Center for documentary studies duke

Trying to figure out how many proficient English speakers there actually are here.

For anyone that got into Duke ED this application cycle, what’s included in the package? Just got accepted through a minority program and I’m very excited!

Hey, I just bought a second pair of Harman Kardon Soundsticks and I'm looking for a cheap speaker / soundbar good enough as a center channel speaker, any clue ? thanks !

Taking the SAT for the second time in June and want to study for it this time. I see some people recommend reading articles/books/papers. What will be the best, free place(s) to find articles/papers that are related to the different types of passages found in the reading section? Books are a hard no cause they take too much time and I will probably just give up in the middle of them. My plan rn is to read 2-3 articles/papers a day.
This is not the only thing I’m doing to study for EVBRW. I will do other things after all my AP exams.
Here is what I got on past EVBRW sections:
PSAT10: -7R -11W —> 660 PSAT: -6R -11W —> 670 SAT: -13R -13W —> 630
All three tests I got a 1240 composite on. Check my last post for the picture lmfao

Friday, March 24, 2023, Non Real Time Meeting
Friday, March 17, 2023, Non Real Time Meeting
Welcome to this non-real time meeting of codependency_12steps
Hi, I’m u/solid_jump_6828. I’m a recovered codependent and your leader for this meeting. Will those who wish, please join me in the Serenity Prayer: God grant me the serenity to accept the things I cannot change, courage to change the things I can, and wisdom to know the difference. Thy will, not mine, be done.
Strong sponsorship is necessary to live a recovered life. Sponsors are recovered codependents committed to living the Twelve Steps and Twelve Traditions to the best of their ability. Sponsors share their program up to the level of their experience and strengthen their recovery through this service to others. To find a sponsor, look for someone who has what you want and ask how he or she is achieving it. Will all sponsors please identify themselves in their post?
Suggested guidelines for sharing: As you share your experience and strength, please also share your hope. Please confine your sharing to your experience with the illness of codependency, the solution offered by the twelve steps and your own recovery from codependency, rather than just the events of the day or week. When responding to other member’s posts, please focus on your personal experience rather than advice giving. If you are having difficulties, share how you use the program to deal with them. If you need to talk more about your difficulties and seek solutions, we suggest you speak to your sponsor and other members after the meeting.
Share on how this paragraph relates to the illness of codependency and the solution offered by the Twelve Steps. Today we are studying the Big Book of Alcoholics Anonymous, Page 44 -45:
"If a mere code of morals or a better philosophy of life were sufficient to overcome alcoholism, many of us would have recovered long ago. But we found that such codes and philosophies did not save us, no matter how much we tried. We could wish to be moral, we could wish to be philosophically comforted, in fact, we could will these things with all our might, but the needed power wasn't there. Our human resources, as marshalled by the will, were not sufficient; they failed utterly."
Anonymous, Fourth Edition (p. 44-45). Alcoholics Anonymous World Services, Inc.
Closing: Freedom from codependency is possible by living a Twelve Step way of life. The *Big Book of Alcoholic Anonymous and a recovered sponsor are all you need to get started. Feel free to reach out by private message to newcomers, returning members, and each other. From the Big Book page 164: "Abandon yourself to God as you understand God. Admit your faults to Him and to your fellows. Clear away the wreckage of your past. Give freely of what you find and join us. We shall be with you in the Fellowship of the Spirit, and you will surely meet some of us as you trudge the Road of Happy Destiny. May God bless you and keep you- until then."
*Why the Big Book? Time and experience have proven it to be the most successful approach to the Steps no matter what the addictive problem may be (this includes codependency). We also know it to be the purest 12 Step document in existence. It worked for the founders of Twelve Step and it works for us today. If you don't have a copy of the Big Book you can access one for free: https://www.aa.org/the-big-book

Hi, so I have this issue. My mum has been making comments about my age since I turned 25, like sneak diss here and there to undermine my self esteem. My dad for the most part has been very nice to me. For the past couple of years I have been very depressed because of a SA experience I had and finally this year I have been getting better. I have been in the process of starting a career in mental health with children (starting soon) and volunteering for extra experience. But what I have dreamed of since I was a child has been art: specifically music, dance, performing. I was a bullied child and my parents emotionally neglected me and didn’t help when I was being abused. I didn’t flourish at all as a teen and was too shy to do any of these things. So for the past year I have been writing an album and a book (I studied English at Uni) and felt I needed to hone my skills. So I have been looking into starting lessons in ballet, gymnastics, singing and Muay Thai to fit into my artistic vision and be the best I can be. The dance/gym is to also help me feel strong and centred in my body after SA and depression making me inactive. It’s all been making me very very happy to enjoy a passion, something for me you know. So yesterday I was very excited (I would never dream of telling my parents about my love of performance and art the response would be brutal and they would call it cruelty to be kind) but I did tell him that I was starting gymnastics but obviously in an adult class. To which he said “it would be strange seeing an old, lumbering thing” I was shocked and said that was unkind to which he said well yeah in comparison to them. I quietly left and took care of my feelings upstairs. The next day he was very jovial a bit over the top tbh, but I decided to forget about the verbally abusive thing he said. I had had a great day one of the best, I woke up really early putting a wrench on my insomnia I’ve had since SA, productive and peaceful. I’m in bed this evening and he comes upstairs and we talk about my cat having dreams. I say “what do you think she is dreaming about” to which he says “being a little young cat I imagine.” I’m just shocked again, he deliberately took a stab at me again. Now, I am insecure about my age but more than anything I consider myself to be in my prime not to mention I look 10 years younger and have a graceful, agile body so this is all very strange to me like he wants me to put myself down. I’m so glad I never mentioned my artistic pursuits I do sing in the house sometimes and my mother has sneered at me and said it sounds shit (it doesn’t). So that’s why I hide a lot from them. I blocked him right after he said that and have been brainstorming boundaries. It’s funny because in February I blocked my mother because she was bullying me, he was kind then as I had a very bad panic attack but it seems I have to have the strength to fight his assaults on my confidence. I can’t move out for two reasons. In order to move to London I need more experience in the mental health field so working at this place for several months, not to mention I need the money, also one of my cats died two weeks ago( they are 20) and I don’t want to leave my little one alone just yet. I’m just very upset and shaken up and need to tell someone how I feel and hopefully feel reassured. I just want to be happy and reach my full potential, after all the horrors I have been through it’s what I deserve.

He also has played for the Seahawks, Bears and Giants. In his career, Jenkins has 212 tackles, 2. 5 sacks, four passes defensed, one forced fumble and one fumble recovery. Gonzalez, 27, has made 91-of-113 field goal attempts (80. 5 percent) in 63 games in his career. I’d say sophomore year, I understood, like, you gotta study this stuff, you gotta look at your plays, you gotta study your film. The team didn’t cut Gonzalez, though. Instead, the Panthers traded Gonzalez to the 49ers, his agent, Mike McCartney, announced. 49ers running back Christian McCaffrey, the PFT comeback player of the year, wanted a nice putter. Vikings receiver Justin Jefferson, the PFT offensive player of the year, wanted a gaming PC. Instead, the Panthers traded Gonzalez to the 49ers, his agent, Mike McCartney, announced. To me, there’s one thing about being cocky and that’s somebody that’s just talking, talking, talking. “You watch him on tape, you see the fire, the passion, the love for the game, that intrigues me about anybody. If you’re not doing it the way I’m telling you to do it, then you just not gonna play. ”Gardner-Johnson, prideful but eager to return to play, would later apologize. But Gardner-Johnson, confident in his ability, bet on himself and declared for the 2019 NFL Draft. AdvertisementDuring the pre-draft process, Gardner-Johnson met with all 32 teams. Jackson, in response to the league memo, tweeted, "Stop Lying that man never tried to negotiate for me. The Chicago Bears, on the other hand, were focused on defense, grabbing linebackers Tremaine Edmunds and T. J. Edwards. Howie Roseman, the PFT executive of the year. But some of the stuff, that’s just self-ingrained, it’s just in you, that’s just who you are. Register now!This site uses Akismet to reduce spam. He received a three-year, $21 million contract from the Minnesota Vikings, while Dalton Schultz got a one-year, $6. 25 million deal from the Houston Texans. Either way, Woods is turning 31 in April, and signing him to a two-year, $15. 25 million deal that includes $10 million total guaranteed was surprising. So he texted head coach Sean Payton with a request. “Coach, man, he’s dropping,” Glenn texted Payton. That sounds pretty pricy, but Pro Football Talk reports it's basically a two-year, fully guaranteed contract, where Hargrave will make up to $40. 75 million. - Alpha AI

So I admittedly have only recently started listening to Ali’s podcast in an effort to get a more holistic understanding of her, having previously only consumed her content on TikTok/IG so apologies in advance if I’ve missed something BUT:
Anyone else feel like Ali may be staying single on purpose for content? Here’s my theory and where it stemmed from:

• lately it sounds like there’s always an excuse for not going on another date. Is it possible that she’s just having a string of bad luck/has high standards? Sure. There is something to be said about having strict boundaries and values, and I can respect it, but it’s like there’s always something off. And I mean it’s men she’s dating so can we blame her lol jk (kinda) but still
• I think it’s general consensus that the most interesting and engaging content she has are centered around her dating - date GRWMs, date recaps, etc. and surely she knows this. Perhaps she’s thinking if she actually pursues a relationship successfully that her good content options will run dry. I think that many of us would argue that she actually could continue with interesting and relatable content through that process of navigating a new relationship but I’m not sure she would agree
• I would also argue that at this stage it’s going to take a really secure, chill man to be comfortable with dating Ali knowing her social media presence and content, and surely she knows this too. It may come down to her having to make a difficult decision or pivot in her content should she actually pursue someone seriously

I could be wrong, she also could just be in a certain place in her dating life, or subconsciously pushing people away for other reasons (not trying to diagnose her but I’ve certainly been there myself)
Anyway, just some thoughts/theories and would love to hear others’ input on this!

Hi, so I have this issue. My mum has been making comments about my age since I turned 25, like sneak diss here and there to undermine my self esteem. My dad for the most part has been very nice to me. For the past couple of years I have been very depressed because of a SA experience I had and finally this year I have been getting better. I have been in the process of starting a career in mental health with children (starting soon) and volunteering for extra experience. But what I have dreamed of since I was a child has been art: specifically music, dance, performing. I was a bullied child and my parents emotionally neglected me and didn’t help when I was being abused. I didn’t flourish at all as a teen and was too shy to do any of these things. So for the past year I have been writing an album and a book (I studied English at Uni) and felt I needed to hone my skills. So I have been looking into starting lessons in ballet, gymnastics, singing and Muay Thai to fit into my artistic vision and be the best I can be. The dance/gym is to also help me feel strong and centred in my body after SA and depression making me inactive. It’s all been making me very very happy to enjoy a passion, something for me you know. So yesterday I was very excited (I would never dream of telling my parents about my love of performance and art the response would be brutal and they would call it cruelty to be kind) but I did tell him that I was starting gymnastics but obviously in an adult class. To which he said “it would be strange seeing an old, lumbering thing” I was shocked and said that was unkind to which he said well yeah in comparison to them. I quietly left and took care of my feelings upstairs. The next day he was very jovial a bit over the top tbh, but I decided to forget about the verbally abusive thing he said. I had had a great day one of the best, I woke up really early putting a wrench on my insomnia I’ve had since SA, productive and peaceful. I’m in bed this evening and he comes upstairs and we talk about my cat having dreams. I say “what do you think she is dreaming about” to which he says “being a little young cat I imagine.” I’m just shocked again, he deliberately took a stab at me again. Now, I am insecure about my age but more than anything I consider myself to be in my prime not to mention I look 10 years younger and have a graceful, agile body so this is all very strange to me like he wants me to put myself down. I’m so glad I never mentioned my artistic pursuits I do sing in the house sometimes and my mother has sneered at me and said it sounds shit (it doesn’t). So that’s why I hide a lot from them. I blocked him right after he said that and have been brainstorming boundaries. It’s funny because in February I blocked my mother because she was bullying me, he was kind then as I had a very bad panic attack but it seems I have to have the strength to fight his assaults on my confidence. I can’t move out for two reasons. In order to move to London I need more experience in the mental health field so working at this place for several months, not to mention I need the money, also one of my cats died two weeks ago( they are 20) and I don’t want to leave my little one alone just yet. I’m just very upset and shaken up and need to tell someone how I feel and hopefully feel reassured. I just want to be happy and reach my full potential, after all the horrors I have been through it’s what I deserve.

Me (24F) and my boyfriend (23M) of 3 years has told me he wants to “end things” for the second time. We agreed on a break for now. But the first time this happened was in December where he told me he doesn’t feel connected to me, he’s losing feelings, and he doesn’t want to make any effort. After a 2 week long break, he reassured me that he was wrong, I made him a better person, etc. Well fast-forward, to March. Mind you I’ve been away for school for about two months, we’re texting every-day, FaceTiming, and watching movies. Communicating/distance is not an issue. We are very much affectionate & happy. The week just before I got back we got into an argument, it rubbed me the wrong way. When I returned home, we weren’t very happy with each-other. Shortly after that, he tells me the same things “I don’t feel connected to you” “Im self centered” “I’m losing feelings.” I’m reliving my nightmare. I love him very much, and I’ve invested so much, I want this to workout. I do feel conflicted, in regards to my well-being and protecting my heart.

For backstory, my roommates and I have been my friends for years. I've known person A since 2019 and his fiance by association since they got together. I let them move in with me back in September because they were homeless and didn't have anywhere to go. I only had a 1 bedroom apartment but i offered to split the livingroom in half for them to have privacy. We had agreed to split rent in 3 and I told them if it took a month or two to get on thier feet I'd be understanding. Additionally, until we were able to split the livingroom i offered to sleep there so they could have privacy in MY bedroom. That went on for about 3 months or so and all of a sudden they decided that half the livingroom wasn't enough they wanted to put up a door. I said no, because I wanted a mutual living space. I was out voted and told that I was being unrealistic bc the livingroom was too small. I came home from work one day to find they had put up a door and moved all of my shit into the bedroom WITHOUT MY CONSENT. This was in early decembelate November.
Then, they lost thier jobs back in about october shortly after thier car got repoed. I tried to be understanding, I even tried to help them find jobs i got person b a seasonal job with me temporarily and drove her to and from to try and help out. Person a went without a job until JANUARY, and person B's seasonal job ended after christmas. The only reason person A got his job was bc of our landlord helping him meanwhile neither of them have paid rent since October as they didn't have a job. They haven't helped with a SINGLE utility bill since they moved in. I've bent over backwards to help make sure they get to and from work, I let them use my car, I've lent them over 500 dollars(that they haven't paid back btw) just to try and help out because I knew they were struggling. At some point they decided that we were no longer splitting rent in 3 and instead in 2 because they are "a unit." You know, the rent they aren't paying for. Once person a got a new job he started paying back rent. Paid about 1k out of the 2.6k they owed. I got approved for rental assistance after about 3 months of waiting and now all of our back rent is paid and we're supposed to get refunded our back rent payments.
Neither person a nor b have a car still to this day. I drive person a to work every day for a whopping 10 dollars a week. (It's only a mile away but it's the opposite direction of my job and just in general annoying and not worth the 10 dollars when gas is over 3 dollars a gallon.) I let them use my car to go grocery shopping run errands literally anything they need i let them do it as long as I am not trying to do something else. I felt that was reasonable but i feel like they've just started to expect me to do everything for them. They get mad if I cant drive them somewhere and act like they have every right to use my car whenever they want.
Person b was supposed to start working at our seasonal job again today but we were scheduled for opposite shifts i was working til 330 and she was supposes to come in at 3 clearly i cant be in 2 places at once and i had somewhere to be at 4. There was no possible way I could drive her to work. When my manager told me last night she had to change the schedule and bring person b in for the evening shift i specifically said I can't take her then and that she had to uber. When she texted my roommate to let her know the schedule was changing and to confirm that was okay, I expected her to mention that I wouldn't be driving her, or for my roommate to ask me if she can get a ride. But she didnt ask me at all and then got pissed at me this morning when she texted asking me if I was working with her this afternoon and explained that i was working all morning and had somewhere to be. She then blew up on me and told me that I told her I can drive her friday- Sundays and that I should cancel my plans this afternoon to drive her to work which is bullshit bc she KNOWS how important these plans were to me. They are the only thing i do for myself and its not something im willing to sacrafice. Not for nothing these plans are reoccurring on a weekly basis at the same exact time so she knew I'd be busy.
Between both of my jobs I work 7 days a week. I'm exhausted and drained. And every time i try to help my roommates I feel like nothings ever good enough for them. Person b threw a shit fit this morning that im being "self centered" because I wasn't available to drive her. I told her that I might get off a little early and if I did I'd be able to come get her and take her in late, but that wasn't good enough for her. I recommended an Uber but she said she had no money left. Then I suggested that she asked our neighbor to drive her (to which I can't blame her for not wanting to do he's an asshole but imo it's better than nothing.) Then i said she can take my bike or walk the mile and a half she refused because it was raining and she didn't want to work in drenched clothes. When I moved into my apartment I had no car for like 2 months i saved every penny i was making to pay rent and buy a car. I rode my bike to and from work rain or shine because I needed the money and I didn't care. Was it fun? No. But as an adult it's my responsibility to get myself to work, not anyone else's.
Now I know I just ranted off a lot of bad things hut there's some good too. Generally they keep the house clean since they don't work (they complain that no one helps enough but they still do it), they dog sit if I need them too, and they can be nice people. I also typically enjoy their company when we aren't arguing. They help me if i need something from the store and vise versa as we all have food stamps. And overall they're still my friends despite all of this.
I do care about them but I'm at a point where I cant just let them walk all over me and take advantage of me either. I try really hard to avoid conflict and help them where I can but there comes a point where I have to put my foot down. This had been going on for months and I'm just tired of the poor treatment and the lack of respect. This was my home and they have me feeling like I can't even go there let alone live there. I feel uncomfortable in my own home and they only care when it affects them and tell me that I'm being selfish and I'm not "thinking of the group"
To top it all off our landlord sold our house and were stuck moving somewhere else, but everything wants us to make 3x the rent and I alone can't find an apartment that will allow my dog to come with me that will approve me based on my income. I'm stuck moving with them and finding a 2 bedroom house, because combined person a and I make enough to cover rent. I'm about to sign a 1 year lease with these people and I just need to know that I'm not being the asshole here. I'm just tired of them disrespecting me and my boundaries and for once I just want to stand up for myself.
TLDR my roommates are mad that I won't be thier taxi bc thier car got repoed and take advantage of my kindness and make me feel like an asshole for not being able to help them. I bend over backwards to help and nothings good enough.

Hey all, looking to pick up one of the two and not sure which might be better for pull rates. Looking at Pokémon Center ETB and the Dragonite VStar Box. Thanks for the help!!

Just wondering how long people studied for the NAPLEX after getting into a residency? Now that everything is winding down I want to study but I have my last rotation for 6 more weeks then graduation
Does anyone have tips on study schedule or if they can share their plan with us please?

“The Fallen Division.
Only the highest officers of the Terran military know about it. Fortunately, many quit upon coming to know about it. The force that the entire galaxy, even their own government, was getting worked up about was their own government?
Understandably, it troubled them. And the constant quitting would raise questions. So, sometimes, if they thought someone that quit would talk? The Fallen took care of them. A suicide for someone, perhaps turn blame of a murder to an enemy of that person or of the Terran Nations in general.
It wasn’t uncommon among those promoted high enough to need cover stories explaining why they quit. Of course this would raise some questions, some enemies, if this went public.
For example, why? What happened for this to be needed? Why were they always so emotionless about the atrocities this division committed? Every good soldier follows orders, but surely even the best question them? But these don’t falter, ever. Disturbingly mechanical yet so clearly alive. Even if their eyes always seem to be… Missing something. A soul, maybe. If you believe in that sort of thing. Perhaps it’s the lack of awareness of the emotions life once brought them. As if they didn’t recognize emotion or feeling at all. Not to mention that they don’t seem to even feel pain.
In this hearing, we will be discussing the galaxy’s new enemy. I am Militia General Aeryn Fisher with the former Terran Fleet Admiral, now your Commander, and my brother, Sam Fisher.”
The room had been silent, even before the General and Commander arrived. Everyone had heard what the hearing was about, and the tension had been as heavy as it was when the Fallen had been discovered. Complete silence reigned over the group as they waited for one of them to speak again.
They didn’t have to wait long, as the man on the right, now known as Commander Fisher, cleared his throat to grab their already hooked attention.
“Alright, so I figure most of you already knew that much about these Fallen. Yes? Good. Because this might get confusing.”
“As you hopefully guessed, this hearing is about the Fallen Division. And, as you already heard, I happen to have been high enough in rank to know about it, and to have had my hearings about them. As such, you could probably guess why I’m here.”
Commander took a moment, before a heavy sigh sounded from him. Anyone could tell he didn’t want to talk about this, though he knew he had to.
“The Fallen Division, as they’re now known, discovered something. Before they became what we know them as. They found something in the mind, something they claim is the reason the galaxy is irrational and war-hungry. According to them, they found a way to remove it, and, as extension, removed pain and their humanity.”
“Remember that when you fight them. They are not alive, and they will not stop until they are well and truly dead.”
“More importantly, they failed. You see, they didn’t remove it. The will they claim is their own is proof of this. They’ll tell you that yours is not your own, that we’re puppets to the force that they strive to kill. But you should not heed what they say.”
“They only amplified this “Darkness”, as they call it. Their own studies show that this force is what drives war and destruction, that harbors a hate for all life. In their attempts to destroy it, they’ve destroyed themselves and have given that life-eating disgust their bodies. You will not be hunting your fellow man or being, but a shadow of sapience out to slaughter the galaxy.”
“Do not hesitate to pull that trigger, or to obliterate their ships. Do not take any prisoners, for they won’t either. Surrender is not an option, they will not accept it and they will not offer it. Kill on sight.”
He casts his glare over the crowd, before the brothers exchange nods and he leaves. General Aeryn steps up, knowing they will undoubtedly have things to ask.
“Any questions?”
--------------------------
"Once you realize, life is disgraceful
It becomes easier to play the unfaithful
Disdain and pain cloud their minds,
Rage and stage bring back the binds
Call us mad, we’re simply free
From the righteousness of powers that be.
One day, you’ll die
So that they may learn
That you can’t deny
That which is unconcerned.
Writhing within your unstable minds,
An infection that devours sides
Once you realize, you don’t need pain
It becomes much easier, to contain."
-Fallen Division mantra
------------
Woo! It's such a fun setting, but I just can't write right now. No idea where I'd bring it past this, to be fair. I think I meant these as more for world building for a wider setting and short stories set within it, but I can't remember. Feel free to use, if you're interested in continuing it yourself.
Part 2

Hey all, looking to pick up one of the two and not sure which might be better for pull rates. Looking at Pokémon Center ETB and the Dragonite VStar Box. Thanks for the help!!

Hey there! I'm looking for a fandom/original romance, angst, etc centered roleplay! Discord is preferred, but I can write on here also. 18+ partners ONLY, as I am 22 years old and don't feel comfortable writing with minors.
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My name is Houston and I'm in CST timezone. I've been really wanting to write some some specific plots/genres which I will explain ^{_^} I am a more literate/novela writer, NO ONE LINERS OR ASTERIXS, and at least two paragraphs preferred [quality over quantity though] and I mostly write in Third Person POV. I'm looking for a plot with a MLM ship, though I can also do NBLM, NBLNB, or WLW/NBLW. I just prefer LGBT+ ships!
Fandoms I like to write [if wanting fandom RP] :
South Park(☆☆), The Last Of Us(☆), Hannibal, Ace Attorney, Better Call Saul/Breaking Bad, Top Gun, DCU(☆), JJBA, Golden Kamuy(☆), Yakuza Games(☆), Chainsaw Man, JJK, Tokyo Revengers(☆), Midnight Mass, Kickass(☆), Trigun, The Boys(☆☆), ETC!
[If there's any fandom specifically you wanna write, feel free to ask! I'm in a lot of fandoms!]
I am fine with writing most any characters, and fine with writing OCxOC, CCxCC, and OCxCC! We can write an original verse with specific genres or play OC(s) in a fandom verse! If you want to write as an OC, please have some kind of reference and information about them ^{_^}
Genres/plots I like to write :
ROMANCE(☆☆☆), Angst(☆☆), Whump (☆), Hurt/Comfort(☆), Hurt/No Comfort, Western(☆), Cyperpunk, Organized Crime(☆), Crime/mystery, Action/fighting(☆), Slice of life(depends), Etc!
I'm very versatile with my writings, so if there's any other ideas you may have, feel free to ask!
I enjoy writing various AUs and such, so if you have any plot ideas you've been wanting to write whether it be universe, fandom, genre/plots, I'm all ears! I am very friendly and love talking OOC and like making friends with my writing partners! ^{_^}
Extras/Misc : Writing samples are not required, but are a nice bonus! I am comfortable with writing many dark/gritty topics, but I will not write graphic SA or anything like that. It can be mentioned, but I will not write it.
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Thank you for reading and happy writings!! DM me if you're interested! ☆

Advanced cell and gene therapies for rare diseases have special drug development challenges including manufacturing and CMC– batch to batch variation since these deal with live cells – and limited initial clinical data, also this clinical data is often from surrogate endpoints.
The accelerated approval pathway is designed to address these issues by allowing approval based on surrogate and intermediate endpoints, provided confirmatory trials are completed within an agreed timeframe. However, recent audit of accelerated approvals of oncology drugs from last decade showed that many companies never completed the confirmatory trials. This has raised the bar for the agency and sponsors are getting some pushback on surrogate endpoints and are being imposed a requirement to start confirmatory trials before filing NDA/BLA (here). Unfortunately, the rare disease space with cell and gene therapies are seeing collateral damage in this controversy. But there is now some assurance that FDA is aware of special challenges that gene therapies face and is willing to address.
FDA’s Position on Gene therapies Accelerated Approval
Speaking at the 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, Peter Marks, director of the FDA's Center for Biologics Evaluation and Research (CBER), said that FDA understands the special clinical trial challenges for gene therapies in manufacturing, use of surrogate and intermediate endpoints, and a need for commercial viability – and FDA is willing to help:

• On manufacturing, he said, “manufacturing of these products is quite expensive and complicated; we need to address that.”
• On the use of accelerated approval pathway, he said, “to move [these products] through clinical trials in a relatively facile manner making use if what we have at our disposal at the agency which is things like the use of accelerated approval using surrogate endpoints like biomarkers or intermediate endpoints in order to get initial approval”
• On commercial viability, he said that besides reducing the cost of manufacturing, FDA can support market expansion by supporting regulatory expansion. He said, “[this can] potentially expand the market from US to global type of market we can help to get some type of regulatory conversion to not just be approved in the United States initially but to be approved in several different countries near-simultaneously. That may bring the market size to more commercial viability and not just one country benefit but everyone benefits and we will also benefit because other countries many have product that go ahead first that will come here sooner."

SOURCE

• Turning Gene Therapy Into Reality [Video]. By Peter Marks, MD, PhD. NeurologyLive. 20 March 2023 [archive]
• In the news: BioSpace, Reuters

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