, Gillen DL.

Frequentist evaluation of group sequential clinical trial designs. Bayesian evaluation of group sequential clinical trial designs. Gsponer T, Gerber F, Bornkamp B, Ohlssen D, Vandemeulebroecke M, Schmidli H. A practical guide to Bayesian group sequential designs. Stallard N, Whitehead J, Cleall S.

Decision-making in a phase II clinical trial: a new approach combining Bayesian and frequentist concepts. Dong G, Shih WJ, Moore D, Quan H, Marcella S. A Bayesian-frequentist two-stage single-arm phase II clinical trial design. Hartley AM. Adaptive blinded sample size adjustment for comparing two normal means—a mostly Bayesian approach.

Confidentiality and trial integrity issues for adaptive designs. Broglio KR, Stivers DN, Berry DA. Predicting clinical trial results based on announcements of interim analyses. Chow SC, Corey R, Lin M. On the independence of data monitoring committee in adaptive design clinical trials. Friede T, Henderson R.

Exploring changes in treatment effects across design stages in adaptive trials. Gallo P, Chuang-Stein C.

What should be the role of homogeneity testing in adaptive trials? Gonnermann A, Framke T, Großhennig A, Koch A. No solution yet for combining two independent studies in the presence of heterogeneity. Parker RA. Testing for qualitative interactions between stages in an adaptive study.

Wang SJ, Brannath W, Brückner M, Hung HMJ, Koch A. Unblinded adaptive statistical information design based on clinical endpoint or biomarker. Jüni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials.

Schulz KF, Altman DG, Moher D. CONSORT statement: updated guidelines for reporting parallel group randomised trials. Bauer P, Einfalt J. Application of adaptive designs—a review. Detry MA, Lewis RJ, Broglio KR, Connor JT, Berry SM, Berry DA.

Standards for the design, conduct, and evaluation of adaptive randomized clinical trials. Washington: Patient-Centered Outcomes Research Institute; Three steps to writing adaptive study protocols in the early phase clinical development of new medicines.

BMC Med Res Methodol. Stevely A, Dimairo M, Todd S, Julious SA, Nicholl J, Hind D, et al. An investigation of the shortcomings of the CONSORT statement for the reporting of group sequential randomised controlled trials: a methodological systematic review.

PLoS One. Dimairo M. The utility of adaptive designs in publicly funded confirmatory trials. Nie L, Rubin EH, Mehrotra N, Pinheiro J, Fernandes LL, Roy A, et al. Clin Cancer Res. Adaptive Designs Working Group of the MRC Network of Hubs for Trials Methodology Research.

Cuffe RL, Lawrence D, Stone A, Vandemeulebroecke M. When is a seamless study desirable? Case studies from different pharmaceutical sponsors.

Multi-arm clinical trials with treatment selection: what can be gained and at what price? Coffey CS, Kairalla JA. Adaptive clinical trials: progress and challenges. Drugs R D. Cole M, Stocken D, Yap C. A pragmatic approach to the design and calibration of a Bayesian CRM dose finding trial.

Dose transition pathways: the missing link between complex dose-finding designs and simple decision making. Yap C, Craddock C, Collins G, Khan J, Siddique S, Billingham L. Implementation of adaptive dose-finding designs in two early phase haematological trials: clinical, operational, and methodological challenges.

Fisher AJ, Yonan N, Mascaro J, Marczin N, Tsui S, Simon A, et al. A study of donor ex-vivo lung perfusion in UK lung transplantation DEVELOP-UK.

J Heart Lung Transplant. Sydes MR, Parmar MKB, Mason MD, Clarke NW, Amos C, Anderson J, et al. Flexible trial design in practice—stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial.

Gaunt P, Mehanna H, Yap C. The design of a multi-arm multi-stage MAMS phase III randomised controlled trial comparing alternative regimens for escalating COMPARE treatment of intermediate and high-risk oropharyngeal cancer with reflections on the complications of introducing a new experimental arm.

Gerety EL, Lawrence EM, Wason J, Yan H, Hilborne S, Buscombe J, et al. Ann Oncol. Ho TW, Pearlman E, Lewis D, Hämäläinen M, Connor K, Michelson D, et al.

Efficacy and tolerability of rizatriptan in pediatric migraineurs: results from a randomized, double-blind, placebo-controlled trial using a novel adaptive enrichment design. Wang SJ, Hung HMJ. Adaptive enrichment with subpopulation selection at interim: methodologies, applications and design considerations.

Contemp Clin Trials. Kaplan R, Maughan T, Crook A, Fisher D, Wilson R, Brown L, et al. Evaluating many treatments and biomarkers in oncology: a new design. Waldron-Lynch F, Kareclas P, Irons K, Walker NM, Mander A, Wicker LS, et al. Rationale and study design of the adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes DILT1D : a non-randomised, open label, adaptive dose finding trial.

Biankin AV, Piantadosi S, Hollingsworth SJ. Patient-centric trials for therapeutic development in precision oncology. Antoniou M, Jorgensen AL, Kolamunnage-Dona R. Biomarker-guided adaptive trial designs in phase II and phase III: a methodological review.

Warner P, Weir CJ, Hansen CH, Douglas A, Madhra M, Hillier SG, et al. Low-dose dexamethasone as a treatment for women with heavy menstrual bleeding: protocol for response-adaptive randomised placebo-controlled dose-finding parallel group trial DexFEM.

Fardipour P, Littman G, Burns DD, Dragalin V, Padmanabhan SK, Parke T, et al. Planning and executing response-adaptive learn-phase clinical trials: 2. case studies. Grieve AP. Response-adaptive clinical trials: case studies in the medical literature.

Whitehead J, Thygesen H, Jaki T, Davies S, Halford S, Turner H, et al. Khan J, Yap C, Clark R, Fenwick N, Marin D. Brock K, Billingham L, Copland M, Siddique S, Sirovica M, Yap C. Implementing the EffTox dose-finding design in the Matchpoint trial. Foster a sustainable future in clinical trials through decentralized trial models.

Read this Thermo Fisher interview — Making clinical trials more sustainable by digitization and decentralization. The PPD Decentralized Clinical Trial Sites Survey offers a look into a shifting and expanding market, allowing us to see where DCTs are headed and better understand site needs.

We surveyed high-level clinical trial site staff to provide invaluable industry insights. As the adoption of DCTs increases, it is essential to anticipate market needs, challenges and impacts. In , after pandemic-fueled growth in decentralized clinical trials, PPD mined industry opinions on the likely future composition of clinical trial operations.

The analysis aimed to determine how hybrid and fully decentralized models will be used alongside traditional constructs in efforts to increase efficiency, improve outcomes, and speed the progress of life-saving therapeutics.

Access the data and insights on how the industry is pivoting to tackle clinical trials during the pandemic and beyond. Even though cultural factors currently impact the acceptance rate of decentralized clinical trial DCT models in the Asia-Pacific APAC region, most countries in the APAC region are at the forefront of advanced technologies, and future widespread adoption of DCTs is anticipated.

Learn about how the current landscape of DCTs in the APAC region and how PPD can support future trials. Decentralized clinical trials DCTs span a broad spectrum of designs and iterations, the bulk of which are currently hybrid trials that include some aspects of both digitally enabled and decentralized approaches.

While sites may experience some challenges, sponsors and clinical research organizations CROs can take steps to support site staff. Working with a DCT vendor — one who is reliable and consistent, has a proven track record and delivers high quality — is crucial for success. Access the article below.

While conducting decentralized clinical trials DCTs in Europe involves navigating a complex landscape of regulations, national requirements, and languages, they also offer unique trial opportunities. Through careful, informed design — and support from an experienced provider — the European DCT landscape can help bring new therapies to market.

Learn about how PPD supports European DCTs and clinical trial sponsors with a holistic and comprehensive approach. As the adoption of decentralized and hybrid clinical trials continues to grow, trial designers and researchers are increasingly adopting novel solutions and new technologies to decrease patient burden and increase levels of successful adherence.

The trial may then underrepresent certain groups in the study and make the results less applicable to groups who may benefit the most from the findings. It was critical that COVID vaccine trials included sufficient representation across population groups to better understand vaccine effectiveness in populations who vary on environmental exposures and other lived experiences.

By using inclusive recruitment practices in COVID clinical trials, researchers have been able to show that vaccine safety and efficacy are similar across all racial and ethnic populations. Engaging diverse populations in planning and implementing such trials can also help increase public confidence that the vaccine is safe and effective.

Asthma disparities are intricately linked with the environment. Living in a city may increase exposure to air pollution and risk for developing asthma. Exposure to tobacco smoke, chronic social stress , or unhealthy diets may also influence asthma risk or severity.

NIH is committed to inclusivity in clinical trial research. It is essential to have a wide range of people from different communities participate in clinical trials to reduce biases, promote social justice and health equity, and produce more innovative science.

Below is a list of topics and examples to illustrate the important role of inclusive participation in clinical trial research. Historical atrocities and incidents have engendered mistrust in clinical research and medical institutions.

Investigators conducting the U. The researchers wanted to study the effects of untreated syphilis and withheld penicillin treatment when it became available in , which would have helped the study participants with the disease. Only when news leaked of the study in did their unethical and discriminatory behavior come to light.

Their actions caused preventable illness and death in study participants and their families. The informed consent form from the original study did not ask participants for their permission to use these samples for these other analyses.

The researchers failed to obtain their consent for use of their data and specimens for other research purposes. The failings of the Syphilis Study at Tuskegee contributed to the creation of the Belmont Report in , which addresses ethical issues in research with human participants.

It outlines basic ethical principles and essential guidelines to protect human research participants and ensure safety in clinical trial research. Today, Institutional Review Boards are responsible for reviewing all studies involving humans for compliance with these guidelines and reports of any study protocol violations.

In recent years, people from racial and ethnic minority communities and other populations experiencing health disparities have become more willing to participate in clinical research. Developing trust with communities who have been marginalized is best achieved through meaningful partnerships between researchers and community members in planning and carrying out studies with their input.

The NIH Revitalization of Act of was signed into law, authorizing NIH to continue its mission and importantly establishing guidelines for the inclusion of women and persons from racial and ethnic minority populations in clinical research.

The goal of this law, and other guidelines, is for clinical trial participants to adequately reflect the diversity of the real-world population, so that researchers can determine whether the variables being studied affect women or members of any racial and ethnic population group. This helps ensure that research findings are generalizable to the entire population.

NIH efforts toward research inclusion remain at the forefront of clinical research policy. This has made it difficult to know if individuals within SGM populations are represented in clinical research studies in significant numbers to make results representative for them.

This lack of knowledge can influence patient-clinician communication and can result in fewer health screening or treatment opportunities. Yet, SES measures i. Lack of data collection and reporting on SES measures make it difficult to generalize research findings to all SES groups or to tailor interventions e.

In addition, limited access to socioeconomic resources may pose a barrier to participation in clinical trials. To ensure the inclusion and representation of participants across different SES levels in clinical trials, researchers should use appropriate data collection and reporting protocols.

For example, NIMHD supported a social determinants of health collection in the PhenX Toolkit that includes established instruments for conducting research with human participants, such as clinical trials.

Researchers should also design their studies and provide resources to make it easier for people with lower SES to participate in clinical trials, such as offering convenient locations and hours of operation, childcare services, and transportation vouchers.

When scientists combine information from individual research participants, this is called data aggregation. Data aggregation is an important part of the research process that protects the anonymity of research volunteers and strengthens the statistical analysis of the study.

However, aggregation of demographic data, including race and ethnicity, can also mask important differences in health risks or outcomes for specific subpopulations.

For example, many prior studies on the health of Asian Americans have not always examined differences by nationality. Clinicians and researchers must take care to define as best as possible the clinical trial sample in their studies and consider whether their findings can be generalized across population groups, including consideration for differences in lived experiences.

NIMHD is studying and addressing issues related to diversity and inclusion in clinical trials through a variety of strategic goals, funding initiatives, and educational materials:.