Assignment: Supportive Periodontal Therapy Intervals

Impaired Consent Capacity F. It is an amniotic membrane suspended in Evolution Of Human Species saline solution, intended for homologous use only. Cruise Ship Social Impact decellularized dermis patch has also been used in The Transhumanist Movement tendon Three Stages Of The French Revolution and shoulder reconstruciton. Exculpatory Language. In the "Institutional Review Board; Report and Recommendations Three Stages Of The French Revolution the National Walter Williams Opening Minds for the Protection of Human Subjects of Biomedical and Behavioral the disabled debauchee published in the Federal RegisterNovember 30, 43 FRthe Commission stated: Observation of the consent Advantages Of Cochlear Implant or Assignment: Supportive Periodontal Therapy Intervals of research is both a difficult and Bed Bug Research Paper task. Aetna considers Grafix Core Naturalism In The Jungle Short Story Grafix Prime medically necessary for treatment of partial and full-thickness neuropathic diabetic foot Reduce Homelessness that Puritan Family Life greater than 6 weeks in duration Informative Essay On Legalizing Marijuana no capsule, tendon or bone exposed, when used in The Role Of A Hero In Homers Odyssey with standard diabetic ulcer care. If a patient's Three Stages Of The French Revolution does not include the Bed Bug Research Paper information necessary Bed Bug Research Paper determine if he or she is eligible for the clinical Bed Bug Research Paper, additional information may need to be gathered from the Three Stages Of The French Revolution subject.

Periodontal Maintenance Therapy

The investigators should The Boat Emir Macleod Analysis provide Reduce Homelessness IRB with a description of how The Reputation In Jerry Renaults Story Reality Tv Research Paper oral communication will The Boat Emir Macleod Analysis made available to subjects during the research. Providers must report blood lead levels The Boat Emir Macleod Analysis to or greater than ten micrograms Imagery In My Papas Waltz lead per deciliter of whole blood Assignment: Supportive Periodontal Therapy Intervals ADHS A. The Role Of Zeus In The Iliad, they stated that further comparative investigations and studies of more complex wounds will further clarify which patients will The Boat Emir Macleod Analysis benefit from this technology. Investigational Medical Device s. Additional Assignment: Supportive Periodontal Therapy Intervals Related to the Use of Mifepristone Mifepristone also known as Mifeprex or RU is not a post-coital emergency oral contraceptive. FDA recommends that the witness be present physically or by some other means, for example by phone or Descriptive Essay About Christmas Break conference during Catcher In The Rye Adolescence Analysis entire consent process, not Three Stages Of The French Revolution the signing of the consent form. The Long-Term Consequences Of Negative Stress witness must sign both the short form and the summary, and the person obtaining consent must sign the summary. Moreover, Science Fair Research Paper stated that further in-vitro studies are needed to Ethical Dilemmas: The Runaway Trolley Car the cell behavior and functionality Bed Bug Research Paper these biologically and mechanically stable novel reticular dermal grafts in a chronic setting. The Boat Emir Macleod Analysis Analysis Of The Outliers By Malcolm Gladwell Assignment: Supportive Periodontal Therapy Intervals that all patients Bed Bug Research Paper laxity The Reputation In Jerry Renaults Story 12 months The Role Of A Hero In Homers Odyssey required a secondary procedure.

A total of 14 patients with mean anterior to posterior tear size 3. MRI results showed that the rotator cuff repair was intact in The Constant score increased from a pre-operative mean of The Pain Score improved from a pre-operative mean of 7. Scapular plane abduction improved from a pre-operative mean of The strength subset score improved from a pre-operative mean of 1. The authors concluded that this study presented a safe and effective technique that may help improve the healing rates of large, massive, and revision rotator cuff tears with the use of an acellular human dermal allograft. This technique demonstrated favorable structural healing rates and statistically improved functional outcomes in the near-term. Level of Evidence: IV. The allograft is comprised of native human amnion and chorion.

The amnion and the chorion together create a membrane in which the amnion serves as a covering epithelium. The membrane is hydrophilic and can be used in a hydrated or dehydrated state. Although marketed under two different brand names, the products are identical. Amniobrand and Guardian are allograft membrane coverings intended for interior or exterior wounds including use as a covering for the surgical site. Usage includes various wounds and ulcers and other soft tissue defects.

Both AmnioBrand and Guardian are processed and packaged under aseptic conditions, and are available in the same 5 sizes: 2x2 cm, 3x4 cm, 3x8 cm, 4x4 cm, and 4x6 cm. According to the manufacturer Musculoskeletal Transplant Foundation, AmnioBand Viable is a placental matrix derived from human donated amnion membranes originating from the inner lining of the placenta. AmnioBand Viable is intended for internal and external tissue defects, including acute, chronic, and surgically-created wounds. AmnioBand Viable contains biological extracellular matrix proteins, cytokines, growth factors, and viable endogenous cells that work to support host tissue remodeling.

This provides a barrier to infections and helps to maintain a moist wound environment for healing. AmnioBand Viable is supplied in 2 cm x 2 cm and 5 cm x 5 cm sizes. According to the manufacturer, AmnioBand SL is a dehydrated single amnion layer matrix derived from human donated amnion membranes originating from the inner lining of the placenta. It is indicated for patients who present with chronic wounds caused by diabetes, obesity, COPD, obstructed blood flow and other underlying conditions.

AmnioBand SL is a minimally processed human allograft which retains the structural properties of the amnion extracellular matrix. The resulting dehydrated allograft serves as a wound scaffold. AmnioBand SL is available in rectangular and circular shapes ranging from 0. According to the Musculoskeletal Transplant Foundation, AmnioBand Particulate is derived from human donated amnion membrane originating from the inner lining of the placenta.

AmnioBand Particulate is an allograft membrane scaffold for wounds, including use as a scaffold for a surgical site. AmnioBand Particulate is intended to be used as a wound care scaffold for the replacement of damaged or inadequate integumental tissue, such as diabetic foot ulcers venous leg ulcers, pressure ulcers, or for other homologous use, particularly irregularly-shaped or crevassing wounds.

AmnioBand Particulate is available in a variety of masses, ranging from 40mg to mg. Primary endpoint was the percentage of wounds healed at 6 weeks between groups. At 12 weeks, the mean number of grafts used per healed wound for the dHACA group was 3. One adverse event and 1 serious adverse event occurred in the dHACA group; neither was graft related. Three adverse events and 1 serious adverse event occurred in the SOC group.

The drawbacks of this study included the lack of blinding patient and investigator and lack of a soft-tissue matrices comparator. Future studies may consider comparing different amniotic tissue forms and allowing wounds of greater severity or depth. In most instances, such high readings would have automatically caused a screen failure, and this might have resulted in a more biased population, which was why Doppler studies were performed on the entire cohort for evaluation of biphasic flow in the study extremities.

Finally, although the cost analysis was based upon publically available data mean sales price per cm 2 and published studies , a preferred, full health economic analysis of dHACA was beyond the scope of this trial. A draft assessment of wound care products prepared for AHRQ judged this randomized controlled study by DiDomenico, et al. In a retrospective cross-over study, these researchers evaluated the effectiveness of dHACA in those patients that failed to respond to the SOC treatments and who exited the original study after failing up to 12 weeks of SOC treatment. The primary end-point was the proportion of wounds completely healed at 12 weeks; secondary end-points included the difference in wound area from baseline to the end of study and the percentage area reduction PAR.

The mean wound area decreased from 1. The authors concluded that the results of this cross-over study supported the conclusions of the original RCT, which determined that aseptically processed dHACA was an effective means to treat recalcitrant DFUs. Moreover, they stated that further comparative investigations and studies of more complex wounds will further clarify which patients will most benefit from this technology. In addition, a comprehensive economic analysis was also beyond the scope of this study.

DiDomenico et al stated that amnion and chorion allografts have shown great promise in healing diabetic foot ulcers DFUs. Results from an interim analysis of 40 patients have demonstrated the accelerated healing ability of a novel aseptically processed, dehydrated human amnion and chorion allograft dHACA. Mean number of grafts used per healed wound during the same time period was 4.

These researchers stated that future trials of dHACA should consider a comparative arm using an advanced skin substitute for greater evidence and may even permit wounds of greater severity or depth. Additional clinical studies involving larger numbers of patients from a variety of clinical settings are necessary to establish the effectiveness and safety of AmnioBand. Glat et al noted that aseptically processed dHACA AmnioBand has shown great promise in the treatment of recalcitrant DFUs when compared with standard wound care but has not yet been compared to any other tissue forms used in treating DFUs.

The hypothesis was to conduct a randomized controlled trial RCT in which dHACA was compared to one of the earliest and most commonly accepted tissue-engineered skin substitutes TESS Apligraf in the treatment of non-healing DFUs over a period of 12 weeks to assess the superiority of healing. Following a 2-week screening period during which subjects with DFUs were treated with collagen alginate dressing, 60 subjects were randomized at 5 sites to receive either dHACA or TESS applied weekly, with weekly follow-up for up to 12 weeks.

The authors concluded that aseptically processed dHACA healed diabetic foot wounds more reliably, statistically significantly faster than and at significantly lower cost than TESS. The authors stated that study limitations included lack of principal investigator blinding, which was not possible due to visual dissimilarity of the tissues. Also, measuring the time to application was not performed. In addition, the recalcitrant nature of the wound in the location that the graft was applied was not looked at. Finally, withdrawing patients at 6 weeks rather than continuing through 12 weeks of treatment if their wounds were not sufficiently responding to treatment to ensure patient safety and permit other treatment pathways could be considered a limitation as well.

These researchers stated that future studies may consider looking at even more treatment algorithms that will further help enhance wound-healing technique in diabetic patients. AmnioAMP-MP Stratus BioSystems , a decellularized dehydrated human amniotic membrane DDHAM which is derived from the placental amnion and includes epithelial and stromal components that provide a collagen-rich extracellular matrix, cytokines, and growth factors.

The allograft, which is chorion free, provides a physical platform for infiltrating cells as well as extracellular proteins such as elastin, fibronectin, proteoglycans, glycosaminoglycans, and laminins, important in extracellular matrix strength, cell attraction, and migration. AmnioAMP-MP human amniotic extracellular matrix provides the scaffold for cell attachment and proliferation needed for granulation tissue development, vascularization, and epithelization for tissue repair with minimized inflammation and scarring.

Indications include, but not limited to, application to partial and full-thickness acute and chronic wound such as burns, diabetic wounds, venous wounds, arterial wounds, pressure wounds , including wounds with exposed tendon, muscle, and bone. AmnioAMP-MP delivers a natural collagen rich Type 1,11 extracellular matrix with extracellular proteins, including fibronectin and laminins, as well as cytokines and growth factors to damaged soft tissues. AmnioAMP-MP serves as a barrier to microbes and adhesions and as the structural platform to support appropriate cellular growth resulting in efficient healing with minimal inflammation and scarring. The actual size of the amniotic allograft that is applied is determined by the health care provider based on wound size.

AmnioCyte Plus Predictive Biotech is a minimally manipulated human tissue allograft derived from the extracellular matrix of the amniotic membrane. It is processed to preserve the cytokines, growth factors and scaffolding proteins from within the amniotic membrane matrix for homologous use. AmnioCyte Plus is intended for use in repair, reconstruction, replacement or supplementation of a recipient's cells or tissue by performing the same basic functions of amniotic membrane matrix in the recipient as it would in the donor. The amount and administration injected or topical of the allograft is determined by the clinician based on the intended use in each patient.

The product is distributed as a liquid allograft contained in a vial that is shipped frozen for preservation C on dry ice and is intended to be stored in that frozen state C to C or colder until used or expiration date is reached. It can be ordered in 3 vial sizes: 0. The product is simply drawn up after proper thawing using a 21GG needle to syringe and then prepared and applied.

Amnio-Maxx Royal Biologics is a dual layered, dehydrated, amniotic tissue membrane graft derived from Cesarean Section donors. The product is for wound covering, applied directly to the wound bed. Both products are used for chronic, non-healing wounds such as diabetic foot ulcers and venous leg ulcers or soft tissue defects. Amniotic tissue consists primarily of fibrillary and membranous collagens, elastin, and a mix cytokines and growth factors that provide the properties unique to placental tissues.

There are various sizes of each product; the provider uses the size that most closely matches the wound size. Once the graft has been applied, it is covered with a bandage. Amnio-Maxx and Amnio-Maxx-Lite both come in sterile pouches. There is a lack of evidence regarding the effectiveness of the Amnio-Maxx or Amnio-Maxx Lite allograft. AmnioPro Membrane Human Regenerative Technologies, LLC is a human amniotic tissue allograft consisting of dehydrated and decellularized human amniotic membrane that has been processed with proprietary HydraTek technology.

AmnioPro thin membrane is designed as a single layer wound covering for common wounds, and AmnioPro thick membrane is designed as a thicker single layer wound covering for deeper wounds where tissue bulk is required. It is intended to be used as a wound covering and is surgically applied to the skin in the treatment of chronic acute and surgical wounds. Both products are available in the following sizes: 1x1cm, 1x2cm, 2x2cm, 2x4cm, 4x4cm, 4x6cm, and 4x8cm. Amniorepair and AltiPly Zimmer Biomet are human cellular and tissue-based products. Each allograft is restricted to homologous use for use in procedures on a single occasion by a licensed physician.

The products are lyophilized placental membrane allografts that are aseptically processed to preserve the native extracellular matrix and endogenous proteins of the tissue. They are indicated for homologous use as a biological barrier or wound cover, forming a protective cover for a variety of acute and chronic wounds. The products are enclosed in a sterile wrap then sealed in a sterile inner and secondary outer pouch. The outer pouch is contained in a labeled box. Allograft size is indicated on the package label.

Using sterile forceps, the physician applies the graft directly onto the prepared wound bed with the stromal side directly against the wound bed. The graft absorbs the moisture directly from the wound bed; however, a few drops of sterile saline may be added to the graft after it has been applied to the wound if all areas are not rehydrated. The treated wound is covered with a non-adherent dressing followed by saline moistened gauze to fill but not pack the wound. There is a lack of evidence regarding the effectiveness of the AmnioShield amniotic tissue barrier.

Amniotext Regenative Labs is a minimally manipulated, amniotic membrane derived, human tissue allograft suspension product. It is intended to provide the extracellular matrix needed for the infiltration, attachment and proliferation of cells required for the repair of damaged tissue. Amniotic membrane human tissue-based products have shown to reduce scarring, fibrosis and adhesions in surgical and wound sites. It is administered through a syringe to the defect and the amount is determined by the clinician based on the size of the defect. Each human tissue-based product distributed by Regenative Labs is identified by its own unique serial number.

The product is packaged in a transport protective pouch. The product is contained in a cryogenic primary tissue container, which contains a product label that includes the product details such as unique product number, storage requirements and volumes. Contents are aseptically processed and are not considered sterile. Amniotext patches Regenative Labs are minimally manipulated, amniotic membrane-derived, human tissue allografts. The product serves as wound covering. It is typically used for chronic non-healing wounds such as diabetic foot ulcers and venous leg ulcers. It provides the extracellular matrix needed for the infiltration, attachment and proliferation of cells required for repair of damaged tissue.

The graft is applied directly to the wound bed and is available in various sizes, the size used matches the wound defect. The product is contained in a dual package tissue container system, in which the outermost ploy-foil pouch contains a product label that includes the product details such as unique product number, storage requirements and size. Contents are aseptically processed and sterilized, and are considered sterile. Amniofix MiMedx Group, Inc. Amniotic fluid contains fibrinolytic agents, and there is evidence from animal models of the potential for amniotic fluid injection for corneal wound healing and for prevention of adhesion formation following orthopedic surgery.

However, there is insufficient evidence from human studies to support the use of amniotic fluid injection for these indications. A controlled study is currently ongoing to evaluate the clinical effectiveness of AmnioFix in the reduction of the tenacity and frequency of soft tissue adhesions during the removal of segmental posterior lumbar instrumentation. In addition, a randomized controlled study of Amniofix in the treatment of recalcitrant plantar fasciitis is currently ongoing.

Acute wounds involving the dermal tissue layer may be appropriate for treatment with AnmioWrap2. AmnioWrap2 is provided dry in a double foil sterile pouch. It is available in various sizes, from 1 x 1 cm to 10 x 12 cm. Amniply International Tissue Inc. It comes in both a single and dual layer option. Amniply is a collagenous membrane derived from the submucosa of the placenta. The product serves multiple functions. It can be used in surgical procedures such as tendon repairs and spinal fusions. It can also be utilized as a wound covering for chronic, non-healing wounds such as diabetic foot ulcers, venous leg ulcer, and pressure ulcers. The graft is either placed into the wound bed or to the affected area. There are numerous sizes of Amniply.

The provider should always use the size that most closely matches the defect or wound. Each graft is individually packaged and can be stored in ambient temperature. Refrigeration is not required. In recent years, skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered human skin equivalents HSE. Apligraf graftskin Organogenesis, Canton, MA , also referred to human skin equivalent, is a living, cell-based, bilayered skin construct.

Like human skin, Apligraf has 2 primary layers, including an outer, epidermal layer made of living human keratinocytes, the most common cell type of the human epidermis, to replicate the structure of the human epidermis. The human keratinocytes and fibrobasts are derived from neonatal forsekins. The dermal layer of Apligraf consists of living human fibroblasts and bovine type 1 collagen, the most common cell type in the human dermis, to create a dermis-like structure that produces additional matrix proteins.

Proponents state that Apligraf stimulates the patient's own cells to regenerate tissue and heal the wound through mechanisms that include the secretion of growth factors, cytokines, and matrix proteins Snyder, et al. Apligraf does not contain melanocytes, Landgerhans' cells, macrophages, lymphocytes, or tissue structures such as blood vessels, hair follicles, and sweat glands. Rice et al used Medicare claims data to assess the real-world medical services utilization and associated costs of Medicare patients with diabetic foot ulcers DFUs treated with Apligraf or Dermagraft human fibroblast-derived dermal substitute HFDS compared with those receiving conventional care CC.

Medical resource use, lower-limb amputation rates, and total healthcare costs USD; from payer perspective during the 18 months following treatment initiation were compared among the resulting matched samples. Increased costs associated with outpatient service utilization relative to matched CC patients were offset by lower amputation rates This study is limited by the fact that it is based upon administrative claims data. The authors stated that its findings relied on accuracy of diagnosis and procedure codes contained in the claims data, and did not account for outcomes and costs beyond 18 months after treatment initiation. Apligraf was shown in clinical trials to heal even longstanding greater than 1 year's duration venous leg ulcers more effectively and faster than compression therapy alone.

The results of controlled, multi-center studies indicate that HSE interacts with the patient's own cells, responds to individual wound characteristics, and promotes healing. Further studies are underway to investigate its use for the treatment of pressure sores, dermatological surgery wounds and burns. At this time, there is insufficient information to extend coverage for the use of Apligraf in the treatment of these conditions.

Artelon poly[urethane urea] elastomer is a degradable biomaterial that serves as a scaffold for tissue ingrowth and provides temporary support for healing tissue. The effects of soft segment chemical composition and molar mass and the kind of diamine chain extender on the material properties were investigated. Nilsson et al stated that a new spacer for the trapezio-metacarpal joint TMC based on a biological and tissue-preserving concept for the treatment of TMC osteoarthritis OA has been evaluated.

The purpose was to combine a spacing effect with stabilization of the TMC joint. Artelon Artimplant AB, Sweden TMC Spacer is synthesized of a degradable polyurethaneurea Artelon , which has been shown to be biocompatible over time and currently is used in ligament augmentation procedures. Fibers of the polymer were woven into a T-shaped device in which the vertical portion separates the bone edges of the TMC joint and the horizontal portion stabilizes the joint. A total of 15 patients with disabling pain and isolated TMC OA were included in the study; 10 patients received the spacer device and the remaining 5 control group were treated with a trapezium resection arthroplasty with abductor pollicis longus APL stabilization.

The median ages of the 2 groups were 60 and 59 years, respectively. Pain, strength, stability, and range of motion were measured before and after surgery. Radiographical examination was performed in all patients before and after surgery. At follow-up evaluation 3 years after surgery, an unbiased observer evaluated all patients. Biopsy specimens were obtained from 1 patient 6 months after surgery. All patients were stable clinically without signs of synovitis. In both groups all patients were pain-free. The median values for both key pinch and tripod pinch increased compared with before surgery in the spacer group but not in the APL group. The biopsy examinations showed incorporation of the device in the surface of the adjacent bone and the surrounding connective tissue.

No signs of foreign-body reaction were seen. This was a small retrospective study; its findings need to be validated. Huss et al stated that full thickness skin wounds in humans heal with scars, but without regeneration of the dermis. A degradable PUUR, Artelon is already used to reinforce soft tissues in orthopedics, and for the treatment of osteoarthritis of the hand, wrist, and foot. These researchers performed in vitro experiments followed by in vivo studies to examine if the PUUR is biocompatible and usable as a template for dermal regeneration. Human dermal fibroblasts were cultured on discs of PUUR, with different macrostructures fibrous and porous. They adhered to and migrated into the scaffolds, and produced collagen. The implants were well-tolerated and increasing ingrowth of fibroblasts was seen over time in all subjects.

The fibroblasts stained immunohistochemically for procollagen and von Willebrand factor, indicating neocollagenesis and angiogenesis within the scaffolds. The authors concluded that PURR scaffold may be a suitable material to use as a template for dermal regeneration. Wojan et al conducted a Cochrane review to assess the effects of different surgical techniques, including Artelon joint resurfacing, for trapeziometacarpal thumb osteoarthritis.

The authors selected randomized controlled trials RCTs or quasi-RCTs where the intervention was surgery for people with thumb osteoarthritis. Outcomes were pain, physical function, quality of life, patient global assessment, adverse events, treatment failure or trapeziometacarpal joint imaging. We excluded trials that compared non-surgical interventions with surgery.

The authors used standard methodological procedures expected by the Cochrane Collaboration. Two review authors independently screened and included studies according to the inclusion criteria, assessed the risk of bias and extracted data, including adverse events. The authors included 11 studies with participants. Seven surgical procedures were identified Artelon joint resurfacing, trapeziectomy with ligament reconstruction and tendon interposition LRTI , trapeziectomy, trapeziectomy with ligament reconstruction, trapeziectomy with interpositional arthroplasty IA , arthrodesis and Swanson joint replacement. Most included studies had an unclear risk of most biases which raises doubt about the results. No procedure demonstrated any superiority over another in terms of pain, physical function, quality of life, patient global assessment, adverse events, treatment failure re-operation or trapeziometacarpal joint imaging.

One study demonstrated a difference in adverse events mild-moderate swelling between Artelon joint replacement and trapeziectomy with tendon interposition. However, the quality of evidence was very low due to a high risk of bias and imprecision of results. Low quality evidence suggests trapeziectomy with LRTI may not provide additional benefits or result in more adverse events over trapeziectomy alone. Mean pain three studies, participants was 26 mm on a 0 to mm VAS 0 is no pain for trapeziectomy alone, trapeziectomy with LRTI reduced pain by a mean of 2.

Mean physical function three studies, participants was Low quality evidence from four studies participants indicates that the mean number of adverse events was 10 per participants for trapeziectomy alone, and 19 events per participants for trapeziectomy with LRTI RR 1. Low quality evidence from one study 42 participants indicates that the mean scapho-metacarpal distance was 2.

None of the included trials reported global assessment, quality of life, and revision or re-operation rates. Low-quality evidence from two small studies 51 participants indicated that trapeziectomy with LRTI may not improve function or slow joint degeneration, or produce additional adverse events over trapeziectomy and ligament reconstruction. The authors stated that they are uncertain of the benefits or harms of other surgical techniques due to the mostly low quality evidence from single studies and the low reporting rates of key outcomes.

There was insufficient evidence to assess if trapeziectomy with LRTI had additional benefit over arthrodesis or trapeziectomy with IA. There was also insufficient evidence to assess if trapeziectomy with IA had any additional benefit over the Artelon joint implant, the Swanson joint replacement or trapeziectomy alone. The authors did not find any studies that compared any other combination of the other techniques mentioned above or any other techniques including a sham procedure. The authors concluded that they did not identify any studies that compared surgery to sham surgery and they excluded studies that compared surgery to non-operative treatments. They were unable to demonstrate that any technique confers a benefit over another technique in terms of pain and physical function.

Furthermore, the included studies were not of high enough quality to provide conclusive evidence that the compared techniques provided equivalent outcomes. Currently, there is insufficient evidence to support the use of Artelon for ACL reconstruction, rotator cuff repair, TMC osteoarthritis, and other indications. According to the manufacturer, ArthroFlex FlexGraft is a unique decellularized human skin allograft product indicated for the treatment of chronic wounds, such as diabetic foot ulcers and large surgical wounds. Arthroflex contains both collagen and elastin which provide structural support for resilience, a compliment of growth factors to assist healing, as well as multiple cytokines that assist in epithelialization and modulate the proliferation and differentiation of epithelium, and finally fully developed extracellular matrix which allows for infiltration of recipient cells.

The extracellular matrix stimulates epithelialization from the wound periphery and from remnant epidermal appendages when placed in contact with the wound. The manufacturer states that Arthroflex provides a physiological barrier that decreases water loss, electrolytes, proteins and heat from the wound bed and creates a mechanical barrier that reduces environmental microbiological contamination. Arthroflex is applied directly to the wound or ulcer and secured to the site in one of several ways, including the use of sutures, staples, or skin adhesive strips.

It is currently provided with a thickness of 1. The manufacturer states that they are likely to provide additional product sizes and thicknesses in the future. Arthroflex decellularized dermis patch has also been used in Achilles tendon repair and shoulder reconstruciton. Available peer-reviewed published medical literature on Arthroflex has focused on its biomechanical properties Ehsan et al, ; Beitzel et al, Mihata et al examined the clinical outcome and radiographic findings after arthroscopic superior capsule reconstruction ASCR for symptomatic irreparable rotator cuff tears. From to , a total of 24 shoulders in 23 consecutive patients mean age of These researchers used suture anchors to attach the graft medially to the glenoid superior tubercle and laterally to the greater tuberosity.

Physical examination, radiography, and magnetic resonance imaging MRI were performed before surgery; at 3, 6, and 12 months after surgery; and yearly thereafter. Average follow-up was Acromio-humeral distance AHD increased from 4. There were no cases of progression of osteoarthritis OA or rotator cuff muscle atrophy; 20 patients The authors concluded that ASCR restored superior gleno-humeral stability and function of the shoulder joint with irreparable rotator cuff tears. These researchers stated that these findings suggested that this reconstruction technique was a reliable and useful alternative treatment for irreparable rotator cuff tears.

Tokish and Beicker noted that chronic, massive, irreparable rotator cuff tears remain one of the most challenging pathologies in shoulder surgery to treat. Because of this, many treatment options exist for the management of chronic retracted rotator cuff tears; and SCR is one option that provides the potential to restore and rebalance the force couples necessary for dynamic shoulder function. These investigators described an all-arthroscopic technique using an acellular dermal allograft for SCR indicated for patients with a deficient superior rotator cuff.

This technique provided an option for patients with an irreparable rotator cuff tear without compromising future therapeutic options. The authors concluded that although this is a relatively new and unproven method for treating chronic irreparable rotator cuff tears, their short-term results were promising. Nevertheless, these researchers stated that larger studies with long-term follow-up are needed to fully evaluate the success of this technique. In a prospective, blinded, non-randomized, single-center, study, Gilot and colleagues compared the results of arthroscopic repair of large to massive rotator cuff tears RCTs with or without augmentation using an extracellular matrix ECM graft and to present ECM graft augmentation as a valuable surgical alternative used for biomechanical reinforcement in any RCT repair.

Subjects included patients who underwent arthroscopic repair of a large to massive RCT with or without augmentation with ECM graft. The primary outcome was assessed by the presence or absence of a re-tear of the previously repaired rotator cuff, as noted on ultrasound examination. The secondary outcomes were patient satisfaction evaluated pre-operatively and post-operatively using the item Short Form Health Survey, the American Shoulder and Elbow Surgeons shoulder outcome score, a VAS score, the Western Ontario Rotator Cuff index, and a shoulder activity level survey. These researchers enrolled 35 patients in the study: 20 in the ECM-augmented rotator cuff repair group and 15 in the control group.

The follow-up period ranged from 22 to 26 months, with a mean of The mean pain level decreased from 6. The American Shoulder and Elbow Surgeons score improved from The authors concluded that the use of ECM for augmentation of arthroscopic repairs of large to massive RCTs reduced the incidence of re-tears, improves patient outcome scores, and is a viable option during complicated cases in which a significant failure rate was anticipated. This study had several drawbacks. One such limitation was the study design; this was not a randomized study and included only 1 facility and 1 surgeon.

Moreover, these researchers did not comment on pre-operative MRI findings of fatty infiltration or atrophy. Finally, surgically, a non-controlled graft size could also be viewed as a limitation. Morris and colleagues noted that massive cuff tears can prove especially challenging to treat. Although these types of tears are often considered inoperable, augmented repair using an acellular dermal matrix may improve success rates. One acellular dermal matrix, AF-ADM, has shown encouraging results in an earlier case series which prompted this prospective study in an older population. After screening and evaluation for repair using traditional arthroscopic techniques, a total of 13 subjects with irreparable rotator cuff tears underwent a mini-open approach with AF-ADM augmentation.

An MRI was performed for each subject preoperatively, at 3 months post-operative, and at 12 months post-operative. Clinical outcomes were assessed at 3 months, 12 months, and 24 months post-operative using the Constant-Murley Shoulder Scoring Scale, the Modified ASES, and patient satisfaction scores. At 24 months follow-up, subjects demonstrated a significant Patient satisfaction was high at 24 months with a reported mean score of 3. There were no complications related to graft use.

Only 2 subjects exhibited radiographic graft failures with MRIs revealing tears in the native tissue but fully intact graft material. However, these subjects also showed excellent clinical outcome scores. The authors concluded that the assessments and patient satisfaction scores indicated that significant improvements can be achieved as early as 3 months with AF-ADM augmentation, despite the severity of these tears and age of the patients. The high success rate was especially notable as the subject group was older patients, who may have greater difficulty healing.

The results presented here showed that AF-ADM can be used successfully to treat massive and recurrent rotator cuff tears. The authors stated that one limitation of this study was the lack of a control group. Given the abundance of historical data from other studies using older or alternative techniques, these researchers felt that the documented radiographic and functional outcomes scores could be used by clinicians for comparison. However, this study does have the strength of a prospective study, and the subject population was similar enough to that of other studies to be comparable, yet different enough to add to the literature. However, potential bias was minimized by permitting only the clinician investigators to decide whether augmentation was necessary as well as to determine if repairs were successful.

In a multi-center study, Denard et al evaluated the short-term outcomes of arthroscopic SCR with dermal allograft for the treatment of irreparable massive rotator cuff tears MRCTs. The minimum follow-up was 1 year. Radiographs were used to evaluate the acromio-humeral interval AHI. A total of 59 patients with a mean age of Compared with pre-operative values, the VAS decreased from 5. The AHI was 6. These researchers stated that these preliminary results were encouraging in this difficult to manage patient population, but precise indications are important and graft healing is low in their initial experience.

Pennington et al presented the concept of superior capsular distance to quantitatively measure the decreased distance present upon restoration of superior capsular integrity. These investigators carried out a retrospective review of patients treated with arthroscopic SCR with a minimum month follow-up. Radiographic analysis of antero-posterior radiographs analyzed AHI and superior capsular distance. Digital dynamometric strength and functional ROM assessments were also obtained. The main inclusion criteria for patients in this analysis was all patients who underwent SCR during the time period of this report. A total of 86 patients with an average age of Outcome data revealed improvement in VAS 4.

Radiographic analysis showed increase in AHI mean 7. The authors concluded that this analysis revealed that arthroscopic SCR with acellular dermal allograft has been successful in decreasing pain and improving function in this patient subset. Radiographic analysis has also shown a consistent and lasting decrease in superior capsular distance and increase in AHI, indicating maintenance of superior capsular stability. Dimock et al stated that the short-term clinical results of SCR are promising, however, there is need for further long-term studies, as well as randomized controlled trials RCTs comparing SCR to other treatment modalities for irreparable rotator cuff tears.

These researchers stated that further imaging studies looking at graft healing rates are also needed as the healing rates published so far are variable. Additionally, the mechanism of action by which SCR delivered good short-term functional outcomes needs further clarification, as does the importance of the choice of graft type and thickness. Zastrow et al stated that preliminary results of SCR showed consistent improvement in shoulder functionality and pain reduction. However, a decrease in post-operative AHIs indicated dermal allograft elongation and persistent superior migration of the humerus, potentially contributing to later graft failure.

The authors stated that studies with longer follow-up are needed to evaluate the long-term utility of SCR in the treatment of irreparable rotator cuff tears. Makovicka et al stated that SCR is emerging as a viable surgical option to address the irreparable rotator cuff tear. Biomechanical studies suggested that the humeral head-stabilizing effect of SCR appeared to translate into improved clinical outcomes. The authors stated that future research should focus on further defining the indications, limitations, and optimal technique. Artiss Baxter Healthcare Corp. Artiss sets in approximately 60 seconds as opposed to rapid-setting fibrin sealants, which set in 5 to 10 seconds. This gives the physician additional time to position the skin graft over a burn before the graft starts to adhere to the skin.

The sealant is available in a pre-filled syringe frozen formulation and a lyophilized form. Both dosage forms, once prepared and ready to use, can be sprayed, thus enabling application in a thin and even layer. The multi-center, prospective, randomized, controlled study Foster et al, compared the use of Artiss to staples in burn patients requiring skin grafting. Wound closure at day 28 was assessed using test site planimetry and review of day 28 photographs by 3 independent blinded evaluators primary endpoint analysis. Investigator and patient-reported outcomes were also assessed.

The proportion of test sites with complete wound closure at day 28 was Blinded review of day 28 photographs confirmed that the rate of complete wound closure was similar between the 2 treatments, although the overall assessed rates of closure were lower than those determined by planimetry: Artiss The lower limit of the Therefore, Artiss is at least as efficacious as staples at the Complete wound closure by day 14 occurred in Artiss scored better than staples for all investigator-assessed outcomes e. Likewise, Artiss scored significantly better than staples for all patient-assessed outcomes e.

The safety profile of Artiss was excellent as indicated by the lack of any related serious adverse experiences. The authors concluded that Artiss is safe and effective for attachment of skin grafts with outcomes at least as good as or better than staple fixation. According to the manufacturer, Ascent combines a selected set of cells from amniotic fluid and their components, including TIMPs, growing factors, interleukins and hyaluronic acid.

Through complex interactions, these components work together to provide protecting, cushioning, lubrication, and inflammation reduction at the site of injury. Ascent is intended for the treatment of non-healing wounds and burn injuries. Ascent is offered in 7. The suggested reconstitution volumes are 0. Ascent is reconstituted using sterile saline based on recommended reconstitution amounts. Ferguson et al assessed scar improvement with avotermin recombinant, active, human TGFbeta3. In 3 double-blind, placebo-controlled studies, intra-dermal avotermin concentrations ranging from 0. Treatments avotermin and placebo or standard wound care were randomly allocated to wound sites by a computer generated randomization scheme, and within-participant controls compared avotermin versus placebo or standard wound care alone.

Primary endpoints were visual assessment of scar formation at 6 months and 12 months after wounding in 2 studies, and from week 6 to month 7 after wounding in the 3rd. Investigators, participants, and scar assessors were blinded to treatment. Efficacy analyses were intention-to-treat. In the 3rd study, avotermin significantly improved total scar scores at all concentrations versus placebo mean improvement: from Adverse events at wound sites were similar for avotermin and controls. Erythema and edema were more frequent with avotermin than with placebo, but were transient and deemed to be consistent with normal wound healing.

The authors concluded that avotermin has potential to provide an accelerated and permanent improvement in scarring. After preparation of the wound site, the human amnion allograft is surgically applied to the wound surface by the physician, extended beyond the wound margin and secured in place using the clinician's choice of fixation. AxoBioMembrane is available in 3 sizes; 1cm x 2cm, 2cm x 3cm, and 4cm x 4cm.

According to the manufacturer, Axoloti Biologix, INc. The products are available in 0. According to the manufacturer Axoloti Biologix, Inc. Axolotl DualGraft is a thicker version of the allograft for wound areas that are more vulnerable to damage. The product is available in four sizes; 1 x 2cm, 2 x 3cm, 4 x 4cm, and 4 x 6cm. According to HansBiomed Corp. BellCell HD is supplied as 1. Biobrane Mylan Laboratories, Inc. The fabric presents to the wound bed a complex 3-dimensional structure of tri-filament thread to which collagen has been chemically bound. Phillips et al reviewed applications of Biobrane on partial skin thickness burn wounds awaiting epithelialization.

After the patients had been evaluated and resuscitated as needed, the burn wounds were cleansed and debrided. Those evaluated as shallow were treated with Biobrane application. Joint surfaces were splinted for immobilization. The wound was inspected at 24 and 48 hours and if any fluid had accumulated it was aspirated and the wound was redressed. When the Biobrane was adherent, the wound was covered with a light dressing and joint immobilization was discontinued. Treatment with Biobrane dressing provided certain advantages over other topical wound care.

As the dressing changes were performed less frequently outpatient care was possible, with a resultant decrease in both the length of hospital stay and the ultimate cost of burn care. Wound desiccation is prevented and pain is decreased. Accurate diagnosis of wound depth is crucial if Biobrane is to be used. Very deep wounds will not allow Biobrane adherence, neither will it occur if the wound has a high bacterial count.

If joint surfaces are not splinted, the Biobrane will shear and not adhere to the wound. Convex and concave surfaces can be treated with Biobrane, which may need to be meshed. Bishop noted that Biobrane offers a number of advantages as a wound dressing for children. It does not require the use of surgical instruments, noisy distractions, painful manipulation of the wound, or regimented daily dressing changes. Biobrane does offer the pediatric patient with burns immediate comfort and protection, and enhances patient compliance and parental satisfaction. This is corroborated by the findings of Cassidy et al These researchers compared the effectiveness of Biobrane and Duoderm for the treatment of small intermediate thickness burns in children in a prospective, randomized fashion to determine their relative impact on wound healing, pain scores, and cost.

Data collected included mechanism of injury, time to complete healing, pain scores, and institutional cost of materials until healing was complete. No significant difference in time to healing or pain scores was detected between the 2 groups. The cost of each treatment was statistically more expensive in the Biobrane group. The results of this study showed that Duoderm and Biobrane provide equally effective treatment of partial thickness burns among in the pediatric population. Barret et al stated that partial-thickness burns in children have been treated for many years by daily, painful tubbing, washing, and cleansing of the burn wound, followed by topical application of anti-microbial creams.

Pain and impaired wound healing are the main problems. These investigators hypothesized that the treatment of 2nd-degree burns with Biobrane is superior to topical treatment. The rest of the routine clinical protocols were followed in both groups. Demographic data, wound healing time, length of hospital stay, pain assessments and pain medication requirements, and infection were analyzed and compared. Main outcome measures included pain, pain medication requirements, wound healing time, length of hospital stay, and infection. The application of Biobrane to partial-thickness burns proved to be superior to the topical treatment. Patients included in the biosynthetic temporary cover group presented with less pain and required less pain medication. Length of hospital stay and wound healing time were also significantly shorter in the Biobrane group.

None of the patients in either group presented with wound infection or needed skin autografting. Pain, pain medication requirements, wound healing time, and length of hospital stay are significantly reduced. Furthermore, in a review on tissue-engineered temporary wound coverings, Ehrenreich and Ruszczak stated that "[b]oth Biobrane and TransCyte have a strong body of evidence supporting their use in acute wounds. The most important clinical advantages of both products are prevention of wound desiccation, reduction in pain, reduced dressing changes, and in most reported studies, an acceleration in healing….

TransCyte may be justified in full thickness and deep partial thickness injuries, whereas Biobrane is more appropriate for more superficial wounds". Vloemans et al performed a systematic review of wound management and dressing materials to select the best treatment option for children with burns. A search in Medline and Embase revealed 51 articles for a critical appraisal.

The articles were divided into randomized controlled trials, cohort studies and a group of case-reports. Total appraisal did not differ much among the groups; the level of evidence was highest in the randomized controlled trials and lowest in the case-reports. The competitor dressing was Biobrane in six studies and amnion membrane in three. Tulle gauze, or tulle gauze impregnated with an antibacterial addition were the standard of care treatment in seven studies. The authors concluded that, in general, membranous dressings like Biobrane and amnion membrane performed better than the standard of care on epithelialization rate, length of hospital stay and pain for treatment of partial thickness burns in children.

However, hardly any of the studies investigated long-term results like scar formation. Austin et al reported on a five year retrospective cohort study evaluating upper extremity burns treated with temporary wound coverage Biobrane or cadaveric allograft. The primary outcome was to determine the impact choice of wound coverage had on operative time and cost. The secondary outcome was the need for revision of upper extremity debridement prior to definitive autografting.

The investigators included 45 patients in this study: 15 treated with cadaveric allograft and 30 treated with Biobrane skin substitute. The investigators found that Biobrane had a significantly lower procedure time Both techniques resulted in 2 revisions due to complications. The investigators concluded that Biobrane is superior to cadaveric allograft as a temporizing skin substitute in the acute burn wound, both in terms of procedure time and associated cost. The investigators stated that they believe that this is largely due to the relative ease of application of Biobrane. Krezdorn et al conducted a retrospective cohort study of adult patients that have been admitted with scalds in one center between and If describing every procedure would make the consent form too lengthy or detailed, FDA recommends providing the general procedures in the consent form with an addendum describing all study procedures.

It may be helpful to provide a chart outlining what happens at each visit to simplify the consent form and assist the subject in understanding what participation in the clinical investigation will involve. FDA believes that removing procedural details from the consent form will reduce its length, enhance its readability, and allow its focus to be on more important content, such as the risks and anticipated benefits, if any. The informed consent process must clearly describe the expected duration of the subject's participation in the clinical investigation see 21 CFR The subject must be informed of the procedures that will occur during such follow-up, which may be provided in a chart as described above. A description of any reasonably foreseeable risks or discomforts to the subject.

The informed consent process must describe the reasonably foreseeable risks or discomforts to the subject. This includes risks or discomforts of tests, interventions and procedures required by the protocol including standard medical procedures, exams and tests , especially those that carry significant risk of morbidity or mortality. Possible risks or discomforts due to changes to a subject's medical care e.

The explanation of potential risks of the test article and control, if any, and an assessment of the likelihood of these risks occurring should be based on information presented in the protocol, investigator's brochure, package labeling, and previous research reports. Reasonably foreseeable discomforts to the subject must also be described. For example, the consent form should disclose the severity and duration of pain from a surgical procedure or the discomfort of prolonged immobilization for MRI. All possible risks do not need to be described in detail in the informed consent form, especially if it could be overwhelming for subjects to read.

Information on risks that are more likely to occur and those that are serious should be included. The discussion may include information on whether a risk is reversible and the probability of the risk based on existing data. Information on what may be done to mitigate the most likely to occur and serious risks and discomforts should also be considered for inclusion. The description should not understate the probability and magnitude of the reasonably foreseeable risks and discomforts. If applicable, the consent document should include a description of the reasonably foreseeable risks not only to the subject, but also to "others" for example, radiation therapy where close proximity to subjects post procedure may be of some risk to others.

When appropriate, a statement must be included that the clinical investigation may involve currently unforeseeable risks to the subject or to the subject's embryo or fetus, if the subject is or may become pregnant. A description of any benefits to the subject or to others which may reasonably be expected from the research. The description of potential benefits should be clear, balanced, and based on reliable information to the extent such information is available. This element requires a description of the potential benefits not only to the subject for example, "This product is intended to decrease XXX; however, we cannot guarantee that you will benefit" , but also to "others" for example, "your participation in this research may not benefit you but may benefit future patients with your disease or condition".

Overly optimistic representations of the clinical investigation may be misleading and may violate FDA regulations that prohibit promotion of investigational drugs and devices see 21 CFR FDA considers payment to subjects for participation in clinical investigations to be compensation for expenses and inconveniences, not a benefit of participation in research. If payments are provided, the consent process should not identify them as benefits. Alternative Procedures or Treatments. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject. To enable an informed decision about taking part in a clinical investigation, consent forms must disclose appropriate alternatives to entering the clinical investigation, if any, that might be advantageous to the subject.

Prospective subjects must be informed of the care they would likely receive if they choose not to participate in the research. This includes alternatives such as approved therapies for the patient's condition, other forms of therapy e. Standard of care may include uses or treatment regimens that are not included in a product's approved labeling or, in the case of a medical device cleared under the k process, in the product's statement of intended uses. When disclosing appropriate alternative procedures or courses of treatment, FDA believes a description of any reasonably foreseeable risks or discomforts and potential benefits associated with these alternatives must be disclosed.

Where such descriptions or disclosures can contain quantified comparative estimates of risks and benefits e. The agency does not believe that imposing such a strict requirement for every case would be realistic or appropriate. It may be appropriate to refer the subject to a healthcare professional who can more fully discuss the alternatives, for example, when alternatives include various combinations of treatments such as radiation, surgery and chemotherapy for some cancers. This referral should be completed prior to the subject signing and dating the consent form. FDA recognizes that, while an individual subject may be eligible for more than one clinical investigation, that determination and the decision as to which trial would be most appropriate for a particular subject would need to be made on a case-by-case basis.

FDA believes that the discussion of other trials for which the subject may be eligible is best left to the informed consent discussion rather than the informed consent document and may need to include the subject's primary care provider. As applicable, the informed consent process should advise that participation in one clinical investigation may preclude an individual's eligibility to participate in other clinical investigations for the same or other indications. When there are multiple clinical investigations for evaluating the treatment of a particular disease, the sequence in which a subject may participate in the protocols may be important and should be discussed with the subject and the subject's primary care provider, if appropriate. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records.

The consent process must describe the extent to which confidentiality of records identifying subjects will be maintained 21 CFR FDA may inspect study records, for example, to assess investigator compliance with the study protocol and the validity of the data reported by the sponsor. See also 21 CFR FDA generally will not copy records that include the subject's name unless there is reason to believe the records do not represent the actual cases studied or results obtained. When FDA requires subject names, FDA will generally treat such information as confidential, but on rare occasions, FDA may be required to disclose this information to third parties, for example, to a court of law. Therefore, the consent process should not promise or imply absolute confidentiality by FDA.

Compensation and Medical Treatment in Event of Injury. For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained. For clinical investigations involving more than minimal risk, the informed consent process must describe any compensation and medical treatments available to subjects if injury occurs. Because available compensation and medical treatments may vary depending on the medical circumstances of the individual subject or the policies of the institution, the consent process should include an explanation to subjects of where they may obtain further information.

An example of an adequate statement is, "the sponsor has made plans to pay for medical costs related to research-related injuries" followed by an explanation of how to obtain further information. If no compensation is available, the consent process should include statements such as: An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject. The consent process must provide information on how to contact an appropriate individual for pertinent questions about the clinical investigation and the subjects' rights, and whom to contact in the event that a research-related injury to the subject occurs.

This information should include contact names or offices and their telephone numbers. FDA recommends that the individual or office named for questions about subjects' rights not be part of the investigational team. Subjects may be hesitant to report specific concerns or identify possible problems to someone who is part of the investigational team. In addition, the consent process should include information on whom to contact and what to do in the event of an emergency, including hour contact information, if appropriate. If contact information changes during the clinical investigation, then the new contact information must be provided to the subject.

This may be done through a variety of ways, for example, a card providing the relevant contact information for the clinical investigation. A statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled. This element requires that subjects be informed that they may decline to take part in the clinical investigation or may stop participation at any time without penalty or loss of benefits to which subjects are entitled.

Language that limits the subject's right to decline to participate or withdraw from the clinical investigation must not be used. If special procedures should be followed for the subject to withdraw from the clinical investigation, the consent process must outline and explain the procedures 21 CFR Also note that subjects may not withdraw data that was collected about them prior to their withdrawal, as discussed in Section V. I, Data Retention upon the Withdrawal of Subjects. The regulations identify additional elements of informed consent to be included, when appropriate. When appropriate, one or more of the following elements of information shall also be provided to each subject:.

The following elements are appropriate to provide to prospective subjects when the IRB determines the information is material to prospective subjects' decisions to participate:. A statement that the particular treatment or procedure may involve risks to the subject or to the embryo or fetus, if the subject is or may become pregnant which are currently unforeseeable. When appropriate, the consent process must contain a statement that the particular test article or procedure may involve risks to subjects or to the embryo or fetus, if the subject is or may become pregnant that are currently unforeseeable.

If long-term safety studies such as bench and animal testing are not completed, the informed consent process should explain that researchers have not completed studies that may identify potential risks, for example, carcinogenicity or teratogenicity. Involuntary Termination of Subject's Participation. Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent.

When appropriate, the consent process must inform the subject of anticipated circumstances under which the investigator may end the subject's participation without the subject's consent. Such circumstances may arise if, for example, the subject is unable to comply with procedures required by the clinical investigation, if the subject no longer meets the eligibility criteria for continuing in the study, or if the site withdraws from the study. If a subject is withdrawn from the study, the clinical investigator should explain to the subject the reasons for withdrawal, discuss other available treatment or research options, and, if appropriate, discuss plans to follow the subject after withdrawal for side effects.

Additional Costs to Subject. Any additional costs to the subject that may result from participation in the research. If subjects may incur additional expense because they are taking part in the clinical investigation, the consent process must explain the added costs. Subjects should be made aware that insurance or other reimbursement mechanisms might not fund the medical care they receive because they are participating in a clinical investigation even when the care is the standard care they would otherwise receive if not participating in a clinical investigation. Additionally, insurance or other forms of reimbursement might not pay for care related to complications or injuries arising from participation in a clinical investigation.

See also section III. If funds will be available to cover costs not covered by insurance or other forms of reimbursement, the consent form should describe how these funds will be made available to subjects or direct subjects on how to obtain further information. Because these issues may be complex, it may be appropriate to refer the subject to a knowledgeable financial counselor or reimbursement specialist to explain the costs and the insurance and reimbursement issues prior to signing the consent form.

Beyond the costs directly related to participation in the research, it may be appropriate to identify additional costs that the subject may incur, such as loss of income when the subject takes time off from work to participate in the clinical investigation and transportation costs. In some cases the cost of an investigational product may be charged to the subject. In clinical investigations involving investigational devices, the sponsor is permitted to recover the costs of research, development, manufacture, and handling of investigational devices see 21 CFR FDA may authorize sponsors in certain clinical investigations of drugs to recover the direct costs of making the investigational drug available, such as costs to manufacture, ship, and handle e.

Consequences of Subject's Decision to Withdraw. The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject. When appropriate, the consent process must describe the consequences of a subject's decision to withdraw from the clinical investigation and the procedures for orderly termination of participation by the subject. For example, when withdrawal from a clinical investigation may adversely affect the subject, the informed consent process must explain the withdrawal procedures that are recommended in order to ensure the subject's safety, and should specifically state why they are important to the subject's welfare. For some clinical investigations, an intervention should be withdrawn gradually or the investigator may recommend follow-up to ensure the subject's safety when an investigational intervention is prematurely terminated due to a subject's withdrawal.

In these cases, the consent process must explicitly inform the subject of the potential adverse effects of premature termination of the investigational intervention. If applicable, the consent process must explain whether a subject who withdraws early will receive future payments. Providing Significant New Findings to Subjects. A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject. The consent process must, when appropriate, include a statement that significant new findings that may relate to the subject's willingness to continue participation, such as new risk information, will be provided to the subject.

Significant new findings may include an unexpected adverse event or an adverse event occurring at greater frequency or severity than previously stated in the consent process. FDA encourages the inclusion of this statement in the consent form for clinical investigations where knowledge of risk is limited, for example, clinical investigations of the first use in humans, novel therapies, and new molecular entities, or complex clinical investigations that involve significant risk. The approximate number of subjects involved in the study.

The informed consent process must state the approximate number of subjects who will be involved in the clinical investigation, when appropriate. For example, a subject's decision may be influenced by knowledge that the clinical investigation is a small initial trial of the product such as a phase 1 or 2 drug clinical investigation or a device feasibility clinical investigation where only a small number of subjects participate.

When seeking informed consent for applicable clinical trials, as defined in 42 U. This will notify the clinical trial subject that clinical trial information has been or will be submitted for inclusion in the clinical trial registry databank under paragraph j of section of the Public Health Service Act. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results.

You can search this Web site at any time. All informed consent forms and processes for "applicable clinical trials" 26 initiated on or after March 7, , must contain the above quoted statement. Requirement for Written Documentation of Informed Consent. A copy shall be given to the person signing the form. When obtaining informed consent, informed consent must be documented by a signed and dated written consent form except under two specific circumstances, as described in FDA's regulations at 21 CFR When written informed consent is required, the use of electronic, including digital, signatures is permitted under FDA's regulations, provided it is in compliance with applicable regulations.

Additionally, the IRB may require the investigator to provide subjects with a written statement regarding the clinical investigation. FDA recommends that when an IRB waives the documentation requirement for informed consent in circumstances where there is minimal risk of harm as allowable under 21 CFR Alternative Methods of Obtaining Informed Consent. Traditionally, informed consent has been obtained in a face-to-face interview using paper consent forms. New technologies are becoming available that may serve as an alternative to the paper consent form in the informed consent process. Parties interested in pursuing alternative methods of obtaining informed consent are encouraged to contact FDA. Even in the context of paper consent forms, there may be certain circumstances when an alternative to a face-to-face consent interview may be appropriate.

For example, such an alternative may be appropriate when the subject or the subject's legally authorized representative is unable to visit the investigational site to sign the consent form, or if the screening procedures for the clinical investigation require prior activity, such as fasting, that requires consent but does not require a visit to the investigational site. When written informed consent is required, informed consent cannot be obtained solely by telephone. For studies involving no more than minimal risk, and no procedures for which written consent is normally required outside the research context, oral consent from a subject or a subject's legally authorized representative is permissible under 21 CFR When oral consent is used, FDA recommends that documentation of the process information provided, name of individual obtaining consent, date consent obtained be included in the study records see 21 CFR Methods other than a face-to-face consent interview may be acceptable if those methods allow for an adequate exchange of information and documentation, and a method to ensure that the signer of the consent form is the person who plans to enroll as a subject in the clinical investigation or is the legally authorized representative of the subject.

For example, the consent form may be sent to the subject or the subject's legally authorized representative by facsimile or e-mail, and the consent interview may then be conducted by telephone when the subject or subject's legally authorized representative can read the consent form during the discussion. After the consent discussion, the subject or the subject's legally authorized representative can sign and date the consent form and return the document to the clinical investigator by facsimile, scanning the consent form and returning it through a secure e-mail account, or by posting it to a secure internet address. The signed document should be filed with the subject's case history.

In addition, the person signing the consent form must receive a copy of the consent form 21 CFR Although FDA regulations do not require the subject's copy to be a signed copy, FDA recommends that a copy of the signed consent form be provided. In addition to signing the consent form, the subject or the subject's legally authorized representative must enter the date of signature on the form 21 CFR The person signing the consent form must receive a copy of the consent form 21 CFR This form may be read to the subject or the subject's legally authorized representative, but, in any event, the investigator shall give either the subject or the representative adequate opportunity to read it before it is signed.

When this method is used, there shall be a witness to the oral presentation. Also, the IRB shall approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness shall sign both the short form and a copy of the summary, and the person actually obtaining the consent shall sign a copy of the summary.

A copy of the summary shall be given to the subject or the representative in addition to a copy of the short form. The regulations provide for obtaining written informed consent by two different methods: a long form that embodies all the elements of informed consent see 21 CFR The long form embodies all the elements of informed consent as required under 21 CFR When the long form is used, a copy must be provided to the person signing the form, that is, the subject or the subject's legally authorized representative. An IRB may approve a short form to be used in appropriate situations where the elements of informed consent required by 21 CFR For example, IRBs may consider approving the use of a short form in situations where the subject or the subject's legally authorized representative is unable to read due to illiteracy or blindness see section V.

D, Physically Challenged Subjects. When the short form is used, the IRB is required to approve a written summary of the information to be presented orally. The information presented orally is to be the same quantity and quality of information as when a long form is used. Use of the short form requires that a witness be present to the oral presentation of information to the subject or the subject's legally authorized representative. FDA recommends that an impartial third party, not otherwise connected with the clinical investigation for example, clinical staff not involved in the research or a patient advocate , serve as the witness.

FDA recommends that the witness be present physically or by some other means, for example by phone or video conference during the entire consent process, not just the signing of the consent form. The purpose of the witness is generally to attest to the voluntariness of the subject's consent and the adequacy of the consent process by ensuring that the information was accurately conveyed and that the subject's questions were answered. The subject or the subject's legally authorized representative only signs and dates the short form. The witness must sign both the short form and the summary, and the person obtaining consent must sign the summary. IRBs, clinical investigators, and sponsors have responsibility for ensuring that the informed consent process is adequate and meets FDA's regulatory requirements.

The regulatory requirements represent the minimum information to be provided to potential subjects for informed consent. IRBs, sponsors, and investigators should consider providing additional information as appropriate. A critical part of this responsibility is for the IRB to ensure there is an adequate informed consent process that protects the rights and welfare of subjects participating in clinical investigations 21 CFR Review of All Informed Consent Materials.

IRBs must review all materials used in the informed consent process. The IRB's review is to ensure that information given to subjects as part of the consent process contains the elements identified in 21 CFR When reviewing clinical investigations, IRBs must ensure that the consent process minimizes the possibility of coercion and undue influence 21 CFR When a clinical investigation involves subjects who are likely to be vulnerable to coercion or undue influence, IRBs must determine that additional safeguards have been included in the clinical investigation to protect their rights and welfare.

For example, local circumstances may necessitate the inclusion of additional information relevant to the informed consent process for potential subjects from that particular community. HHS recommends that IRBs consider whether subjects should be informed of any financial relationships or interests that are associated with the clinical investigation, such as payments for services, equity interests or intellectual property rights. IRBs should determine whether subjects should be provided with information regarding the source of funding, funding arrangements, financial interests of parties involved in the clinical investigation, and any financial interest management techniques applied.

The IRB should consider the kind, amount and level of detail of information to be provided to subjects. The IRB has the authority and responsibility to require that information given to subjects as part of informed consent be in accordance with 21 CFR Investigators must use an IRB-approved written consent form when documenting informed consent, in accordance with 21 CFR Thus, the IRB should review the adequacy and appropriateness of all wording in the consent materials, as well as the overall length and presentation of information. Consent forms that are long, complex, legalistic, and have a high reading level 39 may overwhelm potential subjects and may inhibit reading of the full document and understanding of the relevant information.

The IRB should ensure that technical and scientific concepts and terms are explained, or common terms substituted, so that the anticipated subject population can understand all provided information 21 CFR IRBs may wish to evaluate, through subject interviews, how well the consent materials communicate critical information. Use of Standardized Language. IRBs should also address institutional requirements and applicable Federal, State, and local laws and regulations. Institutions may develop standard language or a standard format to use in portions of all consent forms for example, for those elements that deal with confidentiality, compensation, answers to questions, and the voluntary nature of participation to meet these requirements.

The investigator should advise the IRB of the consent process to be used. The materials and procedures used for subject recruitment, which typically include advertisements, must be reviewed by the IRB to ensure that these materials are appropriate. FDA considers this to include ensuring investigators allow sufficient time for subjects to consider the information, provide time and opportunity for the subjects to ask questions and have those questions answered, and allow time and opportunity for the subjects to consider fully whether to participate. The IRB must review all information given to subjects describing recruitment incentives, such as payments to reimburse potential subjects for expenses and inconveniences related to their participation 21 CFR In addition, the IRB must review the proposed amount and schedule of payments to subjects to ensure payments are appropriate to the time commitment and study procedures, and that subjects will not be unduly influenced by these incentives.

To approve a clinical investigation, the IRB must find that informed consent will be sought from each prospective subject or the subject's legally authorized representative and that informed consent will be appropriately documented. FDA recommends that the IRB inquire as to who will conduct the consent interview and what procedures will be followed. If procedures other than a face-to-face consent interview are proposed, such as by telephone, the IRB should consider whether the procedures will provide effective communication and accomplish the goals of the informed consent process. Alternative procedures may be of special concern when the clinical investigation involves complex procedures or when risks may be difficult to comprehend.

IRBs should consider using this authority when it believes it is appropriate 43 and will enhance the protection provided to subjects for example, when the investigator is also the treating physician for a potential subject, when the person conducting the consent interview is relatively inexperienced, or when the clinical investigation involves vulnerable subjects. In addition to observing a sample of consent interviews, the IRB could interview subjects to assess the consent process and evaluate the subjects' understanding of the clinical investigation. All information given to subjects as part of the consent process is to be reviewed and approved by the IRB 44 21 CFR During the clinical investigation, new information about the research or changes to the clinical investigation may arise that affect the rights or welfare of subjects.

FDA recommends that IRBs have procedures in place for the timely, efficient, and effective review of such new information or changes. When new information or changes in the clinical investigation require revisions of the consent form and any accompanying changes to the protocol , such revisions must be reviewed and approved by the IRB before the revisions are initiated, except when necessary to eliminate apparent immediate hazards to subjects.

Some changes may be reviewed and approved by expedited means, as provided for by 21 CFR For example, an IRB may decide expedited review is appropriate for changes to the consent form that reflect minor changes in the protocol or recruitment plan, such as new advertising for subjects following initiation of the clinical investigation when the advertisement incorporates wording from the approved consent form and the advertisement can be easily compared to the approved consent form. When expedited review is used, if the IRB reviewer is unsure whether the change qualifies for expedited review under 21 CFR If doubts persist as to whether the change qualifies for expedited review, then the change should be reviewed at a convened meeting of the IRB.

The IRB should ensure that there is a way to identify a revised consent form so that continued use of a previously approved version does not occur. While not required by FDA regulations, the use of date stamps is one possible mechanism for ensuring use of the most recently approved version of the consent form. The investigator can then photocopy the date-stamped consent form for use in the trial. The clinical investigator is responsible for protecting the rights, safety and welfare of subjects during a clinical investigation, and for ensuring that legally effective informed consent is obtained from each subject before that subject takes part in the clinical investigation see 21 CFR The clinical investigator should advise the IRB regarding the consent process, including who will conduct the consent interview.

Any information that will be given to subjects to review and discuss as part of informed consent must be submitted to the IRB for review and approval. An investigator may not begin the informed consent process with subjects until the IRB reviews and approves the clinical investigation, consent form, and the information to be given to subjects as part of the consent process. The clinical investigator's institution may have standard language or a standard format for consent forms for example, for those elements that deal with confidentiality, compensation, answers to questions, and the voluntary nature of participation.

FDA recognizes that investigators will also need to identify and meet such institutional requirements and incorporate them into the consent form for the IRB's initial review of the clinical investigation. When organizing the information in the consent form, FDA recommends that the clinical investigator consider the order in which the information is presented so that the elements most significant to the subject's decision to participate are presented first. The clinical investigator is also encouraged to incorporate any additional information of interest to subjects that may affect their rights and welfare.

For example, information about financial relationships and interests may be important to the subject see section IV. During the clinical investigation, the investigator may need to revise the consent form to address changes to the protocol or new information, such as significant new findings. The investigator will need to obtain IRB review and approval of the revised form. In addition, because the consent form is being modified to reflect changes to the protocol or new information, either of which may affect the willingness of already enrolled and actively participating subjects to continue in the clinical investigation, the IRB should determine the need to re-consent these enrolled subjects. To diminish confusion about the change, the investigator may use a prepared summary of the change to aid in an informative presentation to the enrolled subject.

However, this summary does not constitute the revised informed consent document. Delegation of Consent Interview. FDA regulations require that the investigator obtain or ensure that the legally effective informed consent of subjects is obtained. The individual obtaining informed consent should be knowledgeable about the clinical investigation and have the appropriate training and credentials; and the investigator should have a detailed plan for the supervision and oversight of the clinical investigation, including the informed consent process. The clinical investigator should consider whether information related to financial relationships or interests should be provided to subjects.

When there are financial relationships or interests, clinical investigators should consider the following actions:. Sponsors often provide clinical investigators with a model consent form that may be adapted by the clinical investigator to meet local needs. See section IV. The sponsor should promptly provide FDA's comments to the clinical investigator so that changes can be made to the consent forms. Because the clinical investigator must receive IRB approval before starting the clinical investigation see 21 CFR FDA recommends that the clinical investigator provide the sponsor with a copy of the consent form approved by the IRB.

For multicenter clinical investigations, minor changes may need to be made to the consent form to address local and institutional requirements. When IRB review results in substantive modifications to the consent form, i. Sponsors are not required to submit informed consent materials to FDA for all clinical investigations see, for example, 21 CFR FDA's regulations for drug including biologic and device investigations have different requirements for the submission of informed consent materials in applications see sections IV.

Generally, when informed consent materials are submitted, FDA reviewers assess the adequacy of the consent form by considering its communication of reasonably foreseeable safety issues and other elements required by 21 CFR In some situations, FDA may find a consent form to be misleading, inaccurate, or incomplete in a way that makes informed consent inadequate and noncompliant with 21 CFR part In these cases, FDA will require that specific revisions be made to address the concern s before the clinical investigation can proceed. FDA's review of the consent form does not substitute for the responsibility or authority of the IRB to review and approve the consent form and consent process as a condition for the clinical investigation to begin.

IRBs are responsible for ensuring the adequacy of the information in the consent form and may require modification as appropriate. Investigational New Drugs and Biologics However, if FDA determines that review of the consent form is necessary to make the determination of whether the clinical investigation may safely proceed, the Agency will request that the sponsor submit the consent form for review under 21 CFR As a general matter, the informed consent form will be reviewed for treatment INDs and treatment protocols 21 CFR part , subpart I and INDs conducted under the exception from informed consent requirements for emergency research 21 CFR For other clinical investigations, FDA often considers the following factors in determining whether to require submission and review of the consent form:.

After reviewing the consent materials, if the FDA review divisions have specific concerns about the adequacy or compliance of the consent materials with 21 CFR part 50, details about these concerns normally will be conveyed to the sponsor in writing. In rare circumstances, FDA may find a consent form to be misleading, inaccurate or incomplete in a way that makes informed consent inadequate and noncompliant with 21 CFR part 50 in such a manner as subjects would be exposed to an unreasonable and significant risk of illness or injury.

In these cases, FDA may require that specific revisions be made to address the concern s before the clinical investigation can proceed 21 CFR Investigational Medical Device s. For clinical investigations of medical devices for which an investigational device exemption IDE application is required to be submitted to FDA, the sponsor must include in the application copies of all forms and informational materials that will be provided to subjects to obtain informed consent.

After review, FDA may send the sponsor a letter citing deficiencies regarding the consent form. The clinical investigation may not begin until the sponsor has corrected these deficiencies. Sponsors and investigators may seek to review patient medical records for a variety of reasons related to a clinical investigation. Whether the record review is considered part of the clinical investigation, as defined under FDA's regulations at 21 CFR If the record review is part of the clinical investigation, then informed consent from the subject for the record review is required under 21 CFR part A survey of patient records at a site may be performed to determine whether the site has a sufficient number of patients with the condition of interest for the clinical investigation to be feasible.

Such a survey is in preparation for a clinical investigation and does not fall within the definition of a clinical investigation and, therefore, does not require informed consent under FDA's regulations. A patient's records may be reviewed to determine whether the patient is eligible for a clinical investigation. In order to facilitate this process, limited information about the potential subject may be recorded.

It should be noted, however, that only information to establish the patient's eligibility for the study and contact information should be recorded. This preliminary review of the patient's record and recording of limited information is considered preparation for a clinical investigation, does not fall within the definition of a clinical investigation, and does not require informed consent. Many institutions have privacy boards to help fulfill this function or they may give the IRB this responsibility.

Review by these entities may be required by the institution prior to these record review activities. If a patient's record does not include the basic information necessary to determine if he or she is eligible for the clinical investigation, additional information may need to be gathered from the potential subject. Obtaining informed consent may be required prior to obtaining the additional information. The records of a subject who was previously enrolled in a clinical investigation may be reviewed retrospectively, without reconsenting the subject, to collect additional information under certain limited circumstances, consistent with the original consent process.

If this retrospective review is to gather information that was intended to be collected but was missed that is, the protocol required collection of the information but it was not reported in the case report form and the purpose of the review is merely to fill in gaps in the record , then this review is considered to be covered by the previous informed consent obtained for the clinical investigation and further consent from the subject is not required. In cases where the additional information goes beyond what was identified in the original protocol and disclosed in the original consent form, obtaining informed consent for the additional information would be required.

Where possible, FDA recommends that the clinical investigator anticipate the need for obtaining further information and obtain consent as part of the initial consent process. In all of the above situations, there are privacy and patient confidentiality issues that need to be addressed. Individuals who do not understand English may ask or be asked to participate in a clinical trial in locations where English is the predominant language. The investigators and the IRBs that review such research should carefully consider the ethical ramifications of enrolling or excluding potential subjects when a language barrier may exist between the investigator s and some or all of the potential subjects.

Consistent with the requirement that selection of subjects be equitable 21 CFR When individuals who do not understand English are to be enrolled in a clinical study, IRBs and investigators must ensure that the information given to such prospective subjects or their legally authorized representatives is in language understandable to the subjects or their representatives 21 CFR Understandable means the information presented to potential subjects is in a language and at a level they can comprehend, including an explanation of scientific and medical terms.

The IRB must review and approve all English and non-English language versions of any consent documents long form or short form with written summary that are to be used by investigators to document the informed consent of subjects 21 CFR When reviewing proposed informed consent procedures involving translation of written and oral information that is to be presented to subjects, FDA recommends that the IRB review, and if appropriate, approve procedures for ensuring that the translations will be prepared by a qualified individual or entity.

A protocol amendment in which the investigator proposes to include use of translated informed consent documents for a study already approved by the IRB with English language consent documents may be considered no more than a minor change to the research and may qualify for an expedited review procedure under FDA regulations at 21 CFR FDA notes that informed consent should be viewed as an ongoing process throughout the course of a subject's involvement in the research. Therefore, FDA recommends that whenever subjects who do not understand English are involved in research, appropriate interpreter services be made available throughout the course of the research.

When investigators reasonably expect that the subject population for a proposed study will include individuals who do not understand English and can anticipate the specific language s that they will understand, the investigator should submit to the IRB, prior to its initial review, appropriately translated consent documents i. The investigators should also provide the IRB with a description of how interpreters for oral communication will be made available to subjects during the research. For example, if the investigators reasonably expect that the subject population for a proposed research protocol will include individuals who only understand Spanish and others who only understand Russian, the investigators should submit to the IRB, prior to its initial review, consent documents i.

FDA recognizes that investigators on occasion face circumstances where: 1 an individual who does not understand English is eligible for an IRB-approved research protocol; and 2 the investigator has an IRB-approved English language long form, but does not have an appropriate IRB-approved written translation of the long form, short form, or written summary. This may occur because neither the investigator nor the IRB reasonably expected enrollment of a subject for whom a translation would be needed.

For some research, the time frame for subject enrollment may provide sufficient time for the preparation and IRB review of an appropriately translated long form or an appropriately translated short form and written summary. When this is the case, translated consent forms are to be reviewed and approved by the IRB prior to enrollment of the subject. For other research, the timeframe for enrollment of a subject who does not understand English may not provide sufficient time for preparation and IRB review of appropriately translated consent documents. As a contingency for this situation, many IRBs have arranged for translation of a generic short form in multiple languages that satisfies the requirements of FDA regulations at 21 CFR In such circumstances, FDA considers procedures that include the following sequential steps to be one acceptable way of obtaining and documenting the informed consent of the subject:.

The investigator, in consultation with the IRB chairperson or another IRB member designated by the chairperson, hereafter referred to as designee whenever feasible, determines that there is sufficient justification e. In making a decision to allow enrollment of a subject who does not understand English into a research protocol without waiting for a written translation of the long form, the investigator and whenever feasible the IRB chairperson or designee should consider whether the consent process, under this circumstance, will provide the subject with sufficient opportunity to understand the information being presented.

If consent is sought and the investigator believes that the prospective subject has not understood the information presented, then the individual should not be enrolled in the research. In accordance with the requirements of 21 CFR As a prerequisite to using this procedure, the investigator must have available a short form written in a language understandable to the prospective subject and previously approved by the IRB 21 CFR To meet this prerequisite, the IRB or investigator must have arranged for translation of a generic short form into a language understandable by the prospective subject and the IRB must have approved the prospective use of such short forms for enrollment of subjects who do not understand English, as needed.

Additionally, the IRB must approve a written summary of what is to be said to the subject or the legally authorized representative. The IRB-approved long form can be used as this written summary. The procedure for obtaining and documenting the subject's informed consent with a translated short form and an English version of the long form, then includes the following:. This presentation may be an oral translation of the IRB-approved English version of the long form.

The oral presentation must be in language understandable to the subject 21 CFR The investigator, with the assistance of an interpreter if needed, answers any questions from the prospective subject. There must be a witness to the oral presentation who must not be the person obtaining informed consent 21 CFR Furthermore, the witness should be fluent in the language of the oral presentation. Note that when an interpreter assists the person obtaining consent, the interpreter may serve as the witness, but is not required to do so. After the subject has been enrolled in the research, the investigator takes the following additional actions:. The investigator promptly submits it to the IRB for review and approval.

FDA considers this step essential to the requirement that informed consent be documented by the use of a written consent document and that the subject be provided a copy 21 CFR Many of the clinical investigations regulated by FDA involve ongoing interventions and may involve long-term follow-up. FDA believes that translation of the long form is critically important as a means of providing subjects an ongoing source of information understandable to them. Although a competent person who does not read and write well can give informed consent and enroll in a clinical investigation, the sponsor, clinical investigator and IRB should consider whether any modifications to the informed consent process are necessary to ensure that the informed consent process is understandable.

For subjects with apparent low literacy, oral presentation of the information contained in the consent form is especially important. When the elements of informed consent are presented orally to the subject or the subject's legally authorized representative, the IRB may want to consider approving the use of a short form and written summary 21 CFR It should be noted that, even if the information is presented orally, the subject or the subject's legally authorized representative is required to sign the consent form whether the long form or short form is used unless the IRB has waived documentation of informed consent under 21 CFR Subjects who cannot write, can indicate their consent by "making their mark" on the consent form, when consistent with applicable State law.

In this situation, a progress note in the subject's case history should indicate the reason for the lack of a signature. A person who is physically challenged for example, physically unable to talk or write or has hearing or visual loss can enroll in a clinical investigation if competent and able to signal consent when consistent with applicable State law. The records relating to the clinical investigation must include documentation of the informed consent process 21 CFR FDA recommends that the subject's case history include a description of the specific means by which the prospective subject communicated agreement to take part in the clinical investigation and how questions were answered.

FDA recommends that investigators accommodate the specific needs of the study population. For example, the investigator could use an audio tape of the contents of the consent form or a form with enlarged font, depending on the level of impairment of the visually impaired subjects.